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Quintiles Inks 5-Year Deal With NFL To Track Injury Data in Forbes, 2/12/2015
Excerpts:
"Quintiles, the world’s largest biopharmaceutical contract services company, announced on Tuesday a five-year extension of their relationship with the National Football League in tracking of athletic injuries and identifying trends potentially associated with their causes.
The company’s epidemiology group had already been working with the NFL since 2011 when it piloted an injury surveillance system.
Christina Mack, MPH, PhD, associate director of epidemiology at Quintiles, said that the expanded five-year program builds on the convergence of their data collection and analytics with the NFL’s adoption of an electronic medical records (EMR) system instituted for the 2014-15 season with the NFL Players Association.
“Part of the expansion of services and as well as the time we’ve contracted with the NFL is around the use of the EMR,” said Mack."
"“This entire program has been focused on understanding the patterns of occurrence of injuries to players. We look at preseason, regular season and post-season, in practices as well as games, said Nancy Dreyer, MPH, PhD, senior vice president and global head of scientific affairs at Quintiles"
"“The question is, ‘Are there changes that can be made to promote player health?,’” said Dreyer."
"However, the league announced in 2013 that teams contributed $30 million to the National Institutes of Health for brain injury research. Moreover, the league committed an additional $100 million to medical research in the 2013 collective bargaining agreement with the players association."
Article at:
http://www.forbes.com/sites/davidkroll/2015/02/12/quintiles-inks-5-year-deal-with-nfl-to-track-injury-data/
Ultrasound technique shown to reverse Alzheimer’s symptoms in mice IN Gizmag, Nick Lavars, February 12, 2015
Excerpt:
"Magnetic resonance (MR) imaging-guided ultrasound, a technology that involves highly-targeted ultrasound beams and monitoring their effects through imaging, has shown to help treat symptoms of Alzheimer’s disease in mice. The treatment was found to improve brain performance in the animals and has the researchers hopeful that the technique may prove effective in improving cognitive behavior in humans"
"Using this technique to treat the transgenic mice, they observed improvements in cognition and spatial learning. They say a possible reason for this is a boost in neuronal plasticity resulting from the ultrasound beam, combined with a reduction of brain plaque, the presence of which in humans correlates with symptoms of Alzheimer’s. The team also reported an increase in the number of neurons and dendrite length, the tree-like extensions of neurons that help them communicate with other neurons.
"The results are an exciting step in the search for Alzheimer’s treatments," says Steven Krosnick, Program Director for Image-Guided Interventions at the National Institute of Biomedical Imaging and Bioengineering at Nation Institutes of Health. "But there is more to be done. There are limitations on the memory tests that can be done on mice, and human cognition is significantly more complex. Hopefully these results will open doors to more research on how MR imaging-guided focused ultrasound could benefit cognition and perhaps be magnified by using other therapeutics in conjunction with this method."
Article at:
http://www.gizmag.com/ultrasound-alzheimers-mice/36071/?utm_source=Gizmag+Subscribers&utm_campaign=61a54c93bd-UA-2235360-4&utm_medium=email&utm_term=0_65b67362bd-61a54c93bd-76708937
Alzheimer's investigators open a new front in BACE1 war in Fierce Biotech Research, January 19, 2015 | By John Carroll
Article:
"The cleaving action of the BACE1 enzyme is considered one of the essential steps in creating concentrations of amyloid beta, the toxic proteins found in the brains of Alzheimer's patients. And as a result, as the leading amyloid beta programs foundered in late-stage studies, BACE1 became a prime target in the research community, with Merck leading the way in the clinic with a late-stage therapy.
The problem with BACE1, though, is that it plays a number of roles, some needed for the healthy working of the human body, and a range of early-stage programs has triggered some nasty side effects. But now scientists at the RIKEN-Max Planck Joint Research Center in Japan say that they may have found a new way to tackle BACE1 while avoiding the side effects.
Researchers led by Yasuhiko Kizuka, Shinobu Kitazume, and Naoyuki Taniguchi at RIKEN, in collaboration with Tamao Endo and Shigeo Murayama at the Tokyo Metropolitan Institute of Gerontology, say that the enzyme GnT-III plays a key role in attaching a sugar to BACE1 in the brain. Eliminating the sugar prevented the cleaving by repositioning BACE1, and in hybrid mouse models the investigators say they got the desired reduction in amyloid beta along with improvements in cognition.
Because the process is "highly selective," they add, they were able to do that without knocking out BACE1's role in unrelated functions, preventing the quick death that afflicts rodents when you simply knock out BACE1. That makes GnT-III a good target for Alzheimer's, which they've begun screening for. And it raises the role of glycosylation, the modification of proteins by sugars, to a new level of importance in drug research.
"Although a sugar change is often considered just a marker for disease or a specific cell type, our team has clearly demonstrated the functional role of a glycan during AD development," says Yasuhiko Kizuka. He added that "this work offers a good opportunity for many AD researchers to reconsider the importance of glycosylation."
Article at:
http://www.fiercebiotechresearch.com/story/alzheimers-investigators-open-new-front-bace1-war/2015-01-19
Reference work done by Mullan/Crawford in 2011 before:
Anatabine lowers Alzheimer's Aß production in vitro and in vivo.
Paris D1, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M.
Excerpt:
" Since NF?B is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aß production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the Aß lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble Aß1?40 and Aß1?42 levels in a transgenic mouse model of Alzheimer's disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain Aß accumulation."
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/21958873
Neuroscience project tries to put the immune system to work against Alzheimer's in Fierce Biotech Research, February 10, 2015 | By John Carroll
My comments: Contact RCPI
Excerpts:
"Neurogeneticists at the University of Southern California say that they were able to use immune cells to clear away amyloid beta, the toxic protein that may be the cause of Alzheimer's.
The team reports that they were able to spur the immune response by blocking interleukin-10, demonstrating the principle in a mouse study in which rodents displayed improved cognitive ability following treatment. Now they plan to take their work another step forward using genetically modified rats to create a model for the disease.
Terrence Town
"Our study shows that 'rebalancing' the immune response to wipe away toxic plaques from the brain may bring new hope for a safe and effective treatment for this devastating illness of the mind," said Terrence Town, a professor of physiology and biophysics at the Keck School of Medicine of USC and the study's senior author.
Or not. There's no shortage of successful animal studies related to amyloid beta and Alzheimer's. But there is a clear shortage of clinical evidence that the amyloid beta approach actually works in humans. A series of late-stage failures has pointed more researchers down the path of early-stage disease work, theorizing that once the brain is damaged by toxic proteins reversing that damage may be beyond anyone's control.
Article at:
http://www.fiercebiotechresearch.com/story/neuroscience-project-tries-put-immune-system-work-against-alzheimers/2015-02-10
Certain Allergy, Depression Meds Tied to Higher Odds for Dementia
Class of drugs interferes with a key brain chemical in Web MD, Robert Preidt, January 26, 2015
Excerpts:
" Long-term and/or high-dose use of a class of medications used for hay fever, depression and other ills has been linked in a new study to a higher risk of dementia.
The drugs -- called anticholinergics -- include nonprescription diphenhydramine (Benadryl) and tricyclic antidepressants like doxepin (Sinequan). This class of medications also includes older antihistamines like chlorpheniramine (Chlor-Trimeton) and "antimuscarinic" drugs for bladder control, such as oxybutynin (Ditropan).
However, the study could only point to an association between long-term or high-dose use of these drugs and a higher risk of dementia, it could not prove cause-and-effect.
