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Launch of the Rome Statement for an HIV Cure
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Monday, 18 July, 2011 (Rome, Italy) -- Members of the Advisory Board for a global scientific strategy “Towards an HIV Cure” today launched the Rome Statement for an HIV Cure calling for an acceleration of HIV cure research. The announcement was made at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) currently being held in Rome.
Recent scientific advances in HIV research have led to a re-emergence of interest and optimism in prospects of at least a functional cure for HIV. The development of a functional cure which, without completely eliminating the virus from the body, would permanently suppress its replication and considerably diminish viral reservoirs, possibly leading to the long-term remission of patients.
Under the auspices of the International AIDS Society, a group of internationally recognized scientists and stakeholders is guiding the development of a global scientific strategy “Towards an HIV Cure”. The strategy aims at building a global consensus on the state of HIV reservoirs research and defining scientific priorities that need to be addressed by future research to tackle HIV persistence in patients undergoing antiretroviral therapy. The strategy will be presented at the XIX International AIDS Conference (AIDS 2012) which will be held in Washington DC from 22-27 July 2012. (1)
The International Scientific Working Group is co-chaired by Professor Françoise Barré-Sinoussi, IAS President-Elect and 2008 Nobel Laureate for Medicine, and Professor Steve Deeks, University of California, San Francisco (UCSF) and Positive Health Program (AIDS Program) at San Francisco General Hospital. The working group works closely with an advisory board composed of leading advocates and major research stakeholders in HIV cure, including representatives of people living with HIV and funders and clinicians from high prevalence settings. The Advisory Board is co-chaired by Prof. Barré-Sinoussi and Dr. Jack Whitescarver, Associate Director for AIDS Research and Director of the Office of AIDS Research at the National Institutes of Health.
“While there is certainly a high level of interest being expressed about finding a functional HIV cure (2), it can only be achieved through an increased and concerted international effort engaging not only the scientific community but all stakeholders involved in the HIV/AIDS response and global health,” said Professor Barré-Sinoussi.
“Partnership and collaboration are critical to the efforts to find an HIV cure,” said Dr. Whitescarver. “We need not only the finest minds but the very best in scientific alliances.”
Today’s Rome Statement for an HIV Cure lists the following three key objectives:
recognizing the importance of developing a safe, accessible and scalable HIV cure as a therapeutic and preventive strategy against HIV infection and to help control the AIDS epidemic.
committing to stimulating international and multidisciplinary research collaborations in the field of HIV cure research.
encouraging other stakeholders, international leaders and organizations to contribute to accelerating HIV cure research through their own initiatives and/or by endorsing this statement and supporting the alliance that the Advisory Board is building.
Board members, including co-chairs Professor Barré-Sinoussi and Dr. Whitescarver, have officially endorsed the statement.
Individuals and organisations wishing to sign the statement can do so by clicking here
Ends
Notes to Editors:
(1) For a complete list of Towards an HIV Cure Advisory Board and Working group members www.iasociety.org/Default.aspx?pageId=559
(2) Functional cure some HIV genetic material remains in the body, but the patient’s immune defence fully controls any viral rebound, allowing patients to be free of antiretroviral treatment; Sterilizing cure no HIV genetic material can be found in the body, HIV infection is eradicated. Given the nature of HIV - a retrovirus infecting the host immune system – and current knowledge and tools, a functional cure is more likely to be achieved.
About the signatories:
amfAR:
amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested nearly $325 million in its programs and has awarded grants to more than 2,000 research teams worldwide.
ANRS:
The Anrs (National Agency for Research on AIDS and Viral Hepatitis) is the leading organization for research on the HIV/AIDS and hepatitis epidemics in France, and a leader in the fight against these diseases in limited resource settings. In 2009, the Anrs had a budget of 44 million euros (62 million US dollars) from the French government, over 95% of which was allotted to research projects.
EATG:
EATG is a community organisation that promotes the interests of people living with HIV/AIDS. EATG’s mission is to achieve the fastest possible access to state of the art medical products, devices and diagnostic tests that prevent or treat HIV infection, and to improve the quality of life of people living with HIV/AIDS in Europe.
IAS:
The International AIDS Society (IAS) is the world's leading independent association of HIV professionals, with 16,000 members from 196 countries working at all levels of the global response to AIDS. Our members include researchers from all disciplines,
Clinicians, public health and community practitioners on the frontlines of the epidemic, as well as policy and programme planners. The IAS is the host of the IAS Conference on HIV Pathogenesis, Treatment and Prevention to be held in Rome July 17-20, 2011. The IAS is also the custodian of the biennial International AIDS Conference, which will be held in Washington D.C., USA, from 22 to 27 July 2012.
NIH:
The U.S. National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, behavioral and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. F
or more information about NIH and its programs, visit www.nih.gov.
Sidaction:
Sidaction, a France-based NGO, is a diverse coalition of individuals and organizations from France and from developing countries. Dedicated to fundraising, advocacy, and technical assistance to fight HIV/AIDS in France and in 29 low and middle income countries, Sidaction raises private funds to promote cutting-edge scientific research and to improve access to prevention, care, treatment, and support programs.
TAG:
The Treatment Action Group is an independent AIDS research and policy think tank fighting for better treatment, a vaccine, and a cure for AIDS. TAG works to ensure that all people with hiv receive lifesaving treatment, care, and information.
Further information:
In Rome: Onsite Media Centre Landline No. +39 0680241 756
International media:
Lindsey Rodger
lindsey.rodger@iasociety.org
Michael Kessler
mkessler@ya.com
+39 348 686 8417
Italian media:
Andrea Tomasini
tomasini39@hotmail.com
+39 329 263 4619
Restructuring NIAID’s HIV/AIDS Clinical Trials Networks
By Carl Dieffenbach, Ph.D., Director of the Division of AIDS, NIAID
Over the next several weeks, the National Institute of Allergy and Infectious Diseases (NIAID) will post a series of entries here on AIDS.gov related to planning for the future of NIAID’s HIV/AIDS clinical trial networks. The awards supporting the six current HIV/AIDS networks are set to expire in 2013 and 2014.
Building on the success of the current infrastructure, NIAID is looking to expand the scope of the network’s current activities to include the treatment and prevention of other infectious diseases of significance to people who are infected with HIV or are at risk for infection both domestically and globally, namely tuberculosis, hepatitis, and malaria. Additionally, we are looking for ways to increase collaboration across the networks, create transparent mechanisms for network leadership to solicit and support ideas from the research community, and develop a means for external researchers to tap into the clinical trial infrastructure and capacity that the network system provides. Finally, it is our goal to have each of the networks establish a means of designing and implementing a cross-network agenda to address research questions related to specific populations.
Each of our upcoming blog posts will focus on specific aspects of the network restructuring in which we are seeking input from the broader research and HIV/AIDS communities. Specifically, the entries will address:
NIAID’s clinical research priority areas, namely prevention, therapeutics and vaccines;
the structure of the new networks; and
the relationship between network leadership groups and clinical research sites.
The Future of the NIAID Clinical Trial Units
By Manizhe Payton, Director, Office of Clinical Oversight, Division of AIDS, National Institute of Allergy and Infectious Diseases
As the National Institute of Allergy and Infectious Diseases (NIAID) moves forward to restructure its HIV/AIDS Clinical Trials Networks and include a new network focused on infectious diseases other than AIDS, the Clinical Trial Units (CTUs) will continue to play a critical role in establishing, developing, and implementing the networks’ scientific research agendas. Additionally, we are seeking to strengthen the CTUs to enhance our ability to conduct clinical trials around the world.
CTUs provide the scientific and administrative expertise and infrastructure to implement the scientific agendas of the clinical research networks. Each CTU includes an administrative component with performance and resource management responsibilities and Clinical Research Sites (CRSs), the hospitals, outpatient clinics, health maintenance organizations, community health centers, private physician practices, and clinics where clinical trials are conducted. They provide uniquely identified and characterized potential cohorts (e.g., demographics, incidence and prevalence of HIV/AIDS) as well as qualified professionals with the facilities and resources necessary to conduct clinical research in accordance with Good Clinical Practices. Each CRS will be affiliated with one CTU and support the scientific agenda of one or more networks.
Although these enhanced CTUs will be similar to the existing structures, we anticipate supporting fewer CTUs that will generally be larger in size and scope compared to what we have today. Each CTU will need to affiliate with at least two HIV/AIDS Clinical Trials Networks and have the capacity and flexibility to work with other research networks. CTUs will also have the option of working with the new non-AIDS Infectious Diseases Clinical Trials Network, which will be focused on antimicrobial resistance and emerging infectious diseases.
CTU applicants interested in participating in the non-AIDS network will need to describe, in their applications, their capabilities, including potential investigators, participation in similar research efforts, and infrastructure. Because the exact research agenda for this network is not completely defined, CTU applicants will not need to identify specific performance sites and CRSs in their application. This statement of capability will be judged as either acceptable or unacceptable, rather than given a numerical score as in previous years.
The overall strength of the CTU will be judged in part by the strength of its CRSs, as well as its plan to efficiently coordinate and manage the sites’ activities. Further, we expect CTUs to take on greater responsibility for overall CRS evaluation and performance, in collaboration with the leadership groups for each of the networks for which each site is affiliated. To support greater flexibility to address evolving scientific agendas, CTU principal investigators and site leadership will play a major role in identifying and evaluating sites, including the performance and productivity of CRS pharmacy and laboratory components. For example, an investigator at the CTU level may propose an additional network affiliation to an existing CRS or add new protocol-specific sites to the CTU to meet specific network and/or NIAID research goals. To avoid redundancy and optimize efficiency, the CTUs, in collaboration with network leadership, will have more responsibility for evaluating the ability of specific sites to conduct study protocols, provide operational support to the sites, and drive quality management processes.
Successful collaboration between the network leadership groups and the CTUs will also require transparency in financial and operational matters. For example, the CTUs will have increased responsibility for efficient resource utilization, including reallocation of resources as necessary. The CTUs will also have a substantial coordinating role in administration and resource management (financial, human, technical and clinical) for their individual units and the sites.
Partnerships will also continue to be an essential component of the NIAID clinical trials enterprise. To that end, NIAID remains committed to preserving and strengthening relationships with the communities where we conduct research through community advisory boards. To encourage new scientific research collaborations, NIAID will build a mechanism for allowing other partners (e.g., other NIH Institutes and U.S. Government agencies) to access the CTU infrastructure.
Enabling others to tap into our expansive clinical trial network will build efficiencies into the clinical trials process by helping to meet enrollment targets faster. Similarly, granting access to network resources, such as data management, regulatory and statistical expertise, and clinical monitoring capabilities will also help achieve mutual clinical research goals.
Overall, we believe that these changes will enable the CTUs to provide greater breadth in scientific expertise and capability, increased capacity, and greater flexibility in addressing scientific agendas of the newly awarded clinical trials networks. We welcome your thoughts and feedback.
Looking Ahead: NIAID’s Future HIV/AIDS Therapeutics Priorities
By Carl Dieffenbach, Ph.D., Director of the Division of AIDS, NIAID
Since the 1980s when the HIV/AIDS epidemic was first recognized, NIAID-supported clinical research has helped to save millions of lives and played a key role in defining the standard of care for treating HIV infection. This blog post describes what we are seeking for the next wave of HIV/AIDS therapeutic approaches. Specifically, we have identified the following three research priorities: 1) finding a cure for HIV-infected individuals; 2) developing therapeutic strategies for preventing and treating tuberculosis (TB) and hepatitis C in HIV-infected individuals and individuals at high risk for co- infection; and 3) addressing the long-term consequences of treatment of HIV infection.
A cure for HIV/AIDS would have a significant impact on the global burden of HIV/AIDS by reducing HIV prevalence and providing increased hope for controlling and ultimately ending the pandemic. Current antiretroviral therapy (ART) used to treat HIV infection suppresses the virus’ ability to replicate but does not eliminate the hiding spots in the body where the virus lays dormant (called “reservoirs”). We define a “cure” for HIV-infected people as permanent remission of disease in the absence of therapy. Currently, we are investigating two distinct approaches toward this type of cure: identifying each of the HIV reservoirs and finding ways to eliminate them; and maintaining and/or boosting the immune system, so that it can control HIV replication on its own when ART is discontinued. Evaluating both approaches will require innovative and rigorous clinical research. Additionally, specialized laboratories will be needed to measure a variety of parameters, such as reservoir size, the low levels of virus that continue to persist, and anti-HIV immunity. These clinical activities will need to be closely linked with existing efforts to discover and develop strategies for a cure.
Until there is a cure for HIV infection it is critical that we continue to develop strategies for preventing, diagnosing and treating infectious diseases commonly associated with HIV, such as TB, which is the leading cause of death in persons with HIV/AIDS. Our TB research agenda will include the development of new regimens for prevention and treatment. The goal is to have treatment regimens that are effective, well-tolerated and shorter in duration, that do not interfere with the effectiveness of ART, and that target drug-sensitive and resistant TB, including extensively drug resistant TB. Discovery and careful assessment of improved diagnostics, drug-sensitivity testing, and biomarkers for predicting disease progression and therapeutic responses are priorities since TB manifests itself in different ways in HIV/AIDS patients and is much more difficult to diagnose than in people without HIV infection.[b]Co-infection with HIV and hepatitis C virus is another area of major concern. Current therapies for hepatitis C are often poorly tolerated and are not effective against all subtypes of the virus. At least seven new treatments are in development for hepatitis C infection, and we hope that some of these will lead to safer and more effective regimens for people infected with both HIV and hepatitis C virus. In addition to new treatments, there is a great need for new hepatitis C diagnostic tools, including detection of proteins in blood that predict treatment success or failure.To further our discussion on the future directions of therapeutics research, please consider the following:
Are the three priority areas that we have identified for HIV/AIDS therapeutics research the appropriate priorities?
What is the best way to link the discovery and clinical evaluation of possible cures for HIV/AIDS?
Are we defining an HIV/AIDS “cure” appropriately?
On what areas of TB and hepatitis C clinical research should NIAID focus? Are there other infectious agents that deserve priority efforts?
What are the most important non-infectious co-morbidities associated with HIV infection that NIAID should address in its research agenda?
Can earlier initiation of antiretroviral therapy for HIV infection prevent some of the premature aging and other co-morbidities associated with treated HIV disease, or are other targeted therapeutic approaches required?
What is the best approach for advancing HIV, TB, and hepatitis C biomarker research?
For both TB and hepatitis C, significant research efforts are supported by several public and private sector funders, including other divisions within NIAID. These areas of the therapeutics agenda need to be coordinated with existing research efforts to facilitate more efficient clinical research planning and highly productive collaborations.
Effective therapy for HIV infection has been available for about 15 years. During this time, antiretroviral drugs have become safer and easier to take. However, we still do not fully understand the consequences of long-term treatment of HIV infection, especially the mechanisms driving residual inflammation. A major concern is the increased rates of certain conditions experienced by HIV-infected individuals who have been infected for long periods of time, even those whose viral load has been adequately suppressed with ARV therapy. These include the onset of early aging characteristics, cardiovascular disease, insulin resistance, non-AIDS-associated cancers and kidney disease. Basic and clinical research are needed to define the underlying mechanisms of these conditions and develop therapeutic strategies to target these mechanisms. The key to developing novel therapeutic strategies will involve both the investigation of biomarkers and the evaluation of novel HIV therapies.
We welcome your thoughts and feedback on these issues. It has been interesting to see the responses to our two previous blog postings, and I hope you will continue to comment.
In the next blog posting, we will examine the direction of NIAID’s HIV vaccine clinical research priorities.
The National AIDS Strategy at One Year
By Jeffrey S. Crowley, M.P.H., Director, Office of National AIDS Policy (Cross-posted from White House Office of National AIDS Policy Blog)
It’s been one year since we launched the first comprehensive National HIV/AIDS Strategy and today we are releasing an implementation update to keep you up to speed on the latest work. We plan to release a more comprehensive progress report after the conclusion of the calendar year, but as we mark this critical first year, we wanted to provide some reflections on key first-year achievements.
The Strategy details President Obama’s three goals: 1) reduce the number of new HIV infections, 2) increase access to care and improve health outcomes for people living with HIV, and 3) reduce HIV-related health disparities. Our mission is for the United States to become a place where new HIV infections are rare and when they do occur, every person, regardless of age, gender, race/ethnicity, sexual orientation, gender identity or socio-economic circumstance, will have unfettered access to high quality, life-extending care, free from stigma and discrimination. As you will see from the report, agencies throughout government are stepping up to the plate and stakeholders from all sectors are taking action.
Ultimately, for the Strategy to be truly successful, we need you. The Strategy isn’t about what government can do alone. We know that businesses, the faith community, and all sectors have a role to play. The video above features everyday leaders implementing the strategy in their own communities. We hope that you can use this to engage more people in our collective efforts to implement the Strategy and energize key partners to continue their efforts.
Reflections on the One-Year Anniversary of the National HIV/AIDS Strategy Launch
By Howard K. Koh, M.D., M.P.H., Assistant Secretary for Health, U.S. Department of Health and Human Services
Dr. Howard Koh
Since President Obama released the first-ever National HIV/AIDS Strategy (the “Strategy”) last July, 2010, I have had the privilege of helping to guide its implementation as well as coordinate the many integrated federal activities involved in reaching these ambitious goals. On this first anniversary, we can celebrate considerable strides toward reaching the Strategy’s clear and measurable targets by 2015, but there is still more work to be done across all sectors.
The comprehensive Strategy serves as a roadmap for reinvigorated governmental and non-governmental partners across the nation. I am encouraged by the efforts underway in states, cities and communities to integrate and refocus existing HIV prevention, care and treatment efforts to deliver better results. A major example of dedicated, improved coordination is the HHS-supported 12 Cities Project which is focused on areas in the U.S. that bear the highest AIDS burden. In addition, a broad range of community-based organizations, academic institutions, businesses and faith communities are aligning their efforts toward the shared goals and unprecedented opportunities presented by the Strategy.
I am also heartened by the heightened levels of communication and coordination on existing and new HIV/AIDS activities within the Department of Health and Human Services as well as cross-agency collaboration among our federal partners at the Departments of Housing and Urban Development, Justice, Labor, Veterans Affairs and the Social Security Administration. In addition to increasing coordination of HIV programs, we have also developed better ways to monitor and report on our collective progress. This integrated approach is essential to move the country forward and accomplish the Strategy’s vision of a nation where new HIV infections are rare and where every person will have quality, life-extending care.
We have also woven the Strategy into other key national health initiatives. The Affordable Care Act (ACA) is already improving access to health insurance coverage for people living with HIV/AIDS, ensuring quality coverage and increasing opportunities for health and well-being. The landmark law makes considerable strides in improving care and advancing equality for people living with HIV and AIDS. For details, read “How Does the Affordable Care Act Impact People Living with HIV/AIDS?”
Furthermore, we are coordinating and aligning our HIV prevention, care and treatment efforts with complementary Department-wide and government-wide prevention and care initiatives including the HHS Action Plan to Reduce Racial and Ethnic Health Disparities, Action Plan for the Prevention Care and Treatment of Viral Hepatitis and National Prevention and Health Promotion Strategy.
Although we have more work ahead of us, we have made tremendous progress this last year at HHS, across the federal government and in partnership with states and communities. Reaching these goals and realizing our vision requires sustaining the great momentum of this first year across all levels of government, the private sector and with the leadership of people living with HIV and affected communities.
It’s an honor to be a part of this historic process with so many committed partners that believe in a common purpose. I look forward to continuing our important work to make the Strategy come alive and leave a legacy for America.
When to Start Antiretroviral Therapy (Pts coinfected with HIV and HCV should be a strong segment to try the HP. Apparently the govt. is refocusing on HIV mgmt in the US)
Clinical Infectious Diseases
Wilkin TJ et al. - Data suggest that the strategy of earlier initiation of ART is cost-effective and efficient. Consequently, many antiretroviral guidelines from around the world now recommend routine initiation of ART when the CD4 cell count decreases to <350 cells/muL or at higher CD4 cell counts for certain subgroups of HIV-infected individuals, such as pregnant and/or breast-feeding women and persons with HIV-related nephropathy or hepatitis virus coinfection.
A Sustained Virologic Response Reduces Risk of All-Cause Mortality in Patients With Hepatitis C
Clinical Gastroenterology and Hepatology , 07/16/2011
Backus LI et al. - An sustained virologic response (SVR) reduced mortality among patients infected with hepatitis C virus (HCV) of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities.
Results
HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively.
Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died.
In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype.
Aethlon Medical Releases Shareholder Letter
To our Shareholders:
Last December, I authored a shareholder letter which referenced the viewpoint of healthcare leaders who felt a need for innovative new therapeutic strategies to evolve as escalating regulatory costs, challenges and uncertainties made it nearly impossible for small to mid-size organizations to commercialize their drug candidates. In response, we introduced the Aethlon ADAPT™ (Adaptive Dialysis-Like Affinity Platform Technology) system, as an innovative medical device platform that provides a basis to create new therapeutic devices through the convergence of affinity drug agents and plasma membrane technologies. The Aethlon ADAPT™ system provides a previously unrecognized commercialization pathway to antibody and other affinity drug developers, who should also appreciate a less onerous medical device regulatory pathway. We are already seeing evidence of our ADAPT™ system being the impetus for industry collaborations that offer new channels of early revenue generation.
On May 25th, we introduced our Aethlon ADAPT™ system to the drug industry at the C21 Life Sciences Partnering Conference. However, we had already begun to leverage our ADAPT™ system on April 1st, through a response to a government contract opportunity offered by the Defense Advanced Research Projects Agency (DARPA) entitled, "Dialysis-Like Therapeutics." Included within our response was a proposal to develop a device that would reduce the incidence of sepsis in wounded war-fighters. I am pleased to inform you that our submitted program was chosen for funding by a panel of experts assembled by DARPA. While it is an honor to be chosen to receive a contract award, I ask that you curb any assumption that we have won a contract based on information that may be published on the Internet. A contract that leads to funding of our proposed program is predicated on the successful completion of a detailed contracting process. On June 29th, we again leveraged the capabilities of our ADAPT™ system through a response to a U.S. Army initiative to create a device that would meet the objective of a program entitled "Blood Purification for Organ Failure."
The genesis of the Aethlon ADAPT™ system is our Hemopurifier®, a device that has demonstrated broad-spectrum activity against infectious viral pathogens, immunosuppressive proteins and exosomes secreted by cancer. Increasingly, exosomes are being discovered to have implications in other life-threatening diseases. Next Tuesday (July 19th), we will meet with FDA officials to discuss a proposed clinical program to support the regulatory advancement of our Hemopurifier® as a treatment countermeasure against bioterror and pandemic threats. Based on data collected from clinical programs conducted in India, we will also seek permission from the FDA to expand our treatment indications to include Hepatitis C virus (HCV). Formal FDA feedback to next week's meeting would likely occur in early fall. Should the FDA grant permission to initiate our U.S. clinical studies, we have already submitted (on May 31st of this year) a request to the Biomedical Advanced Research and Development Authority (BARDA) to fund clinical programs specific to bioterror and pandemic threats. In the meantime, we continue to advance our HCV treatment program at the Medanta Medicity Institute. As previously communicated, positive clinical outcomes from this study will lead to commercialization of our Hemopurifier® in India. Regardless of the many challenges we have confronted, we continue to advance our mission to create innovative devices that address unmet medical needs in cancer, infectious disease and other life-threatening conditions. On behalf of your dedicated team at Aethlon Medical, I again thank you for your continued support and belief in our endeavors.
Very truly yours,
James A. Joyce
Chairman, CEO
Solicitation Number:
HHS-NIH-NCI-SBSS-TSB-110088-04
Notice Type:
Sources Sought
Synopsis:
Added: Jun 30, 2011 12:39 pm
This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice.
This National Cancer Institute (NCI), National Institutes of Health (NIH) project is for the renewal of contract HHSN261201000085I, with CCS Associates, Inc. (CCSA) that was awarded for a one year period. Freedom of Information Act (FOIA) requests regarding the current contract with CCS Associates, Inc. should be directed to Suzy Milliard at milliars@mail.nih.gov. This Small Business Sources Sought Notice (SBSS) is for information and planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the National Cancer Institute (NCI).
A determination by the Government not to compete this requirement as a set-aside based upon responses to this Notice is solely within the discretion of the Government.
Interested parties are expected to review this Notice, the draft Statement of Work to familiarize themselves with the requirements of this project; failure to do so will be at your firm's own risk.
Background:
The National Cancer Institute (NCI) Center for Strategic Scientific Initiatives (CSSI) Office of the Director (CSSI-OD or the Office) has as its mission the task of planning, developing, executing, and implementing rapid strategic scientific and technology initiatives that keep the Institute ahead of the scientific curve with respect to potential new highly productive areas and discoveries. This may involve the development and application of advanced technologies, synergy of large scale and individual initiated research, and/or forging novel partnerships that emphasize innovation, trans-disciplinary teams and convergence of scientific disciplines to enable the translation of discoveries into new interventions, both domestically and in the international arena, to detect, prevent and treat cancer more effectively.
Under the leadership of the NCI CSSI-OD, several efforts are supported both within NCI and outside of NCI to carry-out its function of supporting timely execution and implementation of activities that have trans-NCI benefit. The Office is responsible for coordinating trans-NIH efforts through implementation of interagency and public private collaborations to enable progress against cancer. For example, the NCI-FDA Interagency Oncology Task Force (IOTF) focuses on the identification of scientific and process gaps in the regulatory pathways for cancer interventions and development of joint science-based approaches to addressing these barriers. Also, the Cancer Steering Committee of the Foundation for NIH (FNIH) Biomarkers Consortium is a public private partnership including NCI, FDA, Centers for Medicare and Medicaid Services (CMS), academia, the pharmaceutical and biotechnology industries, and advocates which plans and implements projects to develop and qualify biomarkers for use in accelerating oncology drug development and improving cancer patient management.
Within the Center, CSSI-OD oversees several Offices which together aims to accelerate our understanding of cancer and best practices in research and treatment via cutting edge technologies that take advantage of collaborative efforts to transfer knowledge and insights available from a spectrum of basic and applied research through programs and offices that include: (1) The Cancer Genome Atlas (TCGA) Program Office; (2) Office of Cancer Nanotechnology Research; (3) Office of Cancer Clinical Proteomics Research; (4) Office of Physical Sciences-Oncology; (5) Office of Biorepositories and Biospecimen Research; (6) Office of Cancer Genomics; (7) Knowledge Management and Special Projects Branch; (8) Center for Global Cancer Health Research. These offices support extramural research programs and lead standards and policy development initiatives with the goal of accelerating advances in biomedical technology and furthering the vision of personalized medicine.
The increasing success and development of these strategic scientific initiatives has created a requirement for a wide and changing spectrum of expertise that can be applied to support the efforts of CSSI, including activities in such areas as drug and device development, biomarker development and validation for use in drug development, U.S. regulatory requirements for investigational new drugs and investigational new devices, standard operating procedures for clinical laboratory research, clinical considerations in imaging probe development, clinical trial design in the development of biomarkers and imaging modalities as biomarkers that can be used in drug development, treatment, and monitoring of therapeutic responses.
Effort anticipated under this requirement could include, but not be limited to, continuation of assistance for CSSI-OD and CSSI Offices by providing scientific and project planning support for activities which require expertise in oncology, drug development, advanced technologies applied to drug and device development, biomarker science, and imaging technologies, regulatory affairs, research project management, clinical trial management, business plan development, scientific writing, meeting implementation, and general business documentation.
Purpose and Objectives:
The purpose of this Small Business Sources Sought Notice is to identify qualified small business concerns including HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses, veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses that are interested in and capable of performing the work described herein. The NCI does not intend to award a contract on the basis of responses received nor otherwise pay for the preparation of any information submitted.
As a result of this SBSS Notice, the NCI may issue a Request for Quote (RFQ). THERE IS NO SOLICITATION AVAILABLE AT THIS TIME. However, should such a requirement materialize, no basis for claims against NCI shall arise as a result of a response to this Small Business Sources Sought Notice or the NCI's use of such information as either part of our evaluation process or in developing specifications for any subsequent requirement.
If an RFQ is issued, the NCI anticipates that one (1) award may result from the issuance of the RFQ.
The intent is to procure this requirement as a commercial item purchase order.
Project Requirements:
Independently, and not as an agent of the Government, the Contractor shall perform the services described in the attached Draft Statement of Work (SOW). The Contractor shall provide qualified personnel, material, equipment and facilities not otherwise provided by the Government during the performance of this contract.
Anticipated Period of Performance:
The period of performance for this requirement is five (5) years, consisting of a one-year base period plus four (4) one-year options. The anticipated start date is September 30, 2011.
Draft Statement of Work:
A copy of the draft Statement of Work (SOW), which is subject to revisions, is attached to this sources sought announcement or may be accessed on the NCI Office of Acquisitions Website at URL: http://rcb.nci.nih.gov once there, click on Current Requests for Proposals.
NAICS Code and Size Standard:
In the event an RFQ is issued, North American Industry Classification System (NAICS) code 541690with a size standard of 7.0 million dollars is being considered.
Capability Statement/Information Sought:
Tailored Capability Statements shall demonstrate a clear understanding of all tasks specified in the draft Statement of Work (SOW). Tailored Capability Statements for this requirement shall address the following areas:
Exosomes: a new hope in RNAi delivery
06/02/2011 Vincent Shen
With no feasible delivery mechanism in sight, pharmaceutical companies are pulling the plug on RNAi research programs. Vincent Shen looks at how an exosome delivery system may revive RNAi therapeutics.
Acuity Pharmaceuticals introduced the first RNA interference (RNAi)–based drug candidate, Cand5, into clinical trials in 2004, after having raised $20 million dollars. Cand5 was designed to reduce vision loss in adults with wet age-related macular degeneration (AMD). Other pharmaceutical companies also began introducing RNAi therapeutics into clinical trials and expanding RNAi research programs. The future looked bright for RNAi.
But in 2009, clinical trials of Cand5 were stopped after the guidance committee found the drug was unlikely to significantly prevent vision loss. The small interfering RNA (siRNA) was not being taken up by the targeted cells in the quantities necessary to be effective. Such siRNA delivery problems plagued other RNAi clinical trials as well, leading some pharmaceutical companies to exit RNAi research by 2010.
But S. Patrick Walton, an associate professor of chemical engineering and materials science at Michigan State University, believes it’s too early to bury RNAi therapeutics just yet. “If we look at small molecule drug development, we are still not perfect at it, and we have been doing it for 50-odd years or more,” Walton says. “If we look at RNAi drug development, we have been doing it for 15 years or less. It is still a fairly short horizon from initial discovery to what it would be if it were in the market now.”
The problem underlying delivery of siRNA stems from RNA’s inherent vulnerability; the small RNAs trek through an extracellular jungle filled with ribonucleases. And even if the siRNAs reaches their target tissue intact, it’s still unknown exactly how they penetrate the cell membrane.
To help bring the first RNAi-based therapeutic to patients, some researchers are looking at how cells transfer RNA between one another using the extracellular vesicles called exosomes. Researchers hope these vessels can solve the RNAi delivery problem and open the floodgates for a multitude of RNAi-based drugs that could target diseases such as HIV, hepatitis B, acute renal failure, and AMD.
High-hanging fruit
Acuity Pharmaceuticals was not naive about RNAi delivery problems in 2004. Founded in 2002 by researchers from the Scheie Eye Institute of the University of Pennsylvania (UPenn) Medical School and Samuel Reich, a doctoral candidate in UPenn’s ophthalmology department, the company knew all about extracellular ribonucleases and their destructive effect on siRNA.
So Reich and his cofounders sought to minimize this effect by administering Cand5 through local injection into the patient’s eye. They hoped that reducing the distance the siRNA drug had to travel would improve its deliverability. Once injected, the siRNAs would target retinal cells and knock down vascular endothelial growth factor (VEGF), an extracellular molecule that stimulates the formation of new blood vessels and leads to the overgrowth of these vessels in AMD patients.
The outlook for Cand5 was promising. A preclinical study demonstrated that Cand5’s sequence actively knocked down the expression of VEGF messenger RNA (mRNA) in human cervical and kidney cells. A subsequent study in 2008 found that Cand5—later renamed bevasiranib—could reach its targeted tissue through local injection. The clinical trials found the treatment reduced patient symptoms without significant toxicological effects.
Although Phase I and Phase II trials showed positive results, the company—which was renamed Opko Health—stopped Phase III clinical trials of bevasiranib because it was found to be ineffective. In 2008 University of Kentucky researchers found evidence that the initial positive results might have been from off-target effects and questioned whether the drug actually entered the targeted cells at all (1).
Despite this setback, Opko Health continues its development of bevasiranib, working on “new dosing schedules, combining it with marketed products for AMD, and enhancing delivery with novel siRNA delivery vehicles,” according to the company’s web site. Furthermore, in February 2011, Opko Health paid $10 million to acquire Curna, Inc., a Jupiter, Florida–based company that is developing RNAi drugs to upregulate proteins to treat various diseases.
“RNAi is one of those boom-or-bust kinds of technologies at this point. If somebody finds one that does work and can be delivered accurately to the appropriate tissues and cells, then it has the potential to change the game of therapeutics entirely,” Walton says. “This first-to-market potential is very attractive, even if it’s a high-hanging fruit.” But some pharmaceutical companies have decided that the high-hanging fruit of RNAi therapeutics might not be worth the investment.
Roche, one such company, is terminating its effort to discover and develop drugs through RNAi, affecting research programs in its Kulmbach, Germany, Nutley, NJ, and Madison, WI, facilities. It also ended partnerships with RNAi-biotechnology companies Alnylam Pharmaceuticals, Inc. and Tekmira Pharmaceuticals Corp. Alnylam received $335 million from Roche in 2007 alone; Tekmira received $18.4 million from Roche between 2009 and 2010.
Bursting the RNAi delivery bubble
For pharmaceutical companies like Opko Health that remain vested in RNAi drug development, their efforts continue to focus on improving deliverability. Three RNAi delivery vehicles still hold the spotlight: viruses, cationic liposomes, and cationic polymers. While each can deliver siRNA, each also has the potential to cause more harm than good.
For example, nonpathogenic viral particles packed with DNA sequences can hijack the host’s cellular machinery to produce the siRNAs that knock down a targeted gene, but these transcribed siRNAs—which are produced as short hairpin RNAs—have caused liver toxicity and morbidity in preclinical models. Liposome-based methods unload their siRNA cargo directly into the cell via RNA-bearing endosomes, but these endosomes might trigger an immune response through the activation of toll-like receptors (TLRs), marking the cell for destruction by the immune system. A cationic polymer such as synthetic polyethylamine can deliver siRNA into a cell through an endosome, releasing its payload by rupturing the endosome; however, this could release the lysosomal protease cathespin B, which can then cleave procaspases and trigger apoptosis. So the need for more options has remained constant in RNAi drug development.
In 2007 Hadi Valadi was a postdoctoral researcher in Jan Lötvall’s lab at the Krefting Research Centre, part of the University of Gothenburg; he was working on translational research when he discovered a potentially new form of siRNA delivery via extracellular vesicles called exosomes (2).
Exosomes, first identified in sheep cells in 1983, were believed to be a mechanism for the exchange of proteins between cells. A wide range of cells secrete these small vesicles by endocytosing a portion of their own cell membrane, which they then expel as small vesicles from late endosomes .
But while studying these exosomes in human and mice mast cells, Valadi discovered that proteins weren’t the only molecules hitching a ride in them—mRNAs were tagging along as well. Using microarrays, Valadi and colleagues found mRNA from about 1300 different genes in the exosomes.
When the exosomal mRNAs were introduced into rabbit reticulocyte lysates with radiolabeled methionine, Valadi observed freshly synthesized proteins, indicating that cells could alter the gene expression of neighboring cells by sending out exosomes with functional RNAs. In short, exosomes can deliver functional RNA to another cell without any negative side effects.
“The exosomes have evolved to transfer genetic materials between cells in our bodies,” Valadi says.
Valadi’s discovery sparked interest in this poorly understood function of exosomes. In 2008, researchers from Massachusetts General Hospital discovered that human glioblastomas isolated from tumors in the brain secreted RNA-carrying exosomes. In 2011, Valadi, now an associate professor of rheumatology and inflammation at the University of Gothenburg, found that RNA-filled exosomes exist in human breast milk, saliva, and plasma.
Putting exosomes to work
In 2011, Matthew Wood, an investigator in the Department of Physiology, Anatomy, and Genetics at the University of Oxford, and colleagues decided to put exosomes to the RNAi delivery test.
To start, Wood’s team turned dendritic cells—which present foreign antigens to other immune cells—into factories producing exosomes that target brain cells. To do this, the researchers transfected a DNA sequence that encoded a fusion protein made of rabies virus glycoprotein (RVG)—which targets brain cells—and Lamp2b, a protein expressed on the surface of exosomes. The transfected DNA tricked the dendritic cells into secreting RVG-bearing exosomes that home in on the acetylcholine receptors of the brain’s neurons.
Next the researchers loaded the exosomes with their siRNA cargo. Wood’s group electroporated the exosomes with siRNAs that targeted the metabolic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) found in the majority of cells.
Then these RVG-coated, siRNA-charged exosomes were introduced into a mouse’s circulatory system and peripheral tissues by means of intravenous injection in the tail. This contrasts starkly with Opko Health’s localized injection of RNAi therapeutics close to the targeted tissue. Wood’s team harvested the mouse brain three days post-injection and analyzed the distribution of exosomes in the striatum, cortex, and mid-brain tissues.
Quantitative PCR analysis revealed that the siRNA-containing exosomes knocked down GAPDH mRNA preferentially in all three samples of those brain tissues compared to other tissue samples, including muscle, liver, spleen, and heart. Similarly, Western blotting showed that repression of GAPDH protein synthesis occurred in the cortex. The RVG-coated exosomes had concentrated in the brain and released their gene-silencing payload intracellularly in the target tissue.
“These exosomes can be practically nonimmunogenic for patients. Cells can be isolated from one person and one tissue and modified in vitro,” Valadi says. “We can then give it back to the same person.”
Furthermore Wood and colleagues also designed a disease-treating exosome. This time, they incorporated an siRNA sequence that targeted BACE1, an extracellular protease that triggers the formation of plaque in Alzheimer’s disease. Mice that received an injection of this exosome showed repressed levels of BACE1 protein in the cortex.
In principle, Wood’s exosome method could be applied to a variety of diseases. Swapping the RVG module for another tissue-specific homing peptides could fine-tune the vehicle’s tissue targeting. The exosome’s bilayer shields siRNAs from the extracellular ribonucleases during the nanoparticle’s commute to the target tissue while bypassing any TLR-triggered immune response by entering a cell through membrane fusion, using the dendritic CD9 receptor.
“The exosome field is a very new area, so we need much more time to develop the methodology for using the exosome as a vector,” Valadi says.
Currently researchers are expanding the range of targets to tissues other than the brain. In particular they are searching for surface receptors that exhibit muscle-specificity and mediate entry into skeletal muscle cells. Such a surface tag could lead to treatments for muscular dystrophy, a collection of inheritable human disorders that weaken the skeletal muscles of both children and adults.
“If someone comes up with a technology that is a game changer from the standpoint of delivery, then that will revive some interest,” Walton says.
References
1. Kleinman ME, et al. 2008. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452:591–7.
2. Valadi H, et al. 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 9:654–9.
3. Alvarez-Erviti L, et al. 2011. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 29:341–5.
Innovation
Therapeutic Applications of Exosomes/Microvesicles from Bone Marrow Mesenchymal Cells in Pumonary Diseases
Children's Hospital Boston
posted on 06/11/2011
The inventors have discovered that isolated exosomes/microvesicles from bone-marrow mesenchymal/stromal cells (BMSC) are efficacious in treating and preventing hypoxia-induced pulmonary hypertension in mouse models. This discovery establishes that exosomes are the therapeutic vector of BMSC action. The inventors also devised methods to isolate and characterize exosomes for therapeutic uses. Although these results demonstrate that BMSC exosomes are effective in treating pulmonary diseases, it is highly probable that they may be effective in other diseases, such as those that are in current clinical trials using live BMSC injections.
Exosomes Released by Melanoma Cells Prepare Sentinel Lymph Nodes for Tumor Metastasis
Joshua L. Hood, Roman Susana San, and Samuel A. Wickline
Abstract
Exosomes are naturally occurring biological nanovesicles utilized by tumors to communicate signals to local and remote cells and tissues. Melanoma exosomes can incite a proangiogenic signaling program capable of remodeling tissue matrices. In this study, we show exosome-mediated conditioning of lymph nodes and define microanatomic responses that license metastasis of melanoma cells. Homing of melanoma exosomes to sentinel lymph nodes imposes synchronized molecular signals that effect melanoma cell recruitment, extracellular matrix deposition, and vascular proliferation in the lymph nodes. Our findings highlight the pathophysiologic role and mechanisms of an exosome-mediated process of microanatomic niche preparation that facilitates lymphatic metastasis by cancer cells. Cancer Res; 71(11); 3792–801. ©2011 AACR.
Use of exosome analysis to reveal glioma-specific genetic changes in patient serum
ASCO Annual Meeting — Chicago, IL (June 2011)
Authors: B. Carter1, F. Hochberg2, X. Breakefield2, L. Balaj2, S. Sivaraman2, W. Curry2, S.N. Kalkanis3, L. Loguidice3, L.M. Russo4, M. Noerhelm4, J. Skog2,4
Affiliations: 1University of California, San Diego, La Jolla, CA; 2Massachusetts General Hospital, Boston, MA, USA; 3Henry Ford Health System, Detroit, MI, USA; 4Exosome Diagnostics, New York, NY, USA
Background: Microvesicles (including exosomes) are small lipid bilayer vesicles released from all cells into bodily fluids and have been shown to harbor both RNA and DNA from the parent cell from which they were released. Recently, a rapid method to extract high integrity RNA from serum microvesicles was developed allowing reliable assessment of their mRNA content. This allows us to gain a transcriptional profile of brain tumors without the need for invasive biopsy. Here we use serum microvesicles to examine the expression pattern of various genes in glioblastoma patients including specific mutations such as the EGFRvIII gene.
Conclusions: These data indicated that microvesicle RNA can reveal glioma specific genetic changes in patient serum. This may have utility in detecting brain tumors via a serum assay or analyzing specific genetic changes in a glioblastoma patient without invasive brain biopsy.
Exosomal-miRNA profiles as diagnostic and prognostic biomarkers in head and neck squamous cell carcinoma (HNSCC).
Meeting:
2011 ASCO Annual Meeting
Citation:
J Clin Oncol 29: 2011 (suppl; abstr 5515^)
Author(s):
G. Rabinowits, C. G. Taylor, G. H. Kloecker, A. Patel, M. B. Hall, D. D. Taylor; James Graham Brown Cancer Center, University of Louisville, Louisville, KY
Abstract:
Background: Predicting individual responses of HNSCC to treatment remain challenging. Better methods of defining HNSCC are needed. Improvements in biomarker research will probably be achieved with sets of various genomic and proteomic markers as provided by microarray technology. In previous work we demonstrated that the pattern of plasma exosomal-miRNA mirrored the miRNA within the tissue. Here we report the potential for blood-borne miRNA to identify HNSCC and to predict outcome.
Conclusions: miRNA profiles within blood-borne exosomes may have utility in the HNSCC diagnosis, and appear to be useful as disease monitoring. While these findings need to be confirmed in larger studies, determination of miRNA profiles within plasma-derived exosomes will add a new tool to histology directed therapy.
Role of exosomes released by chronic myelogenous leukemia cells in angiogenesis
Simona Taverna1,†, Anna Flugy1,†, Laura Saieva1,†, Elise C Kohn2, Alessandra Santoro3, Serena Meraviglia1, Giacomo De Leo1, Riccardo Alessandro1,*,‡DOI: 10.1002/ijc.26217
Issue
International Journal of Cancer
Author Information
1Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Sezione di Biologia e Genetica, Università di Palermo, Italy
2Molecular Signaling Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
3Laboratorio di Diagnostica Integrata Oncoematologica,Ospedali Riuniti “Villa Sofia-Cervello”
*Correspondence: Riccardo Alessandro, Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Via Divisi 83, 90133 Palermo
Funded by
Italian Association for Cancer Research
University of Palermo
Intramural Program of the Center for Cancer Research
National Cancer Institute
National Institutes of Health, USA
Abstract
The present study is designed to assess if exosomes released from Chronic Myelogenous Leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of adhesion of CML cells to a HUVEC monolayer. We further showed that the treatment with exosomes from CML cells caused an increase in endothelial cell motility accompanied by a loss of VE-cadherin and ß-catenin from the endothelial cell surface. Functional characterization of exosomes isolated from CML patients confirmed the data obtained with exosomes derived from CML cell line. CML exosomes caused reorganization into tubes of HUVEC cells cultured on Matrigel. When added to Matrigel plugs in vivo, exosomes induced ingrowth of murine endothelial cells and vascularization of the Matrigel plugs. Our results suggest for the first time that exosomes released from CML cells directly affect endothelial cells modulating the process of neovascularization.
Exosomes - Body fluid derived exosomes as a novel template for clinical diagnostics
Sascha Keller2* , Johannes Ridinger2* , Anne-Kathleen Rupp2 , Johannes WG Janssen1 and Peter Altevogt2
1 Department for Human Genetics, University of Heidelberg, D-69120 Heidelberg, Germany
2 Tumor Immunology Programme, D015, German Cancer Research Center, D-69120 Heidelberg, Germany
Journal of Translational Medicine 2011, 9:86doi:10.1186/1479-5876-9-86
Published: 8 June 2011
Abstract
Background
Exosomes are small membrane vesicles with a size of 40-100 nm that are released by different cell types from a late endosomal cellular compartment. They can be found in various body fluids including plasma, malignant ascites, urine, amniotic fluid and saliva. Exosomes contain proteins, miRNAs and mRNAs (exosome shuttle RNA, esRNA) that could serve as novel platform for diagnosis.
Method
We isolated exosomes from amniotic fluid, saliva and urine by differential centrifugation on sucrose gradients. Marker proteins were identified by Western blot and FACS analysis after adsorption of exosomes to latex beads. We extracted esRNA from exosomes, carried out RT-PCR, and analyzed amplified products by restriction length polymorphism.
Results
Exosomes were positive for the marker proteins CD24, CD9, Annexin-1 and Hsp70 and displayed the correct buoyant density and orientation of antigens. In sucrose gradients the exosomal fractions contained esRNA that could be isolated with sufficient quantity for further analysis. EsRNAs were protected in exosomes from enzymatic degradation. Amniotic fluid esRNA served as template for the typing of the CD24 single nucleotide polymorphism (rs52812045). It also allowed sex determination of the fetus based on the detection of the male specific ZFY gene product.
Conclusions
Our data demonstrate that exosomes from body fluids carry esRNAs which can be analyzed and offers access to the transcriptome of the host organism. The exosomal lipid bilayer protects the genetic information from degradation. As the isolation of exosomes is a minimally invasive procedure, this technique opens new possibilities for diagnostics.
Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
Aled Clayton, Saly Al-Taei, Jason Webber, Malcolm D. Mason and Zsuzsanna Tabi
+ Author Affiliations
Department of Pharmacology, Radiology and Oncology, School of Medicine, Cardiff University, Velindre Cancer Centre, Whitchurch, Cardiff CF14 2TL, United Kingdom
Abstract
Extracellular adenosine is elevated in cancer tissue, and it negatively regulates local immune responses. Adenosine production from extracellular ATP has attracted attention as a mechanism of regulatory T cell-mediated immune regulation. In this study, we examined whether small vesicles secreted by cancer cells, called exosomes, contribute to extracellular adenosine production and hence modulate immune effector cells indirectly. We found exosomes from diverse cancer cell types exhibit potent ATP- and 5'AMP-phosphohydrolytic activity, partly attributed to exosomally expressed CD39 and CD73, respectively. Comparable levels of activity were seen with exosomes from pleural effusions of mesothelioma patients. In such fluids, exosomes accounted for 20% of the total ATP-hydrolytic activity. Exosomes can perform both hydrolytic steps sequentially to form adenosine from ATP. This exosome-generated adenosine can trigger a cAMP response in adenosine A2A receptor-positive but not A2A receptor-negative cells. Similarly, significantly elevated cAMP was also triggered in Jurkat cells by adding exosomes with ATP but not by adding exosomes or ATP alone. A proportion of healthy donor T cells constitutively express CD39 and/or CD73. Activation of T cells by CD3/CD28 cross-linking could be inhibited by exogenously added 5'AMP in a CD73-dependent manner. However, 5'AMP converted to adenosine by exosomes inhibits T cell activation independently of T cell CD73 expression. This T cell inhibition was mediated through the adenosine A2A receptor. In summary, the data highlight exosome enzymic activity in the production of extracellular adenosine, and this may play a contributory role in negative modulation of T cells in the tumor environment. Footnotes
This work was supported by grants from Cancer Research Wales and the British Lung Foundation.
The online version of this article contains supplemental material.
Received November 24, 2010.
Accepted May 10, 2011.
GE Global research!
ping_pow_princess
Thank you for the link. The abstracts are very informative. Now the DLT BAA makes more sense. Also it becomes clear who some of the partnering companies/institutions are going to be.
Exosome Biomarkers (THB 3243)
February 4, 2011, 9:18 pm
Exosomes are small vesicles produced by mammalian cells. Exosomes have been studied both as a physiological phenomenon and also as a potential cancer vaccine candidate. The Category A Biothreat bacterium, Francisella tularensis and its related species cause exosome formation in infected mammalian host cells and these exosomes often incorporate Francisella proteins. Thus, exosomes containing such proteins represent a biomarker of infection by F. tularensis and may be developed as a diagnostic tool for the detection of this biothreat agent.
http://www.trans-hit.com/component/k2/itemlist/tag/Infections-Other?tid%5B0%5D=290
more on exosomes -
http://f1000.com/reports/b/3/15/pdf
Aliquots — research highlights from VUMC laboratories
6/30/2011 -
New mode of growth factor signaling
Mutations that increase the expression or activity of the epidermal growth factor receptor (EGFR) are associated with several cancer types. Seven different growth factors, also called ligands, bind to EGFR and have three recognized modes of signaling – autocrine, paracrine and juxtacrine.
Robert Coffey, M.D., and colleagues have identified a new mode of EGFR ligand signaling via exosomes – small (30-90nm) membrane-bound vesicles – and have dubbed this new mode of growth factor signaling extracrine (exosomal targeted receptor activation). They show that human breast and colorectal cancer cells release exosomes containing full-length, signaling-competent EGFR ligands. Exosomes containing the ligand amphiregulin increased invasiveness of breast cancer cells 4-fold over exosomes containing two other EGFR ligands (TGF-a and HB-EGF).
The findings, published in Current Biology, suggest that this new mode of EGFR ligand signaling could have important implications for cancer invasion, metastasis and the tendency of cancer cells to cause changes to normal cells that surround them (cancer field effect).
— Melissa Marino
MiRNA profiling of tumor-derived exosomes
by Vitrant, David-Georges, Ph.D., UNIVERSITY OF PITTSBURGH, 2010, 110 pages; 3435558
Abstract:
Cancers and infectious diseases are becoming a growing public health problem in the world today. The importance of my work for public health is in detecting these diseases earlier and more accurately, potentially leading to better therapies and higher survival rates for patients. Current diagnostic techniques focus on detecting antibodies from serum, gene expression and miRNA profiles of tumor tissues and, more recently, in the bodily fluids of patients.
This dissertation shows a novel technique that makes use of small microvesicles called exosomes and the microRNAs (miRNAs) they carry for the potential diagnosis of cancer. Exosomes are small (40-100 nm) membrane-bound vesicles that are created from the inverse budding of the multivesicular endosome and originate from a variety of tumor types. Exosomes can be easily purified from cell cultures and serum of patients and have recently been shown to carry small non-coding RNAs called miRNAs. In the first part of this study, I developed techniques that enabled us to increase the amount of our exosome and total RNA starting material before proceeding to use these as potential diagnostics for head and neck cancers.
Although the use of exosomes to diagnose diseases is not novel, the use of miRNAs present in tumor-derived exosomes is a new approach. In the final two chapters, I discuss the use of exosomes to diagnose KSHV viral infections as well as head and neck cancer. Increasing the accuracy and reducing the amount of starting material needed for these studies would provide a non-invasive technique to detect viral infections and cancers. This would help in providing earlier therapeutic treatments and help to increase the longevity and quality of life of patients.
Exosomes from Human Saliva as a Source of MicroRNA Biomarkers
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Sunday, January 03, 2010
Oral Diseases
A Michael, SD Bajracharya, PST Yuen, H Zhou, RA Star, GG Illei, I Alevizos
Volume 16 Issue 1, Pages 34 - 38
Objective: The aim of this study was to examine the presence of microRNAs (miRNAs) within exosomes isolated from human saliva and to optimize and test methods for successful downstream applications.
Design: Exosomes isolated from fresh and frozen glandular and whole human saliva were used as a source of miRNAs. The presence of miRNAs was validated with TaqMan quantitative PCR and miRNA microarrays.
Results: We successfully isolated exosomes from human saliva from healthy controls and a patient with Sjögren's syndrome. microRNAs extracted from the exosomal fraction were sufficient for quantitative PCR and microarray profiling.
Conclusions: The isolation of miRNAs from easily and non-invasively obtained salivary exosomes with subsequent characterization of the miRNA expression patterns is promising for the development of future biomarkers of the diagnosis and prognosis of various salivary gland pathologies
Exosomes as biomarker treasure chests for prostate cancer - Abstract
Wed, 09 February 2011
Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Although progress has been made with regard to types of markers (protein, DNA, RNA, and metabolites) and implementation of improved technologies (mass spectrometry, arrays, and deep sequencing), the discovery of novel biomarkers for prostate cancer (PCa) in complex fluids, such as serum and urine, remains a challenge. Meanwhile, recent studies have reported that many cancer-derived proteins and RNAs are secreted through small vesicles known as exosomes.
This narrative review describes recent progress in exosome research, focusing on the potential role of exosomes as novel biomarkers for PCa. The purpose of this review is to acquaint clinicians and researchers in the field of urology with the potential role of exosomes as biomarker treasure chests and with their clinical value.
Medline and Embase entries between 1966 and September 2010 were searched using the keywords exosomes, microvesicles, prostasomes, biomarkers, prostate cancer, and urology. Leading publications and articles constructively contributing to exosome research were selected for this review.
Exosomes are small vesicles (50-100nm) secreted by almost all tissues; they represent their tissue origin. Purification of prostate- and PCa-derived exosomes will allow us to profile exosomes, providing a promising source of protein and RNA biomarkers for PCa. This profiling will contribute to the discovery of novel markers for the early diagnosis and reliable prognosis of PCa.
Although the initial results are promising, further investigations are required to assess the clinical value of these exosomes in PCa.
Written by:
Duijvesz D, Luider T, Bangma CH, Jenster G. Are you the author?
Reference: Eur Urol. 2010 Dec 29. Epub ahead of print.
doi: 10.1016/j.eururo.2010.12.031
PubMed Abstract
PMID: 21196075
UroToday.com Prostate Cancer Section
Landmark Publication Reports Potential of Exosomes as Biomarkers for Early Disease Detection Using NanoSight's NTA Technology
(Nanowerk News)
The rapidly growing field of exosomes and microvesicles is highlighted in a new paper in NanoMedicine. Titled "Sizing and phenotyping of cellulars vesicles using Nanoparticle Tracking Analysis", it has been authored by a team led by Professors Ian Sargent and Paul Harrison.
Professor Ian Sargent from the Nuffield Department of Obstetrics & Gynaecology, Oxford University
Cellular microvesicles and exosomes (nanovesicles) are involved in many disease processes and have been shown to have major potential for use as biomarkers. However, developments in this area have been constrained by limitations in the technology available for their measurement. This ground-breaking paper reports on the use of fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles. In the NTA system, manufactured by NanoSight (Amesbury, UK), vesicles are visualized by light scattering using a light microscope. A video is recorded and then the NTA software tracks the Brownian motion of the individual vesicles calculating their size and total concentration. Using human placental vesicles and plasma, the team has demonstrated that NTA can measure cellular vesicles as small as ~50 nm which is far more sensitive than conventional flow cytometry (lower limit ~300 nm). By combining NTA with fluorescence measurement, it has been sho wn that vesicles can be labeled with specific antibody-conjugated quantum dots, allowing their phenotype to be determined.
Comprehensive funding for the work was provided by a Wellcome Trust Technology Development, a Wellcome Trust Programme Grant and by the Oxford Partnership Comprehensive Biomedical Research Centre with support from the Department of Health's NIHR Biomedical Research Centres funding scheme.
To learn about the characterization of exosomes and microvesicles using NanoSight's unique nanoparticle tracking analysis solutions, please visit the company website (www.nanosight.com) and register for the latest issue of NanoTrail, the company's electronic newsletter.
About NanoSight
NanoSight delivers the world's most versatile and proven multi-parameter nanoparticle analysis in a single instrument.
NanoSight's "Nanoparticle Tracking Analysis" (NTA) detects and visualizes populations of nanoparticles in liquids down to 10nm, dependent on material, and measures the size of each particle from direct observations of diffusion. Particle size, concentration, Zeta potential and aggregation can all be analyzed while a fluorescence mode provides differentiation of labelled particles. This particle-by-particle methodology goes beyond traditional light scattering and other ensemble techniques in providing high-resolution particle size distributions.
NanoSight's comprehensive characterization matches the demands of complex biological systems, hence its wide application in development of drug delivery systems, of viral vaccines, in nanotoxicology and in biodiagnostics. This real-time data gives insight into the kinetics of protein aggregation and other time-dependent phenomena in a qualitative and quantitative manner.
NanoSight has a growing role in biodiagnostics, being proven in detection and speciation of nanovesicles (exosomes) and microvesicles. As functionalized nanoparticles increasingly fulfill their potential in biodiagnostics, NanoSight is ever more the analytical platform of choice.
NanoSight demonstrates worldwide success through rapid adoption of NTA, having installed more than 300 systems worldwide with users including BASF, GlaxoSmithKline, Merck, Novartis, Pfizer, Proctor and Gamble, Roche and Unilever together with the most eminent universities and research institutes. In addition to this user base more than 250 third party papers citing NanoSight results consolidate NanoSight's leadership position in nanoparticle characterization. For more information, visit the NanoSight website (www.nanosight.com).
DIALYSIS LIKE THERAPEUTICS (DLT)
Overwhelming infection of the bloodstream, or sepsis, is a significant cause of injury and death among combat-injured soldiers and civilians. The goal of the Dialysis Like Therapeutics (DLT) program is to develop a portable device that removes "dirty" blood from the body, separates harmful agents, and returns "clean" blood to the body in a manner similar to dialysis treatment of kidney failure. The device could dramatically decrease the morbidity and mortality of sepsis, thereby saving thousands of lives and billions of dollars in the United States each year.
To do so, the DLT program seeks to develop multiple component technologies, integrate them into a portable device, and rigorously validate device effectiveness. Key technical areas and representative technical approaches include:
Persistent interrogation of the entire blood volume via sensing technologies such as miniaturized immunofluorescent assays and surface enhanced Raman spectroscopy (SERS). This capability can enable early identification of bacteria, viruses, toxins, and cytokines.
High-flow fluid manipulation without the use of anticoagulants via novel biocompatible/biomimetic architectures and advanced surface functionalization chemistries.
Continuous removal of pathogens, toxins, activated cells, exosomes, and cytokines via a diverse suite of "label-free" technologies such as synthetic mannose binding lectins, custom aptamers, selective adsorption, acoustophoresis, dielectrophoresis, and inertial separation.
Closed-loop therapy with system feedback to monitor and redirect patient state based on conditional probability and reduced order techniques.
The integration and validation of these component technologies will focus on developing an innovative path to FDA investigational device exemption (IDE) before the completion of the program. From there, the device would be available for transition to military medical commands and clinical trials required for final regulatory approval.
Hopefully the HP will be a part of the "combination therapy" in the future
HIV Prevention Needs Combo Approach
By Michael Smith,
Published: July 02, 2011
Combinations of drugs have slowed the progress of HIV infection in individual patients.
Now combinations of prevention approaches are needed to slow the progress of the HIV pandemic, according to a policy forum published in the July 1 issue of Science.
Testing such combinations is "the next imperative" for HIV prevention research, according to Robin Shattock, PhD, of Imperial College London, and colleagues.
Clinical trials that aim to determine safety and efficacy of individual interventions should remain a priority but, they wrote, "we recommend a broadening of focus to accelerate rigorous evaluation of combination approaches."
Success in randomized clinical trials would offer "hope, at last, for a tangible impact on halting and reversing the HIV pandemic," Shattock and colleagues argued.
The Science article comes a few weeks before the Rome conference of the International AIDS Society, where Shattock is scheduled to deliver a plenary address urging increased research into ways of combining prevention tools.
Although highly active antiretroviral therapy (HAART) is beneficial for individuals (and there is growing evidence that it can play a preventive role), the pandemic continues to outpace available medication resources, the researchers noted.
Currently, 6.6 million people with HIV are on HAART, but 9 million are on waiting lists and two people are newly infected for every person starting therapy, they noted.
Without reducing the incidence of the disease, Shattock and colleagues argued, "issues of sustainability" seem inevitable.
But over the past several years, a number of population-based prevention approaches have been shown to work, more or less, including:
Male circumcision, which reduces the risk of heterosexual men acquiring HIV
Daily oral tenofovir plus emtricitabine (Truvada) used as pre-exposure prophylaxis by HIV-negative men who have sex with men
A 1% tenofovir microbicide gel applied vaginally before and after sex by HIV-negative heterosexual women
A prime-boost HIV vaccine
Immediate HAART -- before a medical indication -- for the HIV-positive partners in discordant heterosexual couples to prevent sexual transmission of the virus
Combining some of those might yield a bigger bang for the prevention buck, Shattock and colleagues argued.
For instance, immediate HAART in discordant heterosexual couples would be a problem in some areas, where only about half of the people who need drugs for medical reasons can get them.
But combining that approach with pre-exposure prophylaxis for the uninfected partner might create a more cost-effective option, the researchers argued
A combination of circumcision and pre-exposure prophylaxis might have synergistic benefits as well, they argued.
But a highly effective vaccine would have the greatest impact on the pandemic, they argued, noting that the vaccine tested in the so-called RV144 trial had a significant but small benefit.
But it's "plausible" that people taking pre-exposure prophylaxis might have a more robust response to the vaccine, they said, and such a hypothesis should be tested along with others.
Primary source: Science
Source reference:
Shattock RJ, et al "Turning the Tide Against HIV" Science 2011; 333: 4
DIGESTIVE DISEASES AND SCIENCES
DOI: 10.1007/s10620-011-1802-z
Direct Medical Care Costs Among Pegylated Interferon Plus Ribavirin-Treated and Untreated Chronic Hepatitis C Patients
M. Solomon, M. Bonafede, K. Pan, K. Wilson, C. Beam, P. Chakravarti and B. Spiegel
Abstract
Background
Hepatitis C virus (HCV) is a common and expensive infectious disease. The current standard of care for HCV infection, pegylated interferon with ribavirin (PEG–RBV), is costly and has a significant adverse event profile.
Aim
To quantify the direct economic burden of HCV infection and PEG–RBV treatment for HCV.
Methods
Using a large administrative claims database, we evaluated the medical and prescription drug costs of patients with HCV from 2002 to 2007. A cohort of patients with PEG–RBV was 1:1 propensity score-matched to a cohort of untreated HCV patients. Multivariate models adjusted for demographic and clinical characteristics in evaluating the effect of PEG–RBV treatment on direct medical expenditure.
Results
The matched analysis included 20,002 patients. PEG–RBV-treated patients had higher total direct medical costs (28547vs 21,752; P < 0.001), outpatient pharmacy costs (17419vs 2,900; P < 0.001), and outpatient physician visit costs (894vs787; P < 0.001), but lower inpatient costs (3942vs 9,543; P < 0.001) and emergency room costs (366vs505; P < 0.001). After multivariate adjustment, PEG–RBV use was associated with an additional 9423intotaldirectmedicalcostsandanadditional 12,244 in HCV-related total medical costs.
Conclusion
Total HCV-related medical costs are higher for treated than untreated patients, driven mostly by higher outpatient pharmacy costs, which outweigh higher HCV-related inpatient costs incurred by untreated patients.
Repost -
The Gray Sheet
June 6, 2011 Volume 37 Number 23 Page 22
Aethlon Aims To Lure Drug Makers To Device Biz
With Disease-Filtering Technology
Aethlon Medical is looking to repurpose the disease-filtering technology behind its investigational
Hemopurifier device to attract drug company partnerships.
The company's pitch to pharmaceutical firms: Instead of taking on the substantial regulatory and
commercialization burdens of developing a systemically delivered medicine, reach market much
quicker and at a lower cost by attaching your drug candidates to a dialysis-type device designed to
filter disease agents from the blood.
Compared to drug development, the device route "can be a very efficient pathway,” Aethlon
Chairman and CEO Jim Joyce said in an interview.
While the revenue potential of taking the device route may not be as high as in the pharmaceutical
space, Aethlon says its proposed model could be ideal for certain situations, particularly if a drug
developer is running into safety issues with the systemic delivery of a promising therapy.
Also, the strategy may be viewed as a stepping stone to the larger drug market, the San Diego-based
firm suggests. By partnering with Aethlon on device development, a drug company could start
earning revenue earlier, "perhaps allowing them to access the resources to meet longer-term
objectives of having that same compound move forward in the market as a systemically injected
compound," Joyce explained.
The CEO says his firm is in early discussions with several drug companies about prospects to partner
on product development with the newly introduced Aethlon ADAPT filtration platform technology,
but it is too soon to name names.
“We seek collaborative relationships that provide us with near-term development revenues in
addition to potential long-term royalty streams from commercialized products,” Joyce said.
"The timing for introducing our platform could not be better considering the scope of increasing and
unpredictable regulatory challenges faced by therapeutic drug developers."
Genesis Is Hemopurifier Viral Filtration Device
The genesis of the ADAPT platform is Aethlon's development-stage Hemopurifier viral filtration
system, which employs an “affinity treatment cartridge” that rapidly separates and captures
infectious viruses and toxins from a patient’s blood as it circulates outside of the body.
.
The single-use cartridge is designed to work in
conjunction with portable pumps or dialysis
machines already in the hospital or clinic. Blood
circulation is established into the system via a
catheter or other blood access device, and the
entire circulatory system can pass through the
device in as little as 15 minutes, the company
says.
Internally, Aethlon is developing it as therapy for
"category A" bioterrorism threats and the
hepatitis C virus, among other infectious diseases.
It is also hoping to win a government contract to
develop its system to treat sepsis.
But the device maker is trying to sell drug
developers on the prospect of swapping out inhouse
Aethlon affinity agents with compounds
owned by the pharmaceutical firm, which could
either be clinical-stage drugs, already marketed products or agents that have previously failed clinical
drug studies.
Aethlon sees potential for the system in treating a large variety of high-risk diseases, and would ink
agreements in clinical areas that won't compete with what the company is developing internally.
Selling Point: Avoid Toxicity, Adverse Interactions
A principal selling point to drug firms, according to Joyce, is the prospect of bypassing serious safety
issues for candidates with promising efficacy profiles.
For instance, he pointed to a theoretical case of a cancer drug candidate that has demonstrated
safety on its own but exhibits troubling interactions with other drugs likely to be part of a
chemotherapy regimen.
“The combined toxicity becomes problematic for advancing the compound,” Joyce noted.
But if you attach the drug candidate to the filtration system instead of delivering it systemically, it
inherently eliminates the risks of drug toxicity and drug-drug interactions, Aethlon points out.
It also can provide a way around certain contraindications of medications. For instance, the antivascular
endothelial growth factor cancer drug Avastin can't be used in patients from about one
month prior through about one month following surgery due to bleeding risks, among other issues.
"An extracorporeal device that could selectively be clearing VEGF, or perhaps other growth factors,
out of the circulatory system might prove to be very beneficial, especially during that [pre- and postsurgical]
window," Joyce said.
Aethlon also points to the potential to employ larger quantities of an affinity agent than could safely
be delivered into the body, and to prevent resistance to certain types of drug therapies that build up
over time, such as in the case of HIV therapies. (See “ Expanding HIV Therapy: Will Devices Pick Up
Where Drugs Leave Off? ” – “The Gray Sheet” Sept. 4, 2006.)
In addition, the company says its technology can be used to target a variety of drug agents within a
single device "to address multiple factors underlying a single disease condition.”
Part 2 - Slides (most of them) from the recent RedChip conference -
http://aethlonmedical.investorroom.com/index.php?s=19
The Hemopurifier®
A Broad-Spectrum Therapeutic Device
• Hepatitis C
• HIV
• Cancer
• Bioterror & Pandemic Threats
Investment Highlight
The Hemopurifier® Addresses
Unmet Medical Needs
Bioterror & Pandemic Threats
Unmet Medical Need Targeted by the Aethlon Hemopurifier®
• Fulfills the HHS broad-spectrum
treatment mandate
• Solution for emerging or released
pathogens not addressed by
drugs or vaccines
• Solution for genetically modified
or synthetically engineered
pathogens
Human Immunodeficiency Virus (HIV)
Unmet Medical Need Targeted by the Aethlon Hemopurifier®
• A solution to drug resistance
• Removes all viral strains
• Captures immunosuppressive
gp120
• Research study has been
initiated to test the capture of
HIV-released exosomes that
transport NEF protein
Hepatitis C Virus (HCV)
Unmet Medical Need Targeted by the Aethlon Hemopurifier®
• Addresses all genotypes
• Accelerates viral load depletion
w/o drug toxicity and interaction
risks
• Selective mechanism advances
proven benefit of therapeutic
filtration without removing
essential blood components
Cancer
Unmet Medical Need Targeted by the Aethlon Hemopurifier®
• The first therapeutic strategy to
address exosomes released by
cancer
• Induce apoptosis
• Disrupt T-cell signaling
• Inhibit anti-cancer cytokine
production
• Angiogenesis
• Metastasis
In Vitro Confirmations Against
Bioterror and Pandemic Threats
Virus Collaborator
Ebola USAMRIID/CDC
Dengue NIV/WHO
Lassa SFBR
West Nile Battelle
H5N1 Avian Battelle
1918-r Spanish Flu Battelle
2009 H1N1 Swine Battelle
Monkey Pox Battelle
HIV-AIDS Study
• Infected dialysis patient
• 12 treatments / 30 days
• 4 hrs per treatment
• Performed in absence of drug
therapy
• Average per treatment viral load
reduction of 54%
• Improved CD4 t-cell ratios
Human HCV Studies
• Average per treatment viral load
reduction of 64%
• Infected dialysis patients
• 4 hour treatments
• Performed in absence of drug
therapy
• Calculated from 36 treatments
In vitro Cancer
Exosome Validations
• Ovarian
• Breast
• Colorectal
• Lymphoma
• Melanoma
Hemopurifier® therapy can be delivered through the
established global infrastructure of dialysis machines
(90,000 in U.S. alone
The Early Adopter Distribution Channel
• 20,000 Nephrologists who will know how to administer Hemopurifier®
therapy
• Over 15,000 dialysis centers available to become official Hemopurifier®
therapy locations
• No additional infrastructure required
• 2 million dialysis patients already being treated by Nephrologists
• Incidence of HCV is 100-1000x greater than general population
• Dialysis patients also have higher incidences of Cancer and HIV
• Hemopurifier® therapy can be administered during scheduled dialysis treatments
4 Paths to Early Revenue
1. Aethlon ADAPT™ system revenues
2. Government Contract or Grant Income
3. Research Diagnostics
4. Hemopurifier® Commercialization
4 Paths to Early Revenue
1.) Aethlon ADAPT™ System Revenues
• Multi-channel revenue opportunity driven by future
products created through drug industry
collaborations
• Product development fees
• Fees from research, regulatory, and manufacturing
support
• Downstream royalties
4 Paths to Early Revenue
2.) Government Contract or Grant Income
• Pending Contract Award –DARPA-BAA-11-30
entitled, "Dialysis-Like Therapeutics”
• Pending – Response to BARDA CBRN
BAA-11-100-00009 submitted on May 31, 2011
• Forthcoming submission – U.S. Army, Blood
Purification for Organ Failure SBIR due June 29th
4 Paths to Early Revenue
3.) Research Diagnostics
• Licensing or initial sales of our ELLSA research
diagnostic tools that identify and quantify exosomes
• Over 70% of researchers polled in market survey
indicated interest in purchasing the product
4 Paths to Early Revenue
4.) Hemopurifier® Commercialization
• A 30 patient study underway at the Medanta-Medicity Institute in Delhi,
India
• Treatment target: HCV
• Primary study objective: To demonstrate Hemopurifier® therapy
accelerates early viral load depletion when combined with HCVSOC
therapy
• Achievement of study objectives will trigger first commercialization
in India
• Program now established to fund HCV drug cost for enrolled patients.
Acceleration of enrollment now expected.
Part 1 - Slides from the recent Red Chip conference - I have cut/pasted them directly from JJ's talk - mainly for new investors
http://aethlonmedical.investorroom.com/index.php?s=19
Investment Highlights
• Adaptable Therapeutic Filtration Device Platform
• Our Products Address Unmet Medical Needs
• Our Products Address Large Markets
• Early Adopter Distribution Channel in Place
• 4 Paths To Early Revenue
• New Clinical Programs
The Aethlon ADAPT™ System
Adaptive Dialysis-like Affinity Platform Technology
• Converges proven plasma membrane technology with antibodies or other
affinity drug agents
• Provides foundation for an expansive pipeline of selective therapeutic
filtration (STF) devices
• Transforms drug agent mechanism from biologic to less burdensome
medical device regulatory pathway
• Repurposes development-stage, clinical-stage, branded, and clinical
dropout affinity drugs
The Adapt™ System Pipeline
Introduced to the drug industry on May 25th, 2011
• The Aethlon Hemopurifier®
• STF device to address trauma related organ failure
• To be proposed in the coming week in response to a U.S. Army funding program
• STF device to reduce incidence of sepsis
• Proposed to the Defense Advanced Research Projects Agency (DARPA)
• DARPA-BAA-11-30 “Dialysis-Like Therapeutics” contract response on April 1, 2011
• $14.2 million requested
DIALYSIS LIKE THERAPEUTICS (DLT) PROGRAM DESCRIPTION ON DARPA WEBSITE
Overwhelming infection of the bloodstream, or sepsis, is a significant cause of injury and death among
combat-injured soldiers and civilians. The goal of the Dialysis Like Therapeutics (DLT) program is to
develop a portable device that removes "dirty" blood from the body, separates harmful agents, and
returns "clean" blood to the body in a manner similar to dialysis treatment of kidney failure. The device
could dramatically decrease the morbidity and mortality of sepsis, thereby saving thousands of lives
and billions of dollars in the United States each year.
To do so, the DLT program seeks to develop multiple component technologies, integrate them into a
portable device, and rigorously validate device effectiveness. Key technical areas and representative
technical approaches include:
Persistent interrogation of the entire blood volume via sensing technologies such as miniaturized
immunofluorescent assays and surface enhanced Raman spectroscopy (SERS). This capability can
enable early identification of bacteria, viruses, toxins, and cytokines.
High-flow fluid manipulation without the use of anticoagulants via novel biocompatible/
biomimetic architectures and advanced surface functionalization chemistries.
Continuous removal of pathogens, toxins, activated cells, exosomes, and cytokines via a
diverse suite of "label-free" technologies such as synthetic mannose binding lectins, custom
aptamers, selective adsorption, acoustophoresis, dielectrophoresis, and inertial separation.
Closed-loop therapy with system feedback to monitor and redirect patient state based on conditional
probability and reduced order techniques.
The integration and validation of these component technologies will focus on developing an innovative
path to FDA investigational device exemption (IDE) before the completion of the program. From there,
the device would be available for transition to military medical commands and clinical trials required for
final regulatory approval.
DARPA-BAA-11-30 “Dialysis-Like Therapeutics”
• Our proposal was selected for funding
• No assurance that we receive a contract award
• We are adapting our statement of work to meet budget allocation
• Then we move into contracting process
• No assurance that Aethlon and DARPA mutually agree to terms
Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National Institute on Aging (NIA/NIH), (http://www.nia.nih.gov/)
National Institute on Alcohol Abuse and Alcoholism (NIAAA/NIH), (http://www.niaaa.nih.gov/)
National Institute of Allergy and Infectious Diseases (NIAID/NIH), (http://www3.niaid.nih.gov/)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS/NIH), (http://www.niams.nih.gov/)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH), (http://www.niddk.nih.gov/)
National Institute on Drug Abuse (NIDA/NIH), (http://www.nida.nih.gov/)
National Institute of General Medical Sciences (NIGMS/NIH), (http://www.nigms.nih.gov/)
National Heart, Lung, and Blood Institute (NHLBI/NIH), (http://www.nhlbi.nih.gov/index.htm)
National Center for Complementary and Alternative Medicine (NCCAM/NIH), (http://nccam.nih.gov/)
National Center for Research Resources (NCRR/NIH), (http://www.ncrr.nih.gov/)
Title: SHIFT Award: Small Businesses Helping Investigators to Fuel the Translation of Scientific Discoveries [SBIR: R43/R44]
Announcement Type:
New
Update: The following update relating to this announcement has been issued:
February 8, 2011 - See Notice NOT-AI-11-030 The purpose of this Notice is to highlight NIAID’s interest in receiving grant applications to develop strategies, methods and/or tools to optimize influenza vaccine production.
August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.
September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011. Adobe B1 forms are required for due dates on or after May 8, 2011.
Program Announcement (PA) Number: PA-10-122
NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.
This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).
IMPORTANT: A registration process in Grants.gov and eRA Commons is necessary before submission. Applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.
A compatible version of Adobe Reader is required for download. For Assistance downloading this or any Grants.gov application package, please contact Grants.gov Customer Support at http://grants.gov/CustomerSupport.
Catalog of Federal Domestic Assistance Number(s)
93.213, 93.273, 93.279, 93.389, 93.837, 93.838, 93.839,93.846, 93.847, 93.855, 93.856, 93.859, 93.865, 93.866
Key Dates
Release/Posted Date: March 5, 2010
Opening Date: March 5, 2010 (Earliest date an application may be submitted to Grants.gov)
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: January 8, 2013
Due Dates for E.O. 12372
Not Applicable
Additional Overview Content
Executive Summary
Purpose. The primary objectives of the SHIFT SBIR initiative are: (1) to foster research that is translational in nature and (2) to transform academic scientific discoveries into commercial products and services. Academic researchers can be a driving force for new products and services in a small business concern (SBC). A major feature of the SHIFT program includes the requirement for an investigator who is primarily employed by a United States research institution at the time of application to transition to a small business concern (SBC) and be primarily employed (more than 50% time) by the SBC by or at the time of award. A SHIFT SBIR grant enables an SBC to increase both its scientific research staff and its core competencies. The Project Director/Principal Investigator (PD/PI) may also facilitate SBC licensing of intellectual property (IP) from the PD/PI’s prior academic institutions, promote collaboration opportunities with academic investigators, and enable better access to academic resources.
Mechanism of Support. This FOA will utilize the SBIR (R43/R44) grant mechanisms for Phase I, Phase II, and Fast-Track applications.
Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. The total amount awarded and the number of awards will depend upon the quality, duration, and costs of the applications received.
Budget and Project Period. Well-justified budgets up to $200,000 total costs per year and time periods up to 2 years may be requested for Phase I. Well-justified budgets up to $750,000 total costs per year and time periods up to 3 years may be requested for Phase II. Phase II Competing Renewal applications must be submitted in accordance with participating Institute’s or Center’s specific budget limitations described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA.
Eligible Institutions/Organizations. Only United States SBCs may submit SBIR applications and receive SBIR awards. An SBC is one that, on the date of award for both Phase I and Phase II funding agreements, meets ALL of the criteria as described in Section III.
Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. On an SBIR application, the PD/PI must have his/her primary employment (more than 50%) with the SBC at the time of award and for the duration of the project. For this FOA, the PD/PI transitioning from the academic institution must be primarily employed by his/her research institution at the time of application and must be primarily employed (more than 50% time) by the SBC by or at the time of award. Primary employment with a small business concern precludes full-time employment at another organization. See Section III.1.B for additional requirements.
Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.
Number of Applications. Applicant SBCs may submit more than one application, provided each application is scientifically distinct.
Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).
Renewals. Only SBIR Phase II awardees are eligible to submit a SBIR Phase II Competing Renewal application, which should represent a continuation of support for research and development of the previous work funded by the original SBIR Phase II grant. SBIR Phase II Competing Renewal applications will be accepted by only those Institutes or Centers described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA.
Application Materials. See Section IV.1 for application materials.
General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:
SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
Hearing Impaired. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.
Table of Contents
--------------------------------------------------------------------------------
Part I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
3. Anticipated Announcement and Award Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
Part II - Full Text of Announcement
--------------------------------------------------------------------------------
Section I. Funding Opportunity Description
--------------------------------------------------------------------------------
1. Research Objectives
The primary objectives of the SHIFT SBIR initiative are to foster research that is translational in nature and to transform academic scientific discoveries into commercial products and services. A major feature of the SHIFT program includes the opportunity for SBCs to hire skilled academic investigators (e.g., senior postdoctoral fellow, research associate, engineer or faculty) to be a Project Director/Principal Investigator (PD/PI) on an SBIR grant. The PD/PI must bring extensive research knowledge, skills and demonstrated abilities (e.g., publications, patents, and copyrights) to the SBC.
Academic researchers can be a driving force for new products and services in a small business concern (SBC). A SHIFT SBIR grant may enable an SBC to increase both its scientific research staff and its core competencies. The PD/PI may also facilitate SBC licensing of intellectual property (IP) from the PD/PI’s prior academic institutions, promote collaboration opportunities with academic investigators, and enable better access to academic resources. The SBC is responsible for assuring that the SBC is able to meet the research goals submitted in its application, including addressing appropriate access to any technology and/or IP from relevant IP owners (e.g., IP from the PD/PI’s previous institution).Note that the authorizing legislation for the SBIR program (Small Business Innovation Development Act of 1982) provides for retention by an SBC of the rights to data generated by the SBC in the performance of an SBIR award.
Examples of potential projects include, but are not limited to the topics listed below.
Note: These topics are not intended to represent an exhaustive list. The potential projects for research and development (R&D) are as extensive as the missions of the ICs participating in the SHIFT FOA. Therefore, applicants are encouraged to contact program staff listed in Section VIII to discuss their R&D ideas.
Applying opportunities in genomics and other high throughput technologies to understand fundamental biology, and to uncover the causes of specific diseases
Translating basic science discoveries into new and better treatments
Development of diagnostics, preventative strategies and therapeutic tools
Development and clinical evaluation of biomarkers for alcohol exposure and alcohol-induced tissue injury
Therapeutic development for alcoholism treatment
Diagnostic assessment and treatment of alcohol use disorders and comorbidity
Alcohol biosensors and data analysis systems
Prevention, diagnosis, and treatment of fetal alcohol spectrum disorder and alcohol-related birth defects
Minimal dose post-exposure vaccine for rabies
Immunotherapy to kill HIV-infected cells
Asthma therapeutic vaccine
Novel antifibrotic therapies for progressive liver failure
Diagnostic measurement devices or methods for assessment of urinary leakage and incontinence
Therapeutics for diabetic wound healing
Pediatric formulations
Robust diagnostic biosensors for infants
mHealth tools for assessing and addressing health in children and families
Wearable diagnostic and therapeutic devices for physiologic monitoring and interventions
Wearable biosensors for persons with genetic sensitivity to environmental factors
Therapeutic interventions for persons with physical and developmental disabilities
Advancement of novel botanical therapies for effective symptom management of non-life-threatening conditions
Development of interactive technologies to improve and expand delivery of mind/body interventions
Discovery of improved methodology for the characterization of plants and their secondary metabolites
Development of standardized, objective methods to assess patient adherence to specific CAM treatment interventions;
Development of devices/tools to assess consistency and fidelity of practitioner approaches and other aspects of protocol implementation
Virtual settings or online tools for clinician training and implementation of fidelity monitors
Development and validation of enhanced patient-reported outcome assessment tools for CAM (e.g. new user (clinician, researcher, and/or patient/study volunteer)–friendly interfaces, methods to improve compatibility with research and health informatics systems currently in use)
Development of measurement tools for assessing expectancy for effects of CAM mind-body medicine, acupuncture, and manual therapy interventions
Novel technologies that enhance/track/monitor “real time” adherence to drug abuse (and HIV+) treatment regimens
Technology to improve the efficacy of substance abuse treatment, treatment adherence, and reduce recidivism among criminally-involved patients
Mobile and/or internet technology based treatment interventions to augment traditional substance use disorder (SUD) treatments and their outcome
Technologies and/or devices to boost medication adherence for SUD patients
Technology-based treatment platforms to standardize interventions and to make them more community-friendly
Integrate item response theory and computer adaptive testing in measures of addiction liability.
Brief screening tools to assess relapse risks in and out drug treatment settings
Use of the internet to link community based outreach and HIV testing services to facilitate access by drug users and their sex partners in neighborhood settings.
Development of novel therapeutics, diagnostics, and devices for treating heart, lung, blood and sleep diseases and disorders
New or improved measures, analytical methods, and instruments for gene expression in individuals with heart, lung, blood, and sleep disorders and diseases
Health-care systems and outcomes research, including development of new quality measures for evidence-based heart, lung, blood, and sleep health care
Models of behavior modification and other approaches to behavior change related to heart, lung, blood, and sleep diseases and disorders
Devices and technologies to prevent cardiac ischemia/reperfusion injury
Vaccines for the prevention or treatment of heart, lung, and blood diseases
Non-invasive methods to diagnose DVT and PE
Technologies and strategies to advance cellular therapies for heart, lung and non-malignant blood diseases
Therapies to treat hematologic diseases and cytopenic states
Technologies for in vitro reduction, inactivation or removal of microorganisms and other infectious moieties from blood, blood components, and plasma derivatives
Development of products, technologies and services to diagnose, treat and/or prevent skin and rheumatic diseases, muscle disorders, and joint and bone diseases
See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.
Section II. Award Information
--------------------------------------------------------------------------------
1. Mechanism(s) of Support
This funding opportunity will use the Small Business Innovation Research (SBIR [R43/R44] grant mechanisms. Applications may be submitted for support as Phase I, Phase II, or Fast-Track grants as described in the SF424 (R&R) SBIR/STTR Application Guide.
Small business concerns that have received a Phase I SBIR grant may apply for Phase II funding of that project. The Phase II must be a logical extension of the Phase I research but not necessarily as a Phase I project supported in response to this funding opportunity. SBIR Phase II applications will compete with all SBIR applications and will be reviewed according to the customary peer review procedures. Applications for SBIR Phase II Competing Renewal grants will be accepted by only those ICs described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA.
The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.
This funding opportunity uses “Just-in-Time” information concepts. The modular budget format is not accepted for SBIR grant applications. Applicants must complete and submit budget requests using the SF424 Research and Related (R&R) Budget component found in the application package attached to this FOA in Grants.gov/Apply.
2. Funds Available
Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. The total amount awarded and the number of awards will depend upon the quality, duration, and costs of the applications received.
The SF424 (R&R) SBIR/STTR Application Guide indicates the statutory guidelines of funding support and project duration periods for Phase I and Phase II SBIR awards. Phase I awards normally may not exceed $100,000 total for a period normally not to exceed 6 months. Phase II awards normally may not exceed $750,000 total for a period normally not to exceed 2 years. These award levels and project periods are statutory guidelines, not ceilings. Therefore, applicants are encouraged to propose a budget and project duration period that are reasonable and appropriate for completion of the research project.
For this FOA, well justified budgets up to $200,000 total costs per year and time periods up to 2 years for Phase I may be requested. Budgets up to $750,000 total costs per year for up to 3 years may be requested for Phase II. Total costs include direct costs, Facilities & Administrative (F&A)/indirect costs, and fee.
SBIR Phase II Competing Renewal budgets must be submitted in accordance with participating IC-specific budget limitations described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Part I Overview Information
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Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov)
Title: NIAID Clinical Trial Planning Grant (R34)
Announcement Type
This is Funding Opportunity Announcement (FOA) a reissue with modifications of PAR-06-384
Update: The following update relating to this announcement has been issued:
August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.
September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011. Adobe B1 forms are required for due dates on or after May 8, 2011.
May 5, 2010 - See Notice NOT-AI-10-024 New NIAID Policy: Investigator-Initiated Clinical Trials.
Program Announcement (PA) Number: PAR-10-185
NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.
This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).
A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.
A compatible version of Adobe Reader is required for download. For Assistance downloading this or any Grants.gov application package, please contact Grants.gov Customer Support at http://grants.gov/CustomerSupport.
Catalog of Federal Domestic Assistance Number(s)
93.855, 93.856
Key Dates
Release/Posted Date: May 5, 2010
Opening Date: June 22, 2010 (Earliest date an application may be submitted to Grants.gov)
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s) for AIDS & Non-AIDS: July 22, 2010, September 13, 2010, January 13, 2011, May 13, 2011, September 13, 2011, January 13, 2012, May 14, 2012, September 13, 2012, January 14, 2013
Peer Review Date(s): September, 2010, December, 2010, April, 2011, August, 2011, December, 2011, April, 2012, August, 2012, December 2012, April, 2013
Council Review Date(s):, January 2011, May, 2011, October, 2011, January 2012, May, 2012, October, 2012, January 2013, May 2013
Earliest Anticipated Start Date(s): November, 2010, March, 2011, July, 2011, November, 2011, March 2012, July, 2012, November 2012, March, 2013, July 2013
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: January 15, 2013
Due Dates for E.O. 12372
Not Applicable.
Additional Overview Content
Executive Summary
Purpose. This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications that propose the complete planning, design, and preparation of documentation necessary for implementation of investigator-initiated clinical trials. The trials must be hypothesis-driven, milestone-defined, related to the research mission of the NIAID and considered high priority by the Institute. Investigators are encouraged to visit the NIAID website for additional information about the research mission and high-priority research areas of the NIAID http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/.)
Mechanism of Support. This FOA will utilize the NIH clinical trial planning (R34) grant mechanism and runs in parallel with two related FOAs, PAR-10-184 and PAR-10-186, that invite applications that propose implementation of non-high-risk and high-risk investigator-initiated clinical trials, respectively. Pre-approval by the NIAID is required for submission of an application under all three FOAs.
Funds Available and Anticipated Number of Awards. The total amount awarded and the number of awards will depend upon the numbers, quality, duration, and costs of the applications received.
Budget and Project Period. Budgets for direct costs of up to $150,000 and a project duration of up to one year may be requested.
Application Research Strategy Length: The R34 application Research Strategy section may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts. See http://grants1.nih.gov/grants/funding/funding_program.htm
Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.
Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.
Resubmissions. Applicants may submit a resubmission application, but such applications must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016). Resubmission applications from PAR-06-384 (http://grants.nih.gov/grants/guide/pa-files/PAR-06-384.html) are allowed. All resubmission applications require pre-approval by the NIAID.
Renewals. Renewal applications are not allowed under this FOA.
Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
Application Materials. See Section IV.1 for application materials.
General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:
SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936
Table of Contents
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Part I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria
Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
3. Anticipated Announcement and Award Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting
Section VII. Agency Contacts
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
Part II - Full Text of Announcement
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Section I. Funding Opportunity Description
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1. Research Objectives
This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications that propose planning, design, and preparation of documentation necessary for implementation of investigator-initiated clinical trials. A clinical trial is defined by NIH as:
“a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective”.
The NIAID Clinical Trial Planning Grant will support planning for clinical trials that address high-priority research questions related to the mission and goals of the NIAID. Sufficient pre-clinical data to support the planning of the clinical trial should be available prior to submission of the R34 grant application. The trials must be hypothesis-driven and milestone-defined
The NIAID Clinical Trial Planning (R34) Grant is not a prerequisite for submission of the R01 or U01 application for implementation of investigator-initiated clinical trials.
Background
In FY2009 NIAID funded $1.36 billion in clinical research. A subset of this funding was devoted to clinical trials, which is one research strategy NIAID uses to improve the understanding of the clinical mechanisms of infectious, immunologic, and allergic diseases and to improve prevention, diagnosis, and treatment. For additional information about the mission, strategic plan, and research interests of the NIAID, applicants are encouraged to consult the NIAID web site http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/.
Clinical Trial Infrastructure
Historically, NIAID has supported a wide variety of clinical research activities through a clinical trial infrastructure funded through cooperative agreements, solicited under NIAID Requests for Applications (RFAs), and contracts, solicited under NIAID Requests for Proposals (RFPs). This infrastructure focuses on high-priority disease research areas. Examples include the HIV/AIDS Clinical Trial Networks supported by the Division of AIDS (http://www3.niaid.nih.gov/about/organization/daids/Networks/daidsnetworks.htm), the Division of Microbiology and Infectious Diseases Clinical Trials Programs and Networks (http://www3.niaid.nih.gov/about/organization/dmid/programs.htm), and the Immune Tolerance Network supported by the Division of Allergy, Immunology and Transplantation (http://www.immunetolerance.org/). NIAID’s clinical research infrastructure includes coordinating centers, statistical units, data centers, central laboratories, clinical centers, and other specialized resources.
Investigator-Initiated Clinical Trials
Although the clinical research infrastructure is crucial in furthering the Institute’s research, NIAID recognizes that additional models of clinical trial research may be important in furthering its goals for the next decade. Within this framework, the Institute has established the investigator-initiated clinical trial program for clinical trials that cannot or will not be conducted through existing NIAID-supported clinical trial infrastructure. This program consists of support for the NIAID Clinical Trial Planning (R34) Grant, the NIAID Clinical Trial Implementation (R01) Grant and the NIAID Clinical Trial Implementation (U01) Cooperative Agreement. The NIAID Clinical Trial Implementation (R01) Grant (PAR-10-184) is designed to support non-high-risk clinical trials, while the NIAID Clinical Trial Implementation (U01) Cooperative Agreement (PAR-10-186) is designed to support high-risk clinical trials, as defined by NIAID below and in the associated policy statement (see NOT-AI-10-024).
The NIAID Clinical Trial Planning Grant (R34) is available to support planning activities associated with either high- or non-high-risk clinical trials. However, the NIAID Clinical Trial Planning (R34) Grant is not a prerequisite for either NIAID implementation award. The planning grant is designed to: (1) permit early peer review of the rationale for the proposed clinical trial; (2) permit assessment of the design/protocol of the proposed trial in a preliminary form; (3) provide support for the development of a complete study protocol and associated documents, including a manual of operations and (4) support the development of other essential elements of a clinical trial. If a clinical trial is ready for implementation, and readiness is adequately supported by documentation, submission of an R01 or U01 application may occur if prior approval has been provided by NIAID. Note that funding of the Clinical Trial Planning Grant does not guarantee or imply pre-approval to submit an application for or funding of a subsequent NIAID Clinical Trial Implementation (R01) Grant or NIAID Clinical Trial Implementation (U01) Cooperative Agreement.
For additional information about NIAID’s investigator-initiated clinical trial program, see http://funding.niaid.nih.gov/ncn/clinical/iict.htm.
Although the NIAID Clinical Terms of Award will not be applied to planning grant awards, applicants are encouraged to review the NIAID Clinical Terms of Award and associated guidance documents while preparing applications for submission under this FOA (see http://www.niaid.nih.gov/ncn/clinical/clinterm.htm).
Scope
The NIAID Clinical Trial Planning (R34) Grant will support timely development of all materials required for implementation of the future clinical trial.
Awards made under this FOA will support all clinical trial planning activities, including, but not limited to:
establishment of the research team
identification of collaborators and enrollment sites
design of the study
development of the complete clinical protocol
development of the statistical analysis plan
development of the data management plan
development of the informed consent(s) and assent, if applicable, form(s)
development of the investigator’s brochure or equivalent
development of a manual of operations
development of a data sharing plan
development of milestones
development of a plan for the acquisition and administration of study agent(s)
obtaining required Office of Human Research Protections (OHRP) assurances, if not already in place
determination of whether the trial will be conducted under an IND/IDE and who will hold the IND/IDE (NIAID reserves the right to decide whether the applicant should apply for an IND/IDE, as well as the right to hold the IND/IDE.)
development of a complete set of suitable documents for submission to the appropriate regulatory authorities
development of a data and safety monitoring plan
development of a detailed budget for conduct and completion of the clinical trial including funding for preparation of a final study report
development of training materials and training plans for study staff
The R34 planning grant will not support planning for more than one clinical trial or collection of preliminary (clinical or pre-clinical) or prospective data to support the rationale for a clinical trial.
See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.
Section II. Award Information
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1. Mechanism of Support
This FOA will use the NIH Clinical Trial Planning Grant (R34) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.
This FOA uses “Just-in-Time” information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) should use the PHS398 Modular Budget component.
All foreign applicants must complete and submit budget requests using the Research & Related Budget component.
2. Funds Available
Applicants may request support for up to one year with a maximum of $150,000 direct costs.
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NIAID provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.
Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s) National Institutes of Health (NIH)
Components of Participating Organizations National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH))
Funding Opportunity Title Beyond HAART: Innovative Therapies to Control HIV-1 (P01)
Activity Code P01 Research Program Projects
Announcement Type New
Related Notices None
Funding Opportunity Announcement (FOA) Number RFA-AI-11-012
Companion FOA None
Number of Applications See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.855; 93.856; 93.242
FOA Purpose The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH), NIH encourage applications from institutions/organizations to participate in this Funding Opportunity Announcement (FOA), Beyond HAART: Innovative Therapies to Control HIV-1. This initiative will support program project applications to develop therapeutic approaches that could allow HIV-1 infected persons to discontinue current HIV-1 treatments for a sustained period without viral rebound. Approaches of interest include therapeutic vaccines, gene therapies, cell therapies, antibodies, and other targeted interventions. Awardees will perform basic research on the chosen approach, as well as engage in translational activities such as test-of-concept studies in animal models or humans. Research program project applications must be designed as collaborative efforts between academia and the private sector.
Key Dates
Posted Date April 20, 2011
Letter of Intent Due Date June 20, 2011
Application Due Date(s) July 19, 2011
AIDS Application Due Date(s) Not Applicable
Scientific Merit Review November, 2011
Advisory Council Review January, 2012
Earliest Start Date(s) April, 2012
Expiration Date July 20, 2011
Due Dates for E.O. 12372 Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Note: A new version of the paper PHS 398 application form and instructions (revised 6/2009) must now be used. Download the new application form and instructions from http://grants.nih.gov/grants/forms.htm.
Table of Contents
Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Research Objectives
Purpose
This Funding Opportunity Announcement will support program project applications to develop therapeutic approaches that could allow HIV-1 infected persons to discontinue current HIV-1 treatments for a sustained period without viral rebound. Approaches of interest include therapeutic vaccines, gene therapies, cell therapies, antibodies, and other targeted interventions. Applicants are expected to have an identified strategy that is based on a solid scientific rationale and supported by preliminary data. Awardees will perform basic research on the chosen approach, as well as engage in translational activities such as test-of-concept studies in animals or humans. Research program project applications must be designed as collaborative efforts between academia and the private sector.
Background
Combination antiretroviral drug therapy (ART) is very effective at suppressing HIV-1 replication. ART reduces viral load from millions of copies of HIV-1 RNA per ml of plasma to single copy levels, where it can be maintained indefinitely.However, numerous studies have demonstrated that long- term ART, in any number of potent combinations, does not result in a cure. In most infected persons, virus rebound occurs within weeks once drug treatment is interrupted. In order to make progress towards a cure, different or complementary approaches are needed that take into account the existence of latent HIV-1 and occult viral reservoirs in drug-treated individuals.
Finding a cure for HIV-1 infection is one of the highest, long-term priorities of the NIAID. As a consequence, the NIAID is issuing a series of initiatives to stimulate research into the problem of HIV-1 persistence and how it relates to the development of strategies to effect long-term control of HIV-1 in the absence of ART (functional cure) or complete eradication of persistent virus (cure). PA-09-152 (http://grants.nih.gov/grants/guide/pa-files/PA-09-152.html), issued in 2009, focuses on characterizing viral reservoirs in treated persons and on developing tools and assays that could facilitate future clinical interventions. RFA-AI-10-009 (http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-10-009.html), issued in 2010, solicits a collaborative effort to design and test cure strategies. The current FOA addresses the intermediate goal of developing strategies that will control HIV-1 in the absence of ART, through immunological means or by the use of novel technologies. A functional cure would be expected to delay or eliminate rebound of virus when ART is interrupted, reduce exposure to drugs and consequent toxicities, free infected persons from the complexities of continuous drug taking, decrease the potential to transmit virus, and perhaps lower levels of immune activation and resulting long-term morbidities.
Objectives and Scope
Many basic questions remain regarding why and how HIV-1 persists in the face of potent antiretroviral drug treatment. Translational research efforts may provide insights. The objective of this FOA is to encourage investigators to begin considering the kinds of strategies that might effectively convert HIV-1 infected persons on highly active antiretroviral drug regimens into elite controllers, a term used to describe a subset of HIV-1 infected individuals who can suppress viral load (to single copy levels) in the absence of antiretroviral drugs. The mechanism or, more likely, mechanisms responsible for the elite controller phenotype is unknown but current research points to the importance of host genetic factors and immune responses. For this reason, the current FOA encourages research on immunological approaches to control HIV-1. Novel technologies/concepts that might be brought to bear on this problem are also of interest. New ideas about how to control viral replication at a molecular level and how to reduce latent reservoirs will be of value in the search for a functional cure.
Responsive applications to the FOA will propose (and justify) a concept for achieving a functional cure and provide a plan to advance the concept toward testing in an animal model or in humans. This will be achieved through multidisciplinary research, including basic research and translational activities, and will involve both academic and private sector collaborators.
Approaches of interest include, but are not limited to, those listed below:
Therapeutic vaccines, with the exception of dendritic cell-based vaccines.
Cell and gene therapies.
Antibody-based interventions.
RNA-based approaches.
Inhibitors of cellular pathways that interfere with the immune response to HIV-1 or that contribute to immune activation.
Targeting of agents to latent reservoirs or sites of persistent virus replication, including the Central Nervous System.
This FOA will support test-of-concept studies in animals and humans. Such studies must be directly linked to basic research and/or preclinical development performed under the award, and must be initiated prior to the final year of the award. Clinical studies in humans are anticipated to be few in number and of small size (less than 50 subjects), and are subject to prior review by the Scientific Advisory Panel and the NIAID/DAIDS Clinical Sciences Review Committee (CSRC) (for more detailed information, see Section VI.2. Administrative and National Policy Requirements). Larger scale clinical studies will not be supported under this FOA.
The following types of research are not included within the scope of this FOA, since they are either well represented within the NIAID research portfolio or more appropriate for support under other programs or funding mechanisms. Applications proposing research in the areas listed below will be deemed non-responsive to this FOA and will not be reviewed:
Strategies to purge reservoirs by activating T cells (e.g. cytokine cocktails, agonistic antibodies, HDAC inhibitors, and similar approaches), as a monotherapy.
Strategies that rely on frequent (e.g., daily) therapeutic dosing.
Studies on the mechanisms of virus control in persons who can suppress HIV-1 to undetectable levels without antiretroviral drugs.
Dendritic cell-based therapeutic vaccines.
Small molecule drug discovery and development targeting viral replication.
Clinical trials that are ready for implementation without further basic or preclinical research. Such projects can be pursued under another NIAID mechanism, i.e. clinical planning and implementation grants (see http://funding.niaid.nih.gov/researchfunding/qa/pages/iict.aspx).
Research programs focused exclusively on neuroAIDS.
Applicants are strongly encouraged to discuss the proposal approach, concept, or strategy with Program staff listed in Section VII. Agency Contacts to determine if the approach, concept, or strategy meets the stated responsive criteria.
Partnerships
A key component of this initiative is the formation of partnerships between academia and the private sector. For the purpose of this FOA, the term “private sector” comprises large and small, domestic and foreign, not-for-profit and for-profit organizations such as pharmaceutical, biotechnology, bioengineering, and chemical companies.
Each application must be composed of a minimum of two interrelated individual research projects and an Administrative Core. The Project Leader of at least one individual research project of the P01 must be employed by, and represent, a private sector entity, and another Project Leader must be employed by a university or other academic institution. The applicant institution may be either a private sector entity or an academic institution. Applications not meeting the above described composition will be considered non-responsive and will not be reviewed.
The private sector partner should propose a research plan that contributes materially and intellectually to the overall goals and objectives of the P01, contribute expertise and/or resources not generally available in academia, and have a record of past successes moving concepts to practical applications.
For the purpose of this FOA, the following list of activities, alone or in combination, will not be considered sufficient to meet the requirement for private sector participation:
providing access to intellectual property, chemical libraries, or novel experimental therapeutics or providing fee-for-service type activities such as routine in vitro assays, cell processing and preparation, standard pharmacology and toxicology tests.
Intellectual Property
In light of the collaborative nature of this initiative, applicants are encouraged to reach consensus with any proposed partners regarding intellectual property, data sharing, and other legal matters that may arise during the period of the program project in order to ensure that the goals of the overall program project will be met. In addition, applicants are expected to exercise their Bayh-Dole rights in a manner that is consistent with meeting the goals of the award and the intent of the Bayh-Dole Act to promote the utilization, commercialization and availability of U.S. Government-funded inventions for public benefit. Finally, applicants are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID or other mechanisms. See NIH Data Sharing Policy and Implementation Guidance and related NIH sharing policies (at http://sharing.nih.gov) for guidance related to appropriate sharing of research data and resources, consistent with NIH policies, laws, and regulations.
Additional Information Related to the Program Project Application
Research Projects: Required (minimum of two). The P01 program project application must propose at least two individual research projects for the application to be considered responsive. As stated above, one project must originate from an academic institution and one, from the private sector (see Partnerships section). The P01 may be composed of research projects and scientific cores from the same or multiple institutions/organizations as long as the basic requirement for one individual research project from academia and one individual research project from the private sector is met.
Administrative Core: Required. Each application must include an administrative core headed by the contact PD/PI. This core is a resource to the program project grant, providing for the management, coordination and supervision of the overall program project. The Administrative Core section of the application should provide an administrative plan that discusses the structure and roles of administrative staff, including the training and experience of proposed staff and the functions to be performed; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated; and how research related travel and training will be budgeted. Funding for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, and communication expenses should be requested here. Expenses related to the participation of external experts serving on the Scientific Advisory Panel should be included in the Administrative Core budget.
Scientific Core(s): Optional. A scientific core is a resource to the program project grant as a whole and must support at least two of the proposed individual research projects. The application must indicate the specific individual research projects to be served by the Scientific Core(s). This section of the application should present a clear picture of the facilities, techniques, and skills that the core will provide and describe the role of the Scientific Core Leader and each of the key participants. The apportionment of dollars or percentage of dollars that will be required to support each component research project that will utilize each scientific core should also be presented.
Annual meeting: An annual face-to-face meeting is required for each P01. The purpose of the meeting is to review progress, plan and design research activities, and establish priorities. Participants should include at a minimum the PD/PI(s), Leaders of each individual research project and core, the NIAID Program Official, an NIMH program representative, as appropriate, and members of the Scientific Advisory Panel (see below). Applicants should include expenses related to participation in the annual meeting in the budget of the respective individual research project or core applications. See Section VI.2. Administrative and National Policy Requirements.
Scientific Advisory Panel: Following award, the PD/PI(s) of each P01 award (in consultation with the NIAID Program Official) will invite 3 or more experts working in relevant research areas to form a Scientific Advisory Panel (SAP) for the P01. These individuals will be unaffiliated with the application and will provide an independent perspective on the research activities of the P01. The members of the SAP will not be involved in the day to day activities of the P01 but are expected to attend one Annual meeting per year throughout the award period. They will assist in the review of program activities and evaluate progress toward the proposed goals, adherence to the original time frames, and the continued relevance of each project and scientific core to the overall goals of the research program. The SAP may recommend new directions as appropriate. The SAP will provide the PD/PI(s) and the NIAID Program Official with a comprehensive written evaluation of the program’s activities, including the Panel’s recommendations, after each annual meeting. For awards involving clinical trials, the SAP may be asked by the NIAID Program Official to help determine whether sufficient scientific data has been generated by the Program to warrant proceeding to clinical trial. See Section VI.2. Administrative and National Policy Requirements.
Members of the SAP may not be named in the application nor should individuals be invited to be a member in advance of the award. Applications that name potential members of the SAP will not be reviewed.
Section II. Award Information
Funding Instrument Grant
Application Types Allowed New
The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards The following NIH components intend to commit the following amounts in FY 2012:
National Institute of Allergy and Infectious Diseases (NIAID)/Division of AIDS, $4.5 million, 2-3 awards.
National Institute of Mental Health (NIMH)/Division of AIDS Research, $0.5 million, for support of research relevant to the priorities of the NIMH AIDS program. .
Award Budget Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period The scope of the proposed program project application should determine the award period. The maximum project period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
The Future of the NIAID Clinical Trial Units
By Payton Manizhe, Director, Office of Clinical Oversight, Division of AIDS, National Institute of Allergy and Infectious Diseases
As the National Institute of Allergy and Infectious Diseases (NIAID) moves forward to restructure its HIV/AIDS Clinical Trials Networks and include a new network focused on infectious diseases other than AIDS, the Clinical Trial Units (CTUs) will continue to play a critical role in establishing, developing, and implementing the networks’ scientific research agendas. Additionally, we are seeking to strengthen the CTUs to enhance our ability to conduct clinical trials around the world.
CTUs provide the scientific and administrative expertise and infrastructure to implement the scientific agendas of the clinical research networks. Each CTU includes an administrative component with performance and resource management responsibilities and Clinical Research Sites (CRSs), the hospitals, outpatient clinics, health maintenance organizations, community health centers, private physician practices, and clinics where clinical trials are conducted. They provide uniquely identified and characterized potential cohorts (e.g., demographics, incidence and prevalence of HIV/AIDS) as well as qualified professionals with the facilities and resources necessary to conduct clinical research in accordance with Good Clinical Practices. Each CRS will be affiliated with one CTU and support the scientific agenda of one or more networks.
Although these enhanced CTUs will be similar to the existing structures, we anticipate supporting fewer CTUs that will generally be larger in size and scope compared to what we have today. Each CTU will need to affiliate with at least two HIV/AIDS Clinical Trials Networks and have the capacity and flexibility to work with other research networks. CTUs will also have the option of working with the new non-AIDS Infectious Diseases Clinical Trials Network, which will be focused on antimicrobial resistance and emerging infectious diseases.
CTU applicants interested in participating in the non-AIDS network will need to describe, in their applications, their capabilities, including potential investigators, participation in similar research efforts, and infrastructure. Because the exact research agenda for this network is not completely defined, CTU applicants will not need to identify specific performance sites and CRSs in their application. This statement of capability will be judged as either acceptable or unacceptable, rather than given a numerical score as in previous years.
The overall strength of the CTU will be judged in part by the strength of its CRSs, as well as its plan to efficiently coordinate and manage the sites’ activities. Further, we expect CTUs to take on greater responsibility for overall CRS evaluation and performance, in collaboration with the leadership groups for each of the networks for which each site is affiliated. To support greater flexibility to address evolving scientific agendas, CTU principal investigators and site leadership will play a major role in identifying and evaluating sites, including the performance and productivity of CRS pharmacy and laboratory components. For example, an investigator at the CTU level may propose an additional network affiliation to an existing CRS or add new protocol-specific sites to the CTU to meet specific network and/or NIAID research goals. To avoid redundancy and optimize efficiency, the CTUs, in collaboration with network leadership, will have more responsibility for evaluating the ability of specific sites to conduct study protocols, provide operational support to the sites, and drive quality management processes.
Successful collaboration between the network leadership groups and the CTUs will also require transparency in financial and operational matters. For example, the CTUs will have increased responsibility for efficient resource utilization, including reallocation of resources as necessary. The CTUs will also have a substantial coordinating role in administration and resource management (financial, human, technical and clinical) for their individual units and the sites.
Partnerships will also continue to be an essential component of the NIAID clinical trials enterprise. To that end, NIAID remains committed to preserving and strengthening relationships with the communities where we conduct research through community advisory boards. To encourage new scientific research collaborations, NIAID will build a mechanism for allowing other partners (e.g., other NIH Institutes and U.S. Government agencies) to access the CTU infrastructure.
Enabling others to tap into our expansive clinical trial network will build efficiencies into the clinical trials process by helping to meet enrollment targets faster. Similarly, granting access to network resources, such as data management, regulatory and statistical expertise, and clinical monitoring capabilities will also help achieve mutual clinical research goals.
Overall, we believe that these changes will enable the CTUs to provide greater breadth in scientific expertise and capability, increased capacity, and greater flexibility in addressing scientific agendas of the newly awarded clinical trials networks. We welcome your thoughts and feedback.
Incidence of hepatitis C virus infection in patients with chronic kidney disease on conservative therapy
International Journal of Infectious Diseases, 06/20/2011
Li Cavoli G et al. – Hepatitis C virus (HCV) infection is a never–ending public health problem. Many studies have investigated the incidence of HCV infection among dialysis patients, but there have only been a few epidemiological studies in renal conservative therapy. The authors studied 320 subjects with pre–dialysis chronic kidney disease living in Sicily, Italy. The incidence of HCV infection was 6.25%. In Europe, incidence ranges from 0.2% to 3.5%. It appears that the incidence of HCV infection is higher in the studied patient population than in the population as a whole.
Patients with HCV and HIV both - just like pts on dialysis this subgroup may also benefit tremendously from the HP
Rate and Timing of Hepatitis C Virus Relapse after a Successful Course of Pegylated Interferon plus Ribavirin in HIV-Infected and HIV-Uninfected Patients Full Text
Clinical Infectious Diseases
Medrano J et al. – Among 604 patients treated for chronic hepatitis C, the 386 who were human immunodeficiency virus (HIV) positive attained an end-of-treatment response less frequently and experienced relapse more often than did the 218 who were HIV negative. However, episodes of HCV relapse occurred before week 12 in most cases, regardless of HIV status.