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Sad is right. Doubled down yesterday and woke up to a nightmare PR. Was lucky to cut loses at 50% at open and rolled my leftovers into another bio.. now starting to clawback.
Hope it works out for those who chose to hang tough.
So, Execs keep their options to be exercised post RS and common shareholders get diluted? Why list 300/400/500 for 1 if that is not what's being considered. Bad day for longs.
Back on the sidelines for now. Will wait until the RS is effected and buy afterwards ... if pps reverses to uptrend.
Hope this a just one helluva shake for those still holding and you reap the benefit$. GL
A potential punch to the gut on Biogen's MS drug.
Biogen Inc. shares declined in the extended session Wednesday after the U.S. Patent and Trademark Office said Mylan NV could likely succeed in a patent challenge to a Biogen multiple sclerosis drug. Biogen shares fell 2.8% after hours, following a 1.1% decline to close at $333.24. In a decision, the USPTO said that of 20 patent claims against Biogen's drug Tecfidera, Mylan "has demonstrated a reasonable likelihood that it will succeed on at least one of its challenges to patentability."
Last RTQ 315.00
BIIB gaps down $10 at open...
You're Welcome. The cream will rise to the top, no matter how much flak flies. I'm convinced the current team can get the job done. I do feel for the investors that sold and took a big hit. GL
Interesting Read
Which Biopharma Stocks Are Looking To Score Big In Cannabis Medicine?
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ALLISON GATLIN
1/05/2019
Lost in the fray of countless efforts to bring recreational marijuana to a storefront near you, the advent of cannabis medicine by biotech stocks and pharma companies hit several key milestones in 2018, with little fanfare.
The Food and Drug Administration took a historic leap in June when it approved Epidiolex. Made by GW Pharmaceuticals (GWPH), Epidiolex is the first medicine derived from the cannabis plant. The FDA's nod allows it to treat two seizure disorders.
Then in September, the Drug Enforcement Administration made a major policy shift. The DEA listed Epidiolex under Schedule 5 of the Controlled Substances Act, thus declaring that it has a lower potential for abuse than recreational marijuana. Ultimately, Epidiolex hit the market in November.
These steps were the first to approve the controversial substance from a federal government that for decades was reluctant to accept the concept of legal marijuana. Experts believe the door will open further.
Companies ranging from small biotech stocks to giant pharma companies like AbbVie (ABBV) are exploring cannabis medicine and what products can be derived from it. Many companies are in the startup phase. But hundreds of studies are underway on possible uses for cannabis, including many dealing in pain management. And billions of dollars in potential revenue await the biotech stocks and pharma companies that can navigate the tightrope between growing demand and wary regulators.
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"There's too much revenue to be made by states and the federal government (to not allow) cannabis-related drugs and products to become available," said Miracle Mile Advisors portfolio manager Brian Sterz. Miracle Mile is an independent advisory firm in L.A. that works with high-net-worth clients.
Cannabis Uses Still Unidentified
Still, the medicinal cannabis market is in its infancy. Industry and academic experts have yet to identify all the potential uses for the plant — or the molecules that come from it. Some say the market could be in the billions of dollars just in treating pain.
The advent of cannabis medicine and legal marijuana sales are joined at the hip, Sterz says. As more states legalize marijuana — and reap the fruits of sales taxes — cannabis medicine will grab broader appeal.
"We're all taking steps to remove the stigma," he told Investor's Business Daily.
Other biopharma companies and academics are looking to break into this new realm. The U.S. National Library of Medicine's ClinicalTrials.org lists more than 350 studies in cannabis medicine. These are studies of cannabinoids, molecules that come from the cannabis plant.
Laboratory-Created Cannabis
But few have yet to dive into this market with GW Pharma. Other biotech stocks working in cannabis medicine are studying laboratory-created cannabinoids. They include Cara Therapeutics (CARA), Corbus Pharmaceuticals (CRBP), Insys Therapeutics (INSY) and Zynerba Pharmaceuticals (ZYNE).
AbbVie is the only Big Pharma stalwart in the mix, with a drug that treats certain types of nausea and anorexia. A top-rated stock in IBD's Medical-Ethical Drugs industry group, AbbVie has a best-possible Composite Rating of 99. This means AbbVie stock trades in the top 1% of all stocks in terms of key growth metrics. The remaining biopharma stocks active in cannabis medicine all rank in the bottom half of stocks.
Right now, GW Pharma is easily the biggest biotech stock working exclusively in cannabis medicine. The company believes the FDA's approval of Epidiolex in June was an inflection point for cannabis medicine — and others agree.
Cannabis medicine differs from medical marijuana. Medical marijuana is not subject to stringent clinical studies per the FDA. As a result, it can't be reimbursed through insurance.
"We've always believed that we were blazing a trail for the development of cannabinoid medicines in various therapeutic areas," Stephen Schultz, GW's vice president of investor relations, told IBD. "I think the work we're doing clearly points the way on how to do this."
GW Pharma has yet to offer details from the Epidiolex launch. Schultz said "there is significant demand and expectation for access to this product." Epidiolex costs about $32,500 for the first year. That number varies based on the patient's age or weight and the dose of cannabis medicine.
Tough To Size Up The Market
So sizing the market is a challenge, Schultz says. The National Organization for Rare Diseases estimates two in 100,000 children born each year will have Lennox-Gastaut syndrome, one of two disorders that Epidiolex can treat. The population of Dravet syndrome patients — the other disorder — is even smaller.
"Beyond the regulatory approved medicines, it's almost impossible to try to size the market," he said.
Unlike its brethren, GW Pharma uses the cannabis plant in its drug development. The biotech stock also plans to soon seek FDA approval of another cannabis medicine called Sativex in spasticity tied to multiple sclerosis.
There are certain hurdles to using the cannabis plant or creating the molecules that come from it, says Zynerba Chief Executive Armando Anido. To do so, biotech stocks like Zynerba must have the proper DEA licenses. But that's not abnormal, he says. Many experimental drugs are subject to DEA scrutiny.
"If you want to go down the pathway of getting a drug approved by the Food and Drug Administration, and we currently have a Schedule 1 requirement on our CBD (cannabidiol), you have to work with the DEA in order to do that," he told IBD. "To me, that's something that's part of how we develop drugs."
Hard Time Accessing Cannabis
The DEA considers Schedule 1 drugs, like the CBD used by Zynerba, as having a higher potential for abuse and no proven medical benefit. Thus, biotech stocks can have a hard time accessing the plant itself for testing. Zynerba, for example, uses laboratory-created cannabinoids — molecules from cannabis.
There are benefits to doing so, Anido told IBD. When a biotech stock uses the cannabis plant, it must extract the oil and then purify it, adding time and complicating the process. By using molecules created in a lab, Zynerba ensures its CBD is 99.9% pure.
CBD is one of two well-known molecules found in cannabis. The other is tetrahydrocannabinol, or THC. THC is responsible for the euphoric high associated with marijuana. Patients using a CBD oil or gel — like Epidiolex from GW Pharma or Zynerba's experimental medicine — want assurance it's pure.
But that's not always the case, Anido says. In a September 2018 article, Forensic Science International wrote about a study of nine CBD e-liquids used in e-cigarettes. They were from a single maker of cannabinoids and other psychoactive compounds. The website for the products claimed they were 100% CBD extracts.
In the study, however, researchers found two of the nine e-liquids contained THC. Four of the nine contained another lesser-known cannabinoid. One contained dextromethorphan, used in cold medicines with the potential to cause hallucinations at high doses.
Understanding FDA On Cannabis
This isn't the case for FDA-approved products, Anido says. Zynerba is testing a 250-milligram to 500-milligram CBD gel for Fragile X syndrome, a genetic condition that can lead to learning disabilities and cognitive impairment. That dose would be fairly expensive at a dispensary, he says.
"Today, in the medical marijuana space, it's all over the place," he said. "What you may get this week from a dispensary is probably different than what you're going to get a month from now when you come back in order to get some additional product."
In this vein, cannabis medicine remains like any other class of drugs regulated by the FDA. Biotech stocks and Big Pharma companies must develop stringent clinical studies, GW Pharma's Schultz says. The goal is to ensure a patient gets exactly the same amount of medicine every time, he says.
"The medicine is fully characterized for safety through well-controlled studies, which is what physicians rely on as they utilize the medicine in their patient population," he told IBD. "What we're doing is very different from the dispensary approach."
Biotech Stocks Aim For CBD, THC Drugs
Most cannabis medicine companies seem to be doing research today in CBD. Some examine the impact of cannabis medicine on cannabinoid receptors known as CB1 and CB2. The body uses these in processes like appetite, pain, mood and memory.
Corbus Pharma's lead cannabis medicine would bind to an agonist of CB2. An agonist initiates a physiological response when combined with sensors in the body. The biotech stock's goal is to ameliorate chronic inflammation and fibrotic problems. It's also testing a CB1 drug that could have a use in several fibrotic conditions.
Fellow biotech stock Cara is working on a cannabinoid receptor agonist in preclinical development for neuropathic pain.
Insys has an approved cannabis medicine — created synthetically — to treat anorexia in patients with AIDS and to ease nausea caused by anti-cancer medicine chemotherapy. AbbVie's Marinol has the same purpose. Both contain THC.
The DEA treats cannabis medicines — those derived from a plant and those created in a lab — differently from the plant itself. Epidiolex is a Schedule 5 drug. Marinol is a Schedule 3 drug. Both have a lower potential for abuse than cannabis itself, the DEA says.
Will DEA Relax Its Stance On Cannabis?
Miracle Mile's Sterz expects the DEA to "relax" its stance on cannabis medicine over time.
"Primarily because most of this is not new science," he said. "There's putting it into a new format, but this is not a new space like maybe CRISPR technology or CAR-T or some of these other new technologies that are really coming into their own."
Julie Raque, vice president of marketing for Cannabistry Labs, says the U.S. has reached "critical mass" in terms of Americans approving marijuana use across the board. Cannabistry Labs is a research and development firm for cannabis-infused products.
Raque offers several examples of the swing in public opinion for cannabis. Congress recently passed the Farm Bill, legalizing industrial hemp, a boon for the CBD oil industry. Canada legalized cannabis for recreational and medicinal purposes. The approval of Epidiolex only helps that effort, she told IBD.
"The approval of this was eye-opening for everyone on the pharmaceutical side who saw that this was outside of the molecules and the type of engineering that goes on in their traditional research and development," she said. "This plant is so unique with a myriad of therapeutic abilities."
There's Big Money In Cannabis Medicine
Miracle Mile's Sterz expects Big Pharma to get into cannabis medicine in a big way. Many Big Pharma companies are experiencing generic rivalries for some of their mature medicines.
He expects Big Pharma companies to acquire biotech stocks with promising cannabis drugs to help diversify.
"Keep an eye on what's coming out of the mouths of major pharma," he said. "I think that will be your indication. Once one gets bought, they'll all get bought."
There's a lot of money in cannabis medicine, says Katexco Pharmaceuticals Chief Executive Jonathan Rothbard. Katexco, a private company, is the brainchild of Rothbard and Lawrence Steinman, both members of the Steinman Lab at Stanford University.
Katexco is investigating cannabis medicine in inflammation. But Rothbard sees a big future for cannabis medicine in treating pain. He says it could reduce demand for highly addictive painkillers now on the market. The National Institute on Drug Abuse says more than 115 people die of opioid overdoses daily in the U.S.
Could Cannabis Medicine Replace Opioids?
Cannabis medicine could help change that paradigm, Rothbard says. Globally, the opioid market will reach nearly $35 billion by 2025, according to Grand View Research.
"I think they're going to be a fantastic substitute for opioids in pain relief," Rothbard told IBD. "Ten years from now, no one will be using opioids other than those patients directly out of the operating room. Then, they will be switched to (activators) of CB1 or CB2."
Opioids are highly addictive. But that's not a problem with cannabis, he says.
"Patients (on opioids) reach a dose at which it starts affecting the heart," he said. "That will never happen with a cannabis-based drug, because the wiring of the signaling in the brain is fundamentally diff
I'm ready to hear about a JV for our safe skin cream in Czech and EU. Get product on the shelf and generate some sales and revenue....NOW!
Total RNA Sequencing
Legislation Introduced in House to Repeal the PTAB and the AIA
http://www.ipwatchdog.com/2018/07/17/legislation-house-repeal-ptab-aia/id=99059/
by Steve Brachmann
July 17, 2018
On June 28th, Congressman Thomas Massie (R-KY) introduced a bill into the House of Representatives known as the Restoring American Leadership in Innovation Act of 2018 (H.R. 6264). The bill, which is co-sponsored by Congresswoman Marcy Kaptur (D-OH) and Congressman Dana Rohrabacher (R-CA), would go a long way in rectifying the tremendous damage which has been wrecking the U.S. patent system in the years since the passage of the America Invents Act (AIA) of 2011.
There are 13 sections to Massie’s bill, many of which are geared towards the abolition of various statutes of the AIA. Perhaps the most salient portion of the proposed bill are sections regarding the abolishment of the Patent Trial and Appeal Board (PTAB) as well as the elimination of both inter partes review (IPR) and post-grant review (PGR) proceedings currently conducted by the PTAB. As the bill states, both IPR and PGR proceedings “have harmed the progress of science and the useful arts by subjecting inventors to serial challenges to patents.” The bill also recognizes that those proceedings have been invalidating patents at an unreasonably high rate and that patent rights should adjudicated in a judicial proceeding and not in the unfair adjudication proceedings which occur within the U.S. Patent and Trademark Office. Ex parte reexamination proceedings would be preserved by this bill as well.
The section of the bill that would abolish the PTAB would re-establish the Board of Patent Appeals and Interferences (BPAI), the agency which had existed within the USPTO prior to passage of the AIA. The BPAI would be directed to hear appeals from patent applicants as well as hold interference proceedings to determine priority and patentability of inventions which are claimed in U.S. patent applications. With the removal of IPR and PGR proceedings, the bill notes that the PTAB is no longer needed to conduct those proceedings. Outside of the context of ex parte reexamination proceedings, the BPAI wouldn’t be used to invalidate a patent which has issued.
Another aspect of the AIA that would be repealed through passage of the Restoring American Leadership in Innovation Act is the first-to-file provision, returning the U.S. patent system to a first-to-invent system. The bill would also restore the one-year grace period that an inventor had prior to the AIA, allowing the inventor a full year before being compelled to file a patent application to cover his or her invention. This grace period enables an inventor more time to attract investment, conduct research and development and perfect the invention to improve the quality of the patent application that is eventually filed. The bill would also roll back the AIA’s best mode requirement which required an inventor to describe the “preferred embodiment” of an invention, which only served to limit what an inventor could claim as his or her invention.
This bill would also clear up the legal morass surrounding the patentability of certain types of inventions which has been created in recent years by U.S. Supreme Court decisions in cases like Alice and Mayo. It would amend 35 U.S.C. § 101, the statute governing the basic threshold for the patentability of inventions, such that any new and useful process, machine, manufacture, or composition of matter is patentable with the exception of any invention that “exists in nature independently of and prior to any human activity, or exists solely in the human mind.” The emphasis on human activity is critical for the patentability of important medical advances which have been damaged by the Supreme Court’s Mayo decision in which a diagnostic method for measuring drug metabolites to adjust the dosage of a drug was declared patent-ineligible. The language about inventions that “exist[] solely in the human mind” is clearly a reaction to Alice, where the Supreme Court declared that a computer system for completing financial transactions with the use of a third-party intermediary was patent-ineligible. This amendment to Section 101 would go a long way to restoring patentability in the personalized medicine and software fields, both of which are going to be incredibly valuable market sectors in the years to come.
Of course, Alice and Mayo are not the only places where the Supreme Court went awry and the Restoring American Leadership in Innovation Act would repeal SCOTUS’ decision in 2006’s eBay v. MercExchange, restoring injunctive relief to patent owners. Upon a finding of patent infringement, a court would presume that further infringement would cause a patent owner irreparable harm. An infringing party can overcome that presumption by presenting clear and convincing evidence that further infringement wouldn’t cause irreparable harm, but a patent owner would not be required to make or sell a product covered by the patent to show irreparable harm.
Further, Massie’s proposed bill would also undo SCOTUS’ 2017 decision in Impression Products v. Lexmark International, a case which restricted the rights of patent owners to sue for patent infringement. As the bill states, this decision has resulted in an inability of patent owners to exclude unlicensed customers from their supply chains. This particular statute is found in a section titled Restoring Patents as a Property Right and although Oil States isn’t directly referenced, this section would provide much needed relief to the court’s pronouncement of patents as public franchises. The bill would change U.S. patent code to say that “patents shall be recognized as private property rights” and further recognizes that patents are freely transferable as property through either assignment or licensing.
The bill, if passed, would also accomplish other goals for which supporters of the U.S. patent system have been asking for some time. Fee diversion at the USPTO would be eliminated by establishing a revolving fund for the agency at the U.S. Treasury. 35 U.S.C. § 102, which governs conditions of patentability based on novelty, would be amended so that information disclosed to the USPTO through patent applications aren’t considered prior art that could preclude the issuance of a patent. The automatic publishing of patent applications by the USPTO would be abolished, preventing the release of any information until a patent issues. The presumption of validity of a patent issued by the USPTO would also be restored and the bill would provide the presumption of validity for each individual claim of a patent independent of other claims, even if the claim is dependent upon another claim which has been declared invalid.
This bill, as written, is currently America’s best hope to restore sanity and prosperity to the U.S. patent system. It directly addresses issues with patentability of inventions and the patent opposition system which have been key weaknesses contributing to the demise of the nation’s system in international rankings and cited by the U.S. Chamber of Commerce in its recent 12th-place ranking for the United States’ patent system. No doubt this bill will be besieged by the usual cadre of well-financed Silicon Valley allies who worked so hard to get the AIA passed in the first place. Anyone who cares about the future of American innovation should get on the phone as soon as possible and call upon their Representative to support H.R. 6264 and stand up to the efficient infringer cabal which has turned the U.S. patent system into a shipwreck.
Unfortunately, I do not think he was talking about penny stocks. My account has additional shares after end of day trade yesterday. GL
The Spark of Life Club Program
https://dementiacareinternational.com/spark-life-philosophy/
Spark of Life Philosophy is a way of being with the highest intent to lift the spirit, awaken dormant abilities and heal relationships. The focus is on How to connect, How to communicate and How to care. The aim is to foster kindness, compassion, empathy, respect and an attitude of unconditional love.
The philosophy is about redefining what it means to have dementia, opening up new possibilities for improvement. It is also about revitalising the culture of care, enriching the quality of life for people with dementia and giving joy and renewed energy to carers.
Still accumulating shares. Curious, is anyone else concerned of a hostile takeover? It's always a risk when there's no shareholder protection..poison pill etc. especially w/ pennies. Thoughts appreciated, thanks!
What is Liquid Biopsy?
A liquid biopsy is a simple and non-invasive alternative to surgical biopsies which enables doctors to discover a range of information about a tumour through a simple blood sample. Traces of the cancer’s DNA in the blood can give clues about which treatments are most likely to work for that patient.
Tolerability and convenience are a major boost for patients. The biggest benefit lies in the potential of liquid biopsies to detect disease progression or treatment resistance long before it would trigger clinical symptoms or appear on imaging scans.
Most cancers have multiple genetic mutations and they may not have the same ones in all parts of the cancer. The tissue samples removed for biopsy may not show all mutations whereas liquid biopsies offer an improved chance of detecting these genetic changes.
“Liquid biopsies could be a game-changer in cancer testing,” said Miro Venturi, Roche’s Global Head of Diagnostics Biomarkers. “In terms of patient acceptability and disease management, the benefits of non-invasive, quick and easily repeatable tests are clear. And in the longer term, liquid biopsies may ultimately be used to catch signs of cancer early, before symptoms arise. This could make a significant difference to the way we understand and treat cancer.”
https://www.roche.com/research_and_development/what_we_are_working_on/oncology/liquid-biopsy.htm
raja- Thanks for the recent article on exosomal tau and biomarkers.
This is interesting:
" The tau protein has long been implicated in Alzheimer's, however, tau occurs as a family of related molecules which have subtly different properties. "
Here's a study reference on CTE and tau exosomes. "TauSome™, an exosomal biomarker that may be the first non-invasive candidate to detect Chronic Traumatic Encephalopathy (CTE) in living individuals". Nano Liquid Biopsy for CNS and Cancer is now in play. imo
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad151028?resultNumber=7&totalResults=48&start=0&q=exosome&resultsPageSize=10&rows=10
Does anyone have an explanation?
You mind explaining the WHO Registry for PDD trial. My confusion has to do with date of first enrollment. Any clarification is appreciated.
http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2017-004335-36-ES
Thank You, Zena.
You mind explaining the WHO Registry for PDD trial. My confusion has to do with date of first enrollment. Any clarification is appreciated.
http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2017-004335-36-ES
Can you provide a link, please?
Welcome to Dementia Care International
https://dementiacareinternational.com/
Scroll down and click for a very Heart Warming video. Good work going on down under, spreading around the world.
A word of appreciation and thanks to all Veterans for your sacrifice and service to our country. God Bless You All!
The registration data on WHO indicating first enrollment of 07/04/18 is possible given the (AEMPS) Approved: July 4, 2018.
Would Anavex have been the one responsible for filling that part out?
The WHO posted PDD registration shows date of first enrolment: 04/07/2018.
http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2017-004335-36-ES
The link to EU Clinical Trials Register shows Start date of 2018-07-04
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004335-36
Anavex 10/30/2018 PR announced, "that it has enrolled the first patient."
https://www.anavex.com/first-patient-enrolled-in-anavex-life-sciences-phase-2-clinical-trial-of-anavex2-73-for-the-treatment-of-parkinsons-disease-dementia-pdd/
Did enrollment start earlier in the year and Anavex withheld the PR then released it in October?
PDD Registration
Midterms 2018: The states considering legalising marijuana on election day
Joe Sommerlad,The Independent 41 minutes ago .
American voters heading to the polls for the midterm elections will be deciding on more than just their pick of lawmakers at the ballot box on Tuesday.
In addition to choosing senators and state governors – and therein determining whether the Republicans or Democrats hold a controlling majority in the Senate and House of Representatives – the electorate are also voting on crucial matters of policy at a state level.
In Idaho, Utah and Nebraska, for instance, voters will decide whether to extend Medicaid. In West Virginia, Oregon and Alabama, access to abortion will be under the microscope.
:: Follow the latest on today’s events on our US midterms liveblog
The legalisation of marijuana is also up for debate, one of the most divisive topics in the current American political landscape.
Despite cannabis being the subject of a federal prohibition, nine states and the District of Columbia all now permit its recreational use while 30 allow its administering on medical grounds.
On Tuesday, North Dakota and Michigan will decide whether to permit recreational use while Missouri and Utah will ask voters whether the drug should play a role in healthcare.
In North Dakota, Measure 3 sets a minimum purchase age of 21, erases pot convictions from criminal records and adds new penalties for those found selling it to minors.
In Michigan, Proposal 1 sets an age limit of 21, compels the state to establish a licensing system for growers and sellers, allows local businesses to prohibit its consumption on their premises and places a 10 per cent sales tax on cannabis.
In Missouri, the new proposal would change the state's constitution to make it harder to change marijuana laws in future and similarly prompt the state to build a regulatory system.
In Utah, Proposition 2 will make it legal for sufferers to access pot but not in a smokable or edible form or to grow their own supply at home.
The increasing liberalisation of attitudes towards marijuana, typically in left-leaning states, is grounded in research suggesting it can be used to soothe a range of ailments and complaints, from chronic muscle pain or nausea during cancer treatment to relieving the symptoms of glaucoma, Crohn’s disease, Parkinson’s, multiple sclerosis and childhood epilepsy.
Democrat Beto O’Rourke, running against Ted Cruz for the Texas Senate, is one of the most high-profile liberal candidates to have called for decriminalisation during the current campaign season.
An unofficial lobbying day known as “420” – started by a group of Grateful Dead fans in California in the 1970s – takes place on 20 April every year to call for the wider acceptance of weed.
Arkansas, California, Florida, Massachusetts, Nevada and North Dakota all increased access to marijuana in 2016, a watershed year for the issue.
Internationally, Uruguay became the first country in the world to completely legalise recreational marijuana in 2017 but Canada recently voted to follow suit, prompting speculation that other western nations could do the same.
https://www.yahoo.com/news/midterms-2018-states-considering-legalising-141644729.html
Saturday, October 27- Oral communications - Jeffrey Lee Cummings, MD4, Paul S. Aisen, MD1
1.45 - 2.00 p.m.
OC31 - TRC-PAD: Accelerating participant recruitment in AD clinical trials through innovation
Gustavo A. Jimenez-Maggiora, MBA1, Rema Raman, PhD1, Michael S. Rafii, MD, PhD1, Reisa Anne Sperling, MD2,3, Jeffrey Lee Cummings, MD4, Paul S. Aisen, MD1
The capture and removal of AZ derived exosomes will play a central role in an effective treatment for AD. A2-73 will work in conjunction with the hemopurifier.
I appreciate all the great contributions to this thread. Thank you All!
Drugmakers' Free Services Spur Government Scrutiny
09/21/2018 | 08:15am EDT
By Peter Loftus
Senescence and Exosomes
Abstract
Senescence is a cellular phenotype characterized by an irreversible cell cycle arrest and the secretion of inflammatory proteins, denominated senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behavior of neighboring cells and altering the microenvironment; yet, until now this role has been mainly attributed to soluble factors. Here, we report that extracellular vesicles also alter the environment by transmitting the senescent phenotype to other cells via exosomes (extracellular vesicles of endocytic origin). A combination of functional assays, Cre-loxP reporter systems, proteomic analysis and RNAi screens confirm that exosomes form part of the senescent secretome and mediate paracrine senescence via the activation of a non-canonical interferon (IFN) pathway. Altogether, we speculate that exosomes could be drivers of tissue degeneration both locally and systemically during aging and age- related disease.
https://www.biorxiv.org/content/early/2018/06/27/356238
Agreed. AVXL is doing best by setting up trials outside the US.
I hold shares in a medical device company that received BTD in October of last year. Final guidance was due out that December. Long story short, it has yet to happen.
Communication between the company and FDA has been very open and active this whole year(per CEO). Then, on the latest CC the CEO said they were informed by the FDA a few weeks back that Final Guidance/provisions must me issued in order to move forward.
The company was clueless up until that point.
Something STINKS out there in FDA land.
No mention of Anavex. Thought it was interesting that his CNS timeline listed Rett Syndrome in 2020. At the time, I just sorta chuckled..but here we are approaching 2019. He did nail Axovant flop, so got to give him that much.
https://definedhealth.com/surfing-the-cns-pipeline-ripples-swells-or-waves/
Harry Tracy, of NI Research, and Defined Health get together on CNS via webinar.
Harry was involved in a conference that Anavex was also a part in 2017. The presentation shows potential Rett approval in 2020 (?). It's worth a listen, imo.
Also talks about Axovant and their (recycled)loser drug before it failed.
Webinar was Q2 2017.
This is the first study I've seen showing exosomes role in the neuron-to-neuron transfer of amyloid in AD patients' brains. What role might A2 73 play in this process, if any?
No, this paper was published from a study in Sweden, n=10.
Alzheimer’s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers
Acta Neuropathologica
July 2018, Volume 136, Issue 1, pp 41–56| Cite as
Abstract
The gradual deterioration of cognitive functions in Alzheimer’s disease is paralleled by a hierarchical progression of amyloid-beta and tau brain pathology. Recent findings indicate that toxic oligomers of amyloid-beta may cause propagation of pathology in a prion-like manner, although the underlying mechanisms are incompletely understood. Here we show that small extracellular vesicles, exosomes, from Alzheimer patients’ brains contain increased levels of amyloid-beta oligomers and can act as vehicles for the neuron-to-neuron transfer of such toxic species in recipient neurons in culture. Moreover, blocking the formation, secretion or uptake of exosomes was found to reduce both the spread of oligomers and the related toxicity. Taken together, our results imply that exosomes are centrally involved in Alzheimer’s disease and that they could serve as targets for development of new diagnostic and therapeutic principles.
https://link.springer.com/article/10.1007/s00401-018-1868-1
Possible reason for Rett delay? New model testing?
Tsix–Mecp2 female mouse model for Rett syndrome reveals that low-level MECP2 expression extends life and improves neuromotor function
Lieselot L. G. Carrette, Roy Blum, Weiyuan Ma, Raymond J. Kelleher III, and Jeannie T. Lee
PNAS July 23, 2018. 201800931; published ahead of print July 23, 2018. https://doi.org/10.1073/pnas.1800931115
Significance
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in MECP2. To treat RTT, reactivating the dormant copy of MECP2 on the inactive X has been of considerable interest. Although potential therapeutics have been identified, their development has been hampered by the lack of a suitable female mouse model and uncertainty regarding how much MECP2 needs to be restored. Here, we create a female model with a more severe phenotype, including a short lifespan, neuromotor impairment, and repetitive behaviors often seen in human RTT. Significantly, 5–10% MECP2 restoration in brain extends lifespan by eightfold and improves RTT phenotypes. Our study thus provides a much-needed female model and implies potential therapeutic benefit with low-level MECP2 expression.
Abstract
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by a mutation in the X-linked methyl-CpG-binding protein 2 (MECP2). There is currently no disease-specific treatment, but MECP2 restoration through reactivation of the inactive X (Xi) has been of considerable interest. Progress toward an Xi-reactivation therapy has been hampered by a lack of suitable female mouse models. Because of cellular mosaicism due to random X-chromosome inactivation (XCI), Mecp2+/- heterozygous females develop only mild RTT. Here, we create an improved female mouse model by introducing a mutation in Tsix, the antisense regulator of XCI allelic choice. Tsix–Mecp2 mice show reduced MECP2 mosaicism and closely phenocopy the severely affected Mecp2-null males. Tsix–Mecp2 females demonstrate shortened lifespan, motor weakness, tremors, and gait disturbance. Intriguingly, they also exhibit repetitive behaviors, as is often seen in human RTT, including excessive grooming and biting that result in self-injury. With a Tsix allelic series, we vary MECP2 levels in brain and demonstrate a direct, but nonlinear correlation between MECP2 levels and phenotypic improvement. As little as 5–10% MECP2 restoration improves neuromotor function and extends lifespan five- to eightfold. Our study thus guides future pharmacological strategies and suggests that partial MECP2 restoration could have disproportionate therapeutic benefit.
Contributed by Jeannie T. Lee, June 20, 2018 (sent for review January 17, 2018; reviewed by Michela Fagiolini and Monica J. Justice)
http://www.pnas.org/content/early/2018/07/17/1800931115
Thanks for the link, TTT.
1 hour ago
Be wary of Alzheimer’s breakthroughs
https://www.axios.com/alzheimers-disease-breakthroughs-medicine-ban2401-f4ab58fd-f195-4fcf-8212-d2a51737f175.html
25 July 2018
GSK and 23andMe sign agreement to leverage genetic insights for the development of novel medicines
Issued: Wednesday 25 July 2018 London UK and Mountain View, CA
If OWCP is thinking about uplisting then a Reverse Split is a real possibility given current pps. Holding what I have but will wait this out on any add. GL
Added some more yesterday. Hope the company is not thinking reverse split.