Also, the relationship "did not occur at the lowest dosage range but did occur at higher dosages used long-term," said one expert, Dr. Alan Manevitz, a clinical psychiatrist at Lenox Hill Hospital in New York City. He was not involved in the new study.
Manevitz also stressed that consumers "should not abruptly stop any current medication treatment but rather should first consult with their physician."
The new study was led by Shelly Gray of the Group Health Research Institute-University of Washington. Her team explained that the anticholinergic class of medications work by blocking a neurochemical called acetylcholine, in both the brain and body.
Manevitz noted that people "suffering from Alzheimer's disease typically show a marked shortage of acetylcholine."
Article at:
http://www.webmd.com/alzheimers/news/20150126/use-of-certain-allergy-depression-meds-tied-to-higher-odds-for-dementia
Sugar industry's attempt to influence public health policy is 'a major issue' in Medical News Today, David McNamee, 13 February 2015
Excerpts:
"An investigative report from The BMJ claims to expose "extensive links" - going much deeper than previously known - between public health scientists and the sugar industry."
"Across the four-part investigation, Jonathan Gornell reports evidence of a government committee working on nutritional advice receiving funding from companies whose products are considered by many to be responsible for the ongoing obesity crisis.
The BMJ claim that the report raises "important questions about the potential for bias and conflict of interest among public health experts."
Members of the Scientific Advisory Committee on Nutrition and the Medical Research Council's Human Nutrition Research unit (HNR) were found to have received funding from sugar giants including Coca-Cola, Mars, Nestlé, Sainsbury's, the Institute of Brewing and Distilling and Weight Watchers International, among others.
The extent of these donations was found to be unprecedented, with one former HNR researcher - Susan Jebb, professor of diet and population health at the University of Oxford and chair of the British government's Responsibility Deal Food Network - accepting funding worth $2.10 million from companies such as Coca-Cola between 2004 and 2015.
As principal investigator, Jebb also received a donation of $297,000 from Coca-Cola to one study she was working on.
Some of the companies who invested in Jebb's research - including Unilever and Coca-Cola - are now members of the government's Responsibility Deal, which she chairs. Under the deal, the sugar industry pledges to a government target of a national 5% reduction in calorie consumption.
However, the new report states that companies have not upheld this pledge and the initiative has been ineffective, with a calorie increase of almost 12% in the national weekly shop during 2006-14.
According to Gornell, a core issue is the paucity of public research funding. The UK government instead encourages its public research organizations to seek commercial funding, making researchers vulnerable to accusations of conflicts of interest:
He elaborated:
"Public health is the business of government, and not the business of big business. Industry's legal obligation is to its shareholders, for whom it must make as much money as possible. If it can do that while striking a socially responsible pose, it will do so, but when the bottom line is under threat, social responsibility is exposed as a tokenistic charade."
Gornell's report references research that has found evidence of pro-industry bias in some sponsored studies. However, he says that the main concern of the research was "the general principle" rather than documenting bias in specific papers:
"How can it be right for a researcher attempting to establish whether or not ingredient X is harmful to accept funding to do so from the manufacturer of ingredient X? Would society consider it acceptable if the salary or expenses of a judge ruling on a legal dispute were paid by one of the parties?"
Article at:
http://www.medicalnewstoday.com/articles/289323.php
Four retailers pull some dietary aids off shelves after probe in Fox News, Published February 12, 2015Reuters
Excerpt:
"Walgreens Boots Alliance Inc, Wal-Mart Stores Inc, GNC Holdings Inc and Target Corp agreed to remove certain dietary supplements off their shelves in New York after receiving a threat of legal action from the state's attorney general, the New York Times reported.
The retailers received subpoenas from New York State attorney general Eric Schneiderman on Wednesday, demanding evidence for the health claims printed on labels of dietary supplements sold in New York, the newspaper said.
Last week, Schneiderman asked major retailers to halt sales of certain herbal supplements as DNA tests failed to detect plant materials listed on majority of products tested. (on.ny.gov/1BSm53a)
Earlier this week, GNC said it refuted the claims made by Schneiderman in his Feb. 2 letter and said retesting results clearly and conclusively demonstrate that the company's products are pure, properly labeled and in full compliance with all regulatory requirements."
Article at:
http://www.foxnews.com/health/2015/02/12/four-retailers-pull-some-dietary-aids-off-shelves-after-probe/
Pharma Companies Switch Gears: A New Market Emerges Called 'The Fountain Of Youth' in Forbes, This article was written with contribution from Aishwarya Vivekanandan, Industry Analyst with Frost & Sullivan’s global Healthcare and Life Sciences practice., 2/12/2015
Excerpts:
"Botox was the first product to change the face of women and even men in the last decade. Today we are seeing a whole suite of companies coming up with pharmaceutical magic potions to keep people feeling and looking young forever. The search for a magical elixir to prolong life does not seem to be all that “magical” and impossible with our current technology. A host of companies from Novartis to Google GOOGL +1.51% are on a mission to conquer aging.
Imagine living 10 years more than your expected lifespan, feeling a few decades younger than your actual age, and having the mental and physical agility of someone half your age. Who wouldn’t want that? There is increasing evidence that our current biomedical science is capable of extending human life by approximately 10 years. And many companies are swarming to focus on this magic potion. When GlaxoSmithKline shelled out close to $720 million on Sirtris Pharmaceuticals, which said its drug could combat aging, the game was on. Even though this acquisition failed miserably, it started a race to create an anti-aging drug by large pharmaceuticals and young biotech companies like Google’s Calico. Calico has partnered with another pharma giant, AbbVie ABBV +0.64%, and is on a mission to reverse engineer the biology that controls lifespan and allow humans to prolong healthy lives with its $500 million investment into this project."
"Currently, there are already over 100 drugs that have been found to combat aging. One such compound that achieved prominence in aging-related science was reservatrol. Reservatrol is the reason why many doctors encourage drinking red wine. Reservatrol activates an enzyme that is said to slow aging. Therefore, many pharmaceuticals saw this as a potential drug, like Sirtris. Although the effects of resveratrol in rodents have shown significant improvements, questions have emerged surrounding the effectiveness on humans. In recent years, another compound, rapamycin (TOR) kinase, has emerged as a key pathway that mediates life span extension.
One such company at the forefront of this research is Novartis. Novartis’s drug is a form of rapamycin, a compound that blocks genetic pathways that cause aging. According to its research with 200 volunteers who received the rapamycin treatment for a period of weeks, there was a 20% stronger immune response when the flu vaccine was administered. Although this drug will not be available for commercialization for at least 10 years, the potential for a viable product could create a new segment in the anti-aging market."
"Now that living beyond age 100 can become a reality, we need to start looking at the implications of this progress. What would this mean for our society and, more importantly, to healthcare systems that are already under crises? The current trend of the aging population fueling medical costs will reverse. There is hope that with this preventative model of healthcare, costs will decline as people remain healthy as they grow older. But this delayed aging will also mean more people draw pensions and state benefits. Our economic system will have to change dramatically to accommodate the growing workforce, which probably will work longer than ever before. It presents an enormous opportunity for new industries to flourish and bloom by targeting the aging population, which will probably become the largest segment of all population demographics in the next 20 years."
Article at:
http://www.forbes.com/sites/reenitadas/2015/02/12/pharma-companies-switch-gears-a-new-market-emerges-called-the-fountain-of-youth/2/
From previous posts, the following article reminds us of comments made about Anatabine Citrate slowing Telemorese rate decline.
From: Profiting from the “Holy Grail” of Medicine
Tuesday in Before it's News, July 12, 2011
Excerpt:
"Today, scientists have advanced the science much further. Many are now using the term “inflammaging,” coined by Claudio Franceschi, professor of immunology at the University of Bologna.
It appears that our immune systems react to the normal effects of aging as if they were injuries. This initiates inflammation, an immune response. This inflammation causes cellular stress, which increases the degree of chronic. It is, by definition, an auto-immune disorder. Some scientists call it auto[innate]immunity subclinical syndrome.
It is a vicious circle, a chronic cycle that spins faster and faster until the organism itself eventually fails. Aging, we now know, is not linear. Like so many other things, it is a process that accelerates over time.
However, if there were a way to stop chronic low-level inflammation we could put the breaks on the auto-immune inflammation cycle. If we could stop chronic low-level inflammation. Our bodies could heal naturally.
We would even see cells damaged by past inflammation-related diseases heal normally.
We’re not talking about regenerative medicine.
Regenerative medicine promises to replace aged cells and tissue with young telomere-restored cells and tissue. An alternative route is the activation of the telomerase gene, which we know can restore telomeres to youthful lengths.
In the meantime, however, we need to slow the process of telomere loss. For some time scientists have known that inflammation is the primary accelerator of telomere loss. This is why so few of us reach our theoretical maximum life spans— which could be 120 years or more.
We would be much, much more likely to reach that theoretical upper limit if we aged as we did when we were young. A drug that actually controlled inflammaging would restore the aging process to a more linear progression.
Article at:
http://beforeitsnews.com/financial-markets/2011/07/profiting-from-the-holy-grail-of-medicine-808260.html
The Coming Boom In Brain Medicines in Forbes, This story appears in the March 2, 2015 issue of Forbes.
Excerpts:
"TONY COLES COULD have had any job he wanted in the drug industry. In five years at the helm of cancer drug developer Onyx Pharmaceuticals he increased its market cap eightfold by purchasing an experimental blood cancer drug for $800 million, developing it into a big seller and flipping the whole company to Amgen AMGN +0.14% for $10.4 billion in October 2013. He personally made $60 million on the deal. Biotech watchers expected him to start another cancer company or even command a drug giant like Merck or Pfizer PFE +1.81%.
Instead, Coles, 54, is using his own money to build a Cambridge, Mass.-based startup called Yumanity that is using yeast, the microbes that help make bread and beer, to study how misfolded proteins in the brain cause Alzheimer’s, Lou Gehrig’s disease and Parkinson’s, and to create drugs based on that knowledge. There’s already interest from Big Pharma. Coles says he chose to attack brain diseases, not tumors, because the need is so dire and the science is so fresh.
“We’ve got 50 million people around the world who have these diseases, costing $650 billion a year, and lots of families like mine that have been affected,” says Coles. “I had a grandmother who died of the complications of Alzheimer’s disease. I think about my own health as well.”
"Treatments To Watch:
Here’s a look at what’s happening in five different areas of brain drug research:
DEPRESSION Outlook: Very good. Fast-acting drugs are already in late-stage trials after showing great promise. Currently: Existing drugs take weeks to have an effect. What’s next: Faster-acting drugs. Alkermes is testing one that is in late-stage trials that works in days, not weeks. A J&J inhaled derivative of ketamine and new drugs being developed by Naurex all seem to work in minutes on depression that doesn’t respond to other drugs. Long term: Eli Lilly has a new antidepressant pill that has shown some promise. Johnson & Johnson JNJ -1.93% and Lundbeck are studying how depression might be the result of misfires by the immune system that damage the brain.
MULTIPLE SCLEROSIS Outlook: Very good. Drugs may even reverse the disease. Current: Multiple sclerosis has been the neurological disease with the most advances for patients because doctors were able to discover its root cause–an overactive immune system–and focus treatments there. What’s next: More pills along the lines of Biogen Idec's BIIB +0.64% Tecfidera and Novartis' Gilenya, which keep the immune system from damaging nerves, are in development, including Forward Pharma’s FP187. Long term: The big thing to watch is whether any drug can reverse the damage the immune system does and help nerve cells regrow. One candidate is Biogen Idec’s drug known as anti-LINGO, which should show some results next year.
PARKINSON’S DISEASE Outlook: Advances coming soon, but big breakthroughs may take years. Currently: The disease, which causes shaking and loss of coordination, is treated with a synthetic drug, levodopa, that boosts levels of the brain transmitter dopamine. What’s next: Many therapies focus on what to do when levodopa wears off. Acorda Therapeutics ACOR -0.66% is developing an inhaled version. Voyager Therapeutics is testing a gene therapy that may make levodopa effective again when patients have developed resistance. Long term: Attempts by Merck, Roche and Pfizer PFE +1.81% to block a genetic mutation that can lead to Parkinson’s ran into problems when drugs caused lung damage in monkeys. Biogen Idec hopes to clear toxins that build in the brain as a result of the disease.
SCHIZOPHRENIA Outlook: Fair. Interesting drugs in development but not enough of them. Currently: Drugs can be effective at treating hallucinations and paranoia but don’t yet treat cognitive problems and social difficulties caused by the disease. What’s next: Add-on drugs. In 2016 Forum Pharmaceuticals hopes to have results on its encenicline, aimed at helping schizophrenics think more clearly. Acadia Pharmaceuticals is testing its Nuplazid to help existing antipsychotics. Long term: Intra-Cellular Therapies, a new publicly traded company, is testing a pill that, instead of working outside neurons, gets deep inside them. “It could be the most promising advance in antipsychotic pharmacology [in decades],” says Jeffrey Lieberman, psychiatrist in chief at NewYork-Presbyterian Hospital-Columbia University Medical Center.
ALZHEIMER’S DISEASE Outlook: Treatments that have a big impact are unlikely anytime soon. Currently: Industry bet big on injectable medicines to prevent or reverse Alzheimer’s by attacking the buildup of plaques in the brain–and failed. What’s next: A lower-risk approach: targeting Alzheimer’s symptoms but not trying to reverse the disease. Forum Pharmaceuticals expects results from one such drug next year. Another drug from Lundbeck is in late-stage trials. Long term: Drug companies won’t give up on the plaque approach. Biogen Idec presents data for its plaque-buster in April; Eli Lilly could release results of a big retrial of a failed drug next year; Roche is testing a plaque-buster in patients with a gene that causes Alzheimer’s before age 40. Merck, J&J and others are testing plaque-clearing pills."
Article at:
http://www.forbes.com/sites/matthewherper/2015/02/11/brain-boom-the-drug-companies-bringing-neuroscience-back-from-the-brink/
What causes brain problems after traumatic brain injury? Studies have a surprising answer: New study finds that inflammation is a major treatable cause in Eureka Alert, UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE, 15-JAN-2015
Hmmmm? Roskamp hasn't shouted loud enough?
Excerpts:
"In a perspective article published in the latest issue of Neurotherapeutics, the two authors - Alan Faden, MD, a neurologist and professor of anesthesiology, and David Loane, PhD, an assistant professor of anesthesiology, propose that chronic brain damage and neuropsychiatric problems after trauma are to a large degree caused by long-term inflammation in the brain. In their view, this inflammation is a key culprit behind the myriad symptoms that have been linked with traumatic brain injury and mild traumatic brain injury, including brain atrophy, depression and cognitive decline.
Dr. Faden and Dr. Loane also say that there has been too much emphasis on a specific diagnosis known as chronic traumatic encephalopathy (CTE), the set of symptoms and pathology that has been found in some former professional football players. They argue that this may deflect focus from other mechanisms, which may be more important and treatable. They say that although chronic traumatic encephalopathy is a serious problem, relatively few people have been diagnosed with this condition. Instead, they contend, researchers and journalists should focus more on the fact that even repeated concussive impacts or mild traumatic brain injury may trigger chronic brain inflammation that can persist for years and cause lasting damage.
"Brain inflammation is a key issue, and it has been under-emphasized," says Dr. Faden. "Recent brain imaging studies, including those in former professional football players, indicate that persistent brain inflammation after a single moderate head injury or repeated milder traumatic brain injury may be very common, and may contribute to cognitive problems. In addition, larger studies indicate that brain inflammation persists for many months or years in many people with traumatic brain injury."
The paper also points out that chronic brain inflammation related to traumatic brain injury may be treatable. Dr. Faden and Dr. Loane say recent research shows that some experimental drugs, as well as carefully controlled exercise programs, can block brain inflammation caused by traumatic brain injury. They maintain that these avenues should be pursued vigorously."
Artucke atL
http://www.eurekalert.org/pub_releases/2015-01/uoms-wcb011515.php
12th World Congress on Inflammation, August 8-12, 2015, Boston Mass.
RCPI and/or Roskamp has until April 15 to submit an abstract to participate.--So far, don't see either???
ABSTRACT TOPICS
Angiogenesis
Apoptosis
Autoimmune Diseases – RA, Psoriasis, SLE, IBD, MS
Biologic Therapies for Targeting Inflammatory and Immune Mechanisms
Biosimilars
Cachexia
Cartilage and Bone Remodeling
Cell Adhesion and Leukocyte Migration
Chemokines and Chemokine Receptors
Co-stimulatory and Co-inhibitory Pathways
Cytokines in Inflammatory Disease
Epigenetics and Regulation of the Immune Response
Fibrosis and Tissue Remodeling
Gene Therapy for Inflammatory Diseases
GPCRs in Inflammation
Immunotherapeutics
Inflammasomes in Health and Disease
Inflammation and Aging
Inflammation and Cancer
Inflammation and Metabolic Disorders
Inflammatory Cell Signaling
Inflammatory Mediators
Inflammatory Pain and Analgesia
Inflammatory Processes in Cardiovascular Diseases
Inflammatory Processes in Central Nervous System Diseases
Inflammatory Processes in Shock and Trauma
Inflammatory Responses, Stem Cells and Tissue Regeneration
Inflammatory Skin Disorders
Inhibitory Receptors and Immune Checkpoints
Innate Immunity – Macrophages, Dendritic Cells, Neutrophills, Basophils, Mast Cells, Eosinophils.
Innate Lymphoid Cells
Kinases
Lipids, their Enzymes and Inflammation
Microbiome in Health and Disease
microRNAs and lncRNAs in Inflammation (microRNAs=miRs; long non-coding RNAs=lncRNAs)
Molecular Patterns and Acute Inflammation
Mucosal Immunity
Musculoskeletal Inflammation in Health and Disease
Neutrophils, NETs and PADs
New Models of Inflammatory Mechanisms & Diseases
Novel and Innovative Platforms for Drug discovery
Novel Targets and New Drugs in Inflammation
Nuclear Hormone Receptors
Ocular Inflammation
Pattern Recognition Receptors
Proteases
Rational Drug Design for Inflammatory Targets
Resolution of Inflammation and Tissue Repair
Respiratory Disease and Inflammation
Skeletal Muscle
Small Molecule Therapeutics for Inflammatory Diseases
Systems Biology Approaches to Interrogate Inflammation
T Regulatory Cells
Tissue Damage/Repair
Toll Receptors
Transcriptional Regulation of Inflammatory and Immune Mediators
Translational Medicine and Biomarkers
Website at:
http://inflammation2015.org/2015/PROGRAM/Concurrent-Symposia.aspx
Brain's inability to repair DNA may explain dementia, memory loss in Medical News Today, Catharine Paddock PhD, 10 February 2015
ExcerotsL
"Previously, it was thought ability to repair DNA was the same throughout the body, but new research overturns this idea and shows organs vary in the extent to which they carry out a type of DNA repair called nucleotide excision repair."
"Lead investigator Jean Latimer, associate professor of pharmaceutical sciences at the College of Pharmacy at NSU, and colleagues found that the heart has the greatest ability to repair DNA using NER, followed by the gut, the kidneys, the spleen, the testes and the lungs.
However, the researchers found the brain appears to have no ability to carry out this vital type of DNA repair.
One explanation could be that because they are not exposed to light, brain cells focus their energies on more essential functions.
"Prof. Latimer says, "The human body was not designed to live past 30 or 40 years, so our brains haven't prioritized DNA repair over other necessary functions."
"Our brains are frequently not physically prepared to last as long as medical science is now allowing our bodies to live," she adds, and notes:
"These findings could help explain a root cause behind memory loss and dementia."
Article at:
http://www.medicalnewstoday.com/articles/289191.php
Study details a link between inflammation and cancer
Timing of inflammation determines whether potentially cancerous mutations may arise. in MIT News, Anne Trafton | MIT News Office,
January 15, 2015
Excerpts:
"A new study from MIT reveals one reason why people who suffer from chronic inflammatory diseases such as colitis have a higher risk of mutations that cause cancer. The researchers also found that exposure to DNA-damaging chemicals after a bout of inflammation boosts these mutations even more, further increasing cancer risk."
"“Chronic inflammation drives a lot of cancers, including pancreatic, esophageal, liver, and colon cancers,” says Engelward, who is also deputy director of the MIT Center for Environmental Health Sciences. “There are things that people with chronic inflammation could do to avoid exposures that would be problematic for them. For example, certain foods lead to DNA damage and could be avoided.”
"Inflammatory diseases such as colitis, pancreatitis, and hepatitis have been linked to greater risk for cancer of the colon, pancreas, and liver. In these chronic inflammatory diseases, immune cells produce highly reactive molecules containing oxygen and nitrogen, which can damage DNA. Inflammation also stimulates cells to divide.
Biologists had theorized that simultaneous DNA damage and cell division during inflammation could lead to cancer because dividing cells are more vulnerable to mutations caused by DNA damage. However, until recently it was difficult to test this hypothesis in animals under physiologically relevant conditions."
"When the inflammation occurred in short bursts a week or more apart, the researchers did not see any evidence of increased mutations. However, when the bouts occurred within a few days of each other, there was a significant increase in mutations."
"“That means the model that’s been around for a long time is accurate, because you do get synergy between cell division and inflammation-induced DNA damage, but in these studies there was only a mutation risk if there is chronic or repeated inflammatory responses,” Engelward says."
"“These findings suggest that chronic inflammation potentially results in increased DNA damage and proliferation that together can conspire to increase the chance of cancer formation,” says Peter McKinnon, a professor of genetics and tumor cell biology at St. Jude Children’s Research Hospital who was not part of the research team."
"This discovery suggests that people with chronic inflammatory diseases, which are common, may be more sensitive to carcinogens in the air, food and water. Also, developing fetuses and very young children may also be more sensitive to these agents because their cells are dividing more rapidly, Engelward says. Another new study from the Engelward laboratory, published in the journal Carcinogenesis, shows that animals treated with a growth-inducing hormone are more susceptible to damage-induced mutations."
Article at:
http://newsoffice.mit.edu/2015/link-between-inflammation-and-cancer-0115
How tumor-causing cells are recruited in cancers linked to chronic inflammation in Eureka Alert, For the first time, the cellular mechanisms for cancers caused by chronic inflammatory conditions are explained, providing potential therapeutic targets in the process., THE WISTAR INSTITUTE, February 9, 2015
Excerpt:
"Gabrilovich and his fellow investigators demonstrated that inflammatory conditions are associated with a specific phenotype of myeloid cells called immature granulocytic cells.
Using transgenic mice that expressed this phenotype, Gabrilovich's lab created conditions in which the granulocytic cells would accumulate in the absence of typical methods of inflammation, such as tissue damage or infection. When the mice were exposed to a tumor-promoting substance called TPA, the researchers observed a dramatic increase in the formation of benign tumors, or papillomas, usually among the first signs of the formation of skin cancer.
Gabrilovich and his team found that the granulocytic cells arrive at the skin and stimulate the migration of lymphocytes, which in turn stimulate the abnormal growth of keratinocytes, the most common type of skin cell found in the epidermis. The granulocytic cells are able to "recruit" these lymphocytes by releasing a specific factor called chemokine CCL4. This factor then recruits CD4+ T cells that produce interleukin-17 (IL-17), a proinflammatory cytokine that has already been linked to chronic inflammation and inflammatory cancers.
Through a series of steps, this study implicates that granulocytic cells accumulate and serve as the first step of tumor formation, followed by the recruitment of CD4+ T cells that produce IL-17. The combination of these events ultimately results in the development of cancer. While this study focused on skin cancer, Gabrilovich said that the study could apply to any type of cancer linked to chronic inflammation. If proven for other conditions this mechanism could open an opportunity for potential therapeutic targeting in patients with chronic inflammation that predispose a patient to cancer.
"If we are able to target these granulocytic cells directly, we may be able to prevent the inflammatory effects of IL-17, which would provide a great benefit to individuals with a high risk of developing these types of cancer," said Vinit Kumar, Ph.D., a member of the Gabrilovich laboratory and one of the co-authors of the study."
Article at:
http://www.eurekalert.org/pub_releases/2015-02/twi-htc020915.php
Study maps complete progress of MS for the first time in Medical News Today, David McNamee, 9 February 2015
Excerpt:
"In multiple sclerosis (MS), the insulating layers of nerve fibers are destroyed by chronic inflammation in the nervous system. However, the mechanisms behind the advanced stages of the disease are not fully understood, and existing treatments have a very limited effect on patients with advanced MS.
Whether MS is caused by an as-yet unidentified infectious pathogen or an autoimmune response has not yet been established. Around 2.5 million people are affected by the condition worldwide.
Prior to this new study, researchers had adopted two approaches to categorizing MS. One of these approaches was to think of MS as a disease of the nervous system that causes inflammation responsible for the neurodegenerative damage. The other approach was to think of MS as a disease that progresses from being an inflammatory condition into a neurodegenerative one.
The new study - conducted by researchers from the Medical University of Vienna in Austria and published in The Lancet Neurology - suggests that the inflammatory process drives the disease from onset to the later stages, with the neurodegenerative process occurring in the progressive phase of MS."
Article at:
http://www.medicalnewstoday.com/articles/289175.php
Fraudulent clinical trials known to FDA 'hidden from journals and public' in Medical News Today, 10 February 2015
Excerpts:
"Prof. Seife's investigation uncovered the following serious violations among the 57 clinical trials - yet only 3 of the 78 published reports for these research studies gave any mention of the misconduct identified by the FDA:
Fraudulent ("falsification or submission of false information") - 39% (22 trials)
Problems with the reporting of adverse events - 25% (14 trials)
Protocol violations - 74% (42 trials)
"Inadequate or inaccurate" recordkeeping - 61% (35 trials)
"Failure to protect the safety of patients" and/or issues with oversight or informed consent - 53% (30 trials)
Other violations not categorized - 35% (20 trials).
Prof. Seife gives the following conclusion: "When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct."
In addition to this failure of the people reporting their clinical trial results to reveal serious violations, there is no public disclosure by the FDA either, he notes:
"The FDA does not typically notify journals when a site participating in a published clinical trial receives an OAI inspection, nor does it generally make any announcement intended to alert the public about the research misconduct that it finds."
Article at:
http://www.medicalnewstoday.com/articles/289167.php
Worth watching: Why Prevention is Worth a Ton of Cure, NutritionFacts.org (5 minute video), January 2015
Anatabine Citrate/Anatabloc/Johnnie Williams---For those new to RCPI, or those that want to review the history of how it all came about.(as of a year ago) Article in the 'Inside Business, The Hampton Road Business Journal', August 2013 has a pretty objective article on how Johnnie Williams started out with productizing Anatabine Citrate and the history of it's development. The only parts I would give some caution to are the comments made by Adam Fuerstein. You need to go back to his diatrides and reviews vs his reviewers to see whether or not Fuerstein was objective or not. Having said that, the following excerpts point out that comments made about Parkinsons, thyroditis, etc had some notation in the evolution of Anatabloc:
"He became fascinated with an alkaloid substance called anatabine commonly found in tobacco and also in other plants such as tomatoes and eggplant. He became intrigued after reading various research reports suggesting anatabine could help cure a variety of diseases including Alzheimer's, schizophrenia, Parkinson's disease and multiple sclerosis, among others.
He followed closely the work of Dr. Paul Ladenson, a highly regarded endocrinologist at Johns Hopkins University School of Medicine. In 2004, Ladenson studied flight attendants who had chronic exposure to cigarette smoke while working aboard long-haul airplanes. They seemed to have lower instances of a destructive autoimmune thyroiditis called Hashimoto's disease that tends to strike women more than men. Another report by the Harvard School of Public Health showed smokers were 73 percent less likely to suffer from Parkinson's disease. Studies in England, Colorado and at Minnesota's Mayo Clinic suggested smoking may ease ulcerative colitis.
The point wasn't that smoking is beneficial; rather that something in tobacco smoke may have health benefits. Williams believed that agent was anatabine, and he started shedding his other tobacco-related research and products to focus on it. In 2007, he founded Rock Creek Pharmaceuticals as part of Star. In June 2012, the U.S. Patent and Trademark Office issued a patent to Rock Creek. It now operates large-scale commercial production of anatabine."
Article at:
http://insidebiz.com/news/profile-man-behind-gifts-jonnie-r-williams-sr
Interleukin 10---Wikipedia
Sounds like what Anatabine Citrate does
Excerpts:
"Interleukin-10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, IL-10 is encoded by the IL10 gene.[1] IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor 2 proteins.[2] Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively.[2]"
"Function:
IL-10 is a cytokine with multiple, pleiotropic, effects in immunoregulation and inflammation. It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-?B activity, and is involved in the regulation of the JAK-STAT signaling pathway.
Article at:
http://en.wikipedia.org/wiki/Interleukin_10
Phase I Clinical Studies To Begin Using Anatabine Citrate as Possible Therapy For MS in Multiple Sclerosis Today, posted in Cigx Discussion board by: 'Allan J. Kvasnicka' AJK
Article:
"Drug development company Rock Creek Pharmaceuticals, Inc. recently announced that a new clinical trial application with the United Kingdom’s Medicines Healthcare Products Regulatory Agency (MHRA) has been approved. The company is set to proceed with a Phase I study of its flagship pipeline product, Anatabine Citrate, a chemical that is found naturally in eggplant, potatoes, green tomatoes and other members of the Solanaceae family of plants, as well as in tobacco and tobacco smoke. The chemical is known for its anti-inflammatory properties unique from other anti-inflammatory drugs on the market, and may benefit patients with multiple sclerosis (MS).
The Phase I study will be composed of three portions, designed to evaluate Anatabine’s pharmacokinetic profile in the form of modified release formulation prototypes, and its safety and tolerability profiles in healthy volunteers. The first two parts will involve an open-label, non-controlled, single-dose study on 14 healthy participants, using six formula variations, with each administered dose spaced 7-14 days apart. The variations will be distinct in dose and duration of therapeutic action. This will allow the company to determine which formulation is most ideal, based on safety. The third and last part of the Phase I study will be a double-blind, placebo-controlled, seven-day multiple dose study of the identified optimal formulation in healthy subjects.
The Phase I clinical trial will base its success on two outcome measures, namely: “overall safety and tolerability through physical examination, vital signs, clinical chemistry, hematology, urinalysis and observation of adverse events (AE)” and “standard pharmacokinetics (PK) parameters and also pharmacodynamic (PD) assessment, specifically measuring the impact of the drug on inflammatory processes.”
“We are delighted to have been granted regulatory approval to begin our Phase I studies in the UK. This is the first clinical phase for our lead drug and will focus on safety and tolerability of six different formulations, 5 of which have modified release profiles and are of different doses. We look forward to generating our first human clinical data under this CTA,” said Dr. Michael Mullan, CEO of Rock Creek Pharmaceuticals.
Rock Creek’s UK-based partner, Quotient Clinical, is set to begin enrollment of healthy subjects this February 2015. While the company expects the study to stretch well into August, they expect to have a significant amount of research findings by mid-2015. Rock Creek also announced Quotient Clinical will be utilizing its RapidFACT® (Rapid Formulation development And Clinical Testing) service to hasten the development of these novel, oral, modified release formulations that have been co-developed between the two companies."
Article at:
http://multiplesclerosisnewstoday.com/2015/02/03/anatabine-citrate-by-rock-creek-pharma-to-start-phase-i-clinical-studies/
What’s Next, Part 2: The Singularity as Life Extension in Patrick Cox's Tech Digest, Patrick Cox, January 30, 2015, as posted on CIGX_VIPGROUP by: Allan J. Kvasnicka
Article:
What’s Next, Part 2: The Singularity as Life Extension
As I mentioned last week, I’m multitasking while I finish a book on tech advances and their investing implications. Last Friday, you saw an excerpt of my book manuscript called “What’s Next, Part 1: The Rise of Biocomputing.” This week, we look deeper into the so-called tech singularity and investigate life-extension therapies.
__________________________________________________________________
Last week, I explained again why I don’t think that the true singularity is some variation of the “Skynet malevolent artificial intelligence” story. Rather, I defer to John von Neumann, who coined the term to describe accelerating technological progress beyond which the consequences are beyond our capacity to predict. This, I believe, is true, but I think it’s generally a good thing.
As I said, modern economics has failed to adequately address or measure standard-of-living issues. We know implicitly that life has transformed in this generation simply by looking at the things that modern people, even those designated as “poor,” enjoy. In America, you can be officially living under the poverty line while owning a smartphone, a used car safer and faster than those owned by the richest people only a generation ago, a widescreen television, a microwave, and high-speed Internet access capable of delivering the whole of human art and knowledge.
Most important, we’re living much longer than ever before. A generation ago, the poor were hungry. Today, they’re more likely to be obese than the general population, which struggles not to consume the calories that have been in dangerously short supply throughout nearly all of human history. It’s hard to measure, but we have already entered into an age of abundance.
Personally, I think the most important abundance that has come about due to accelerating technological progress is time. We get to live far longer on average. Without life, who cares about yachts, jewels, overpriced wine or whatever else it is that only the rich are supposed to have?
Already, increased lifespans have caught Western nations unprepared for the rapidly growing population of older people. Historically high debt levels are fueled mostly by the cost of providing government services to an exploding older population. That’s the downside of a very high-class problem.
Health spans will continue to increase in an exponential manner. This, I believe, is the true singularity.
Moreover, I think it’s already happened. We don’t have to wait for transformational healthcare breakthroughs to be discovered. They already exist, though we’re waiting for them to be recognized, implemented, and in some cases approved by government. Some of these breakthroughs are so obvious we don’t notice them.
Vitamin D is perhaps the best example. Modern biotech tools have led to a complete rethinking of this steroidal regulator of nutrients. The community that spent much of its life warning about exposure to the sun, however, seems reticent to admit that they have inadvertently killed millions of people by recommending 25-hydroxyvitamin D blood levels that are clearly deficient.
There has, in fact, been a bloody fight between the old consensus and researchers on the cutting edge. Fortunately, the new consensus seems to be winning. Increasingly, we see studies covered in the popular media about the benefits of D levels much higher than those currently recommended by federal authorities in regard to cancer, cardiovascular disease, Alzheimer’s, and even childbirth. If you haven’t caught up with the research yet, I think the best place to start is UC San Diego’s GrassRootsHealth. If you have high melanin levels in your skin, you should be particularly concerned, because darker skin slows synthesis of vitamin D from sunshine, which is the major source for too many people.
The most interesting recent development on the vitamin D research front, by the way, comes out of Children’s Hospital Oakland Research Institute. Researchers working with the estimable Bruce N. Ames believe vitamin D regulates the enzyme that converts tryptophan into serotonin, a neurotransmitter believed to help regulate moods and facilitate long-term thinking. When serotonin is blocked, we see people acting on impulse without consideration of the long-term impacts of their actions.
Alarmingly, the researchers at Children’s Hospital Oakland Research Institute believe that low levels of vitamin D during pregnancy may permanently impact the ability of developing children to think in future terms. More research is need to verify this, but there’s already sufficient reason to encourage pregnant mothers to maintain adequate levels of vitamin D, along with folic acid and iron supplements. As stated before, women with high melanin counts are at particular risk of vitamin D deficiency. If you haven’t heard about this, it’s not because scientists aren’t interested. Too often, scientists are denied basic free-speech rights, as this article emphasizes.
So what will it mean for society to have most people’s vitamin D blood levels raised to optimal levels?
Obviously, we would see reductions in major diseases as well as their costs, but I think the best way to think about this is in terms of lifespans.
We may never have the kind of data on vitamin D and lifespans that will convince those who are predisposed to disbelieve the new research. This is because it’s extremely difficult to do longevity studies on humans. First, our lifespans are too long. A study would have to run nearly the length of the average life to be meaningful. Most people wouldn’t participate in double-blind controlled studies lasting for decades. Moreover, it would have to control exposure to sun, which would be extremely difficult and inconvenient.
Nevertheless, I think sufficient evidence exists to predict that widespread supplementation of vitamin D would have an immediate and profound impact on health spans and healthcare costs. Based on my own conversations with some of the people leading this research, the answer seems to be that optimal vitamin D blood levels translate into about 10% longer lives than those who are seriously deficient. Because some people are already supplementing vitamin D to some degree, I suspect there would be an increase in average lifespans of about five years.
It’s difficult to comprehend what a demographic change of this magnitude would do to our healthcare and Social Security systems, which are already strained. Clearly, people would have to invest earlier or work later in their lives. Vitamin D, however, is just the tip of the iceberg.
A study published December 18, 2014, in PLOS Genetics has attracted significant media attention. Texas A&M University biochemist Michael Polymenis and associates tested the common over-the-counter painkiller ibuprofen on a number of lower-order animals, including roundworms and houseflies. The outcome, which explains articles such as this one, was an increase of 10-17% in lifespans using the nonsteroidal anti-inflammatory drug (NSAID).
I’m pretty sure that we’ll see an increase in ibuprofen sales as a result of these stories. Despite prior research showing that ibuprofen suppresses inflammation and lowers risk of Alzheimer’s, Parkinson’s, and other age-related neurodegenerative diseases, I’m not convinced that ibuprofen will have comparable effects on humans.
I am convinced, however, that anatabine citrate will have this sort of impact on human lifespans. I get questions from people on a regular basis about the alkaloid, so I discuss what I know.
Rock Creek Pharmaceuticals has filed a clinical trial application (CTA) in the UK, as this press release relates. In a recent presentation, which you can watch here after free registration, CEO Dr. Michael Mullen said that the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) had asked for some minor additional information, but he expects to begin Phase 1 safety trials in this quarter. Personally, by the way, I would move to the UK if that were the only way to get anatabine citrate, and I know a lot of other people who feel the same.
If you watch the linked presentation, you’ll notice that video doesn’t appear of the multiple sclerosis mice that recovered due to anatabine citrate because of the format of the webcast. I’ve seen this video, however. You’ll also have to manually change slides, but you should watch the presentation if you’ve never heard the entire anatabine citrate story. There aren’t many stories this big in modern medicine. I also recommend emphatically that you watch Dr. Fiona Crawford’s presentation at the New College of Florida about traumatic brain injury and the effects of anatabine citrate. Interestingly, this same data was presented at a neurological conference, provoking the FDA to demand that Anatabloc, the over-the-counter version of anatabine citrate, be taken off the market. She also explains why scientists are so interested in neutraceuticals. Keep in mind that Crawfo rd is one of the key scientists behind the discovery of the amyloid role in Alzheimer’s. She’s also published an incredible number of articles accepted by top journals.
I spoke (a few days ago) to someone whose life was changed by anatabine citrate, specifically through amelioration of arthritis. She contacted Rock Creek Pharmaceuticals, which told her how to contact the FDA, which responded with the paperwork needed for compassionate-use distribution. She will need to find an MD willing to recommend use of the drug candidate. I haven’t yet heard confirmation from the company that it will distribute anatabine citrate through this kind of program, but I think those who want access should contact Rock Creek Pharmaceuticals.
The thing about anatabine citrate is that it’s a simple compound found in many foods. Taking the product is simple, and the impact is systemic, like vitamin D. Together, I think they will improve health spans by more than a decade, possibly much more.
I also recommend that you follow the mounting academic evidence supporting the efficacy of the nicotinamide adenine dinucleotide plus (NAD+) precursors, as I’ve previously written here. The two with the most research are nicotinamide riboside (Niagen) and oxaloacetate (benaGene).
All of these compounds, including dietary vitamin D, have the potential to significantly reduce healthcare costs in ways that legislation cannot. As you know, healthcare costs rise for most people as they age, so an older population therefore has higher medical costs—at least given the current state of medical science. As the population ages, demand for advanced healthcare services necessarily increases.
The only long-term solution is better health care capable of extending health spans and lowering the rate and cost of major diseases that are currently driving national debts globally. The technologies to do so exist now, and more of them will come online in the next few years. Soon to follow is radical regenerative medicine, which has the potential to extend life even further by returning cells and organs to full youthful health.
Increasingly, it appears that the solution to our health and budget problems is being held up by a regulatory system that is so utterly antiquated, it has become the primary obstacle to the biotechnologies that could reduce medical costs. People complain incessantly about the cost of drugs, but few understand that the major component of new drug costs is not research and development. Usually, it’s the costs associated with FDA-mandated clinical trials. A Forbes estimate put the cost to the pharmaceutical industry at $4 billion for every approved drug. Others say it’s only about $1.5 billion, but the difference isn’t that significant.
There are people in the FDA, however, who know that things have to change. Past FDA Chairman Dr. Andrew von Eschenbach is one of many important voices calling for the elimination of Phase 2 and 3 clinical trials. This isn’t a new idea. I spent much of my earlier life working with academics, including Milton Friedman, who have shown through rigorous research that the result of dramatic simplification of the drug approval process would be much less suffering and death, rather than the catastrophe predicted by some. Japan, as you know, has already done away with Phase 2 and 3 trials for the field of stem-cell medicine.
Japan’s deregulatory impulse is not a blip. Japan is simply further into the demographic transformation than we are, losing a quarter-million in population every year. So the Japanese have faced facts. They understand that they can no longer allow bureaucracies to control the rate of scientific progress. The same will happen here.
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Patrick Cox
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Mauldin Economics
Article at:
http://www.mauldineconomics.com/tech/tech-digest/whats-next-part-2-the-singularity-as-life-extension
Telomere-lengthening procedure turns clock back years in human cells in Gizmag, By Helen Clark, January 28, 2015
Excerpts:
"Researchers at the Stanford University School of Medicine have developed a new procedure to increase the length of human telomeres. This increases the number of times cells are able to divide, essentially making the cells many years younger. This not only has useful applications for laboratory work, but may point the way to treating various age-related disorders – or even muscular dystrophy"
"Cells treated with Stanford’s procedure multiply in a similar way to much younger cells, compared with untreated cells of the same age. According to the researchers, skin cells with telomeres lengthened by the procedure were able to divide around 28 more times than untreated cells, while muscle cells divided about three more times. With this new procedure, which uses modified RNA, many more cells can be easily generated for study and drug development or disease modeling."
""Our technique is nonimmunogenic," said postdoctoral scholar John Ramunas. "Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent."
Researchers are now testing the technique on other types cells and may try to treat accelerated aging disorders or target types of muscle cells in cases of Duchenne muscular dystrophy, or even heart disease."
Article at:
http://www.gizmag.com/telomere-extension-aging/35816/?utm_source=Gizmag+Subscribers&utm_campaign=333139fe1c-UA-2235360-4&utm_medium=email&utm_term=0_65b67362bd-333139fe1c-76708937
Dementia 'linked' to common over-the-counter drugs in BBC News Health, Michelle Roberts, 27 January 2015
Excerpts
:
"A study has linked commonly used medicines, including over-the-counter treatments for conditions such as insomnia and hay-fever, to dementia.
All of the types of medication in question are drugs that have an "anticholinergic" effect.
Experts say people should not panic or stop taking their medicines.
In the US study in the journal JAMA Internal Medicine, higher doses and prolonged use were linked to higher dementia risk in elderly people.
The researchers only looked at older people and found the increased risk appeared when people took drugs every day for three years or more"
"Drugs in the study
The US study does not name specific brands, but does outline the types of treatments investigated, which include:
Tricyclic antidepressants for treating depression
Antihistamines used to treat hay-fever and allergies
Antimuscarinics for treating urinary incontinence
Most of the drugs were given on prescription, rather than bought at the pharmacy over-the-counter."
Article at:
http://www.bbc.com/news/health-30988643
Tracking new information on Rock Creek, Quotient, Anatabine Citrate, Anatabloc, Chronic Inflammation, etc, try 'Google Alert' to notify you in your email when anything new is published on the web. Much easier than using search, web crawlers, meta search tools.
https://www.google.com/alerts?
Quotient website at:
http://www.quotientbioresearch.com/
New study may provide fresh avenues of treatment for patients suffering from skin diseases in GizMag, By Anthony Wood, January 15, 2015
Article:
"A fresh study carried out by researchers from King's College London (KCL) has established a link between a certain form of bacteria present on the skin following a surface wound and a type of white blood cell receptor, that together tip the scale away from the normal healing process and instead encourage the formation of cancerous tumors. The results of the study have the potential to create innovative treatment options for patients suffering from skin diseases, such as those that result in chronic ulcers and severe blistering.
There is a long standing association between tissue damage in patients suffering from chronic skin inflammation and the occurrence of cancerous tumors, however the reasoning behind the phenomenon has never been truly understood. The research carried out by KCL has brought us one step closer by establishing a link between the receptor found on the surface of white blood cells, Toll-like receptor 5 (TLR5), and the bacteria flagellin.
Over the course of the study, mice exhibiting chronic skin inflammation were wounded on their side, resulting in tumors forming around the break in the skin, with heightened levels of the protein HMGB1 being observed.
Ordinarily, the protective characteristics of unbroken skin prevent the flagellin and the white blood cells from interacting. However, when there is a break in the skin, the bacteria come into direct contact with the body's protective white blood cells, and more specifically, the TLR5 receptors that coat the outer layer of the tiny protectors.
When the receptors detect the bacteria, they increase the amount of HMGB1 present around the wound, and it is the heightened concentration of this protein that the team believes is responsible for disrupting the body's ordinary healing process, instead prompting the growth of cancerous tumors.
While the team is as of yet unsure how their findings will translate to human tumor growth, members have drawn a comparison with patients suffering from the disease epidermolysis bullosa, an extremely painful and debilitating condition that manifests itself through fragile skin and painful blisters.
Patients suffering from the disease run an increased risk of tumors forming around the open wounds that are so prevalent with this condition, and researchers have noted that, like the mice afflicted with chronic skin inflammation, sufferers of epidermolysis bullosa exhibit the same increased levels of HMGB1.
"These findings have broad implications for various types of cancers and in particular for the treatment of tumors that arise in patients suffering from chronic ulcers or skin blistering diseases," states lead author and Director of the Center for Stem Cells and Regenerative Medicine at KCL, Professor Fiona Watt. "Our findings raise the possibility that the use of specific antibiotics targeting bacteria in wound-induced malignancies might present an interesting clinical avenue."
The study is available in the online journal Nature Communications.
Source: King's College London"
Article at:
http://www.gizmag.com/kcl-skin-disease-cancer-tumor-flagellin-hmgb1-tlr5/35608/?utm_source=Gizmag+Subscribers&utm_campaign=858dec0a2a-UA-2235360-4&utm_medium=email&utm_term=0_65b67362bd-858dec0a2a-76708937
Study finds new treatment target for aggressive blood cancer in MNT, Catharine Paddock PhD, February 2015
Excerpt:
"Rsearchers have discovered an interaction between two molecules may contribute to the development of acute myeloid leukemia. They suggest the pathway could be a potential target for treating the aggressive blood cancer and that one of the molecules could serve as a biomarker in personalized therapy of the disease.
"PRL-3 and STAT3 form a regulatory loop that contributes to development of AML
The two molecules identified in the new study - which have been associated with AML before - are the transcription factor STAT3 and the gene PRL-3. A transcription factor is a protein that switches genes on and off by binding to DNA and other proteins.
The Singapore team was the first to report that PRL-3 is overexpressed in 47% of patients with AML. The authors note that higher cellular levels of STAT3 are also found in around 50% of cases of AML.
However, their new study is the first to show the two molecules form a regulatory loop that contributes to the development of AML.
Lead investigator Chng Wee Joo, associate professor at the NUS Yong Loo Lin School of Medicine and deputy director of CSI Singapore, says:
"Earlier studies on PRL-3 have been conducted in other cancers, but only in recent years has attention been turned to the significance of PRL-3 in blood cancer. Previously, the mechanism by which PRL-3 is regulated in AML has also not been fully elucidated."
For their study, the researchers created a core signature for STAT3 by analyzing large datasets in the literature. Using this core signature, they established that STAT3 was significantly enriched in AML patients with high PRL-3 expression.
Using mouse and human cells, they found that STAT3 binds to and promotes the production of PRL-3 in cells, and reducing levels of STAT3 lowered PRL-3 levels and diminished the malignancy of leukemic cells.
They conclude that disruption of this regulatory loop may be a promising way to treat AML and that PRL-3 could be a possible biomarker in personalized therapy for AML patients.
The team is now looking for ways to target the pathway in AML.
In April 2014, Medical News Today also learned about the idea that a gene within a gene drives acute myeloid leukemia. In a study published in Science Signaling, researchers from the US describe how they found it is a smaller gene embedded inside a larger gene already linked to poor survival of AML patients that actually drives progression of the disease."
Article at:
http://www.medicalnewstoday.com/articles/287902.php
My comments: Need help, look at this. Maybe Mullan/Paris/Crawford could help.
Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation.in PubMed, Paris D1, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C, Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M., November 2012
Abstract:
"Previous investigations have demonstrated the anti-inflammatory effects of cholinergic agonists, such as nicotine. In the present study, we investigated the potential anti-inflammatory activity of anatabine, a minor tobacco alkaloid also present in plants of the Solanacea family which displays a chemical structural similarity with nicotine. Our data show that anatabine prevents STAT3 and NF?B phosphorylation induced by lipopolysaccharide (LPS) or TNF-a in SH-SY5Y, HEK293, human microglia and human blood mononuclear cells. Using human whole blood, we found that anatabine prevents IL-1ß production induced by LPS. We assessed anatabine's anti-inflammatory activity in vivo using an acute model of inflammation by challenging wild-type mice with LPS. We observed that anatabine reduces pro-inflammatory cytokine production (IL-6, IL-1ß and TNF-a) in the plasma, kidney and spleen of the animals following the injection of LPS and concomitantly opposes STAT3 phosphorylation induced by LPS in the spleen and kidney. We also investigated the impact of anatabine on neuroinflammation using a transgenic mouse model of Alzheimer's disease (Tg APPsw) that displays elevated cytokine levels in the brain. Following a chronic oral treatment with anatabine, a reduction in brain TNF-a and IL-6 levels compared to untreated Tg APPsw mice was observed. Moreover, an increased STAT3 phosphorylation was detected in the brains of Tg APPsw mice compared to wild-type littermates and was inhibited by anatabine treatment. Overall our data show that the anti-inflammatory activity of anatabine in vitro and in vivo is mediated in part via an inhibition of STAT3 phosphorylation."
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/23178521
AbbVie wins U.S. approval for Parkinson's treatment in Reuters, Jan 12, 2015, no author cited
Article:
"(Reuters) - The U.S. Food and Drug Administration approved AbbVie Inc's treatment for Parkinson's disease.
The treatment, Duopa — a combination of carbidopa and levodopa — is the first to be effective for 16 hours, compared with existing oral formulations that last for up to four hours following a single dose.
Duopa, already available in Canada, is administered using a small portable infusion pump that delivers the drug directly to the small intestine.
AbbVie shares were up 1 percent in premarket trading.
Parkinson's disease is characterized by reduced levels of the hormone dopamine in the brain, which leads to poor mobility, slowness and stiffness.
Nearly all patients diagnosed with the disease are treated with levodopa. The effectiveness of oral levodopa, however, is limited by its short half-life. Excessive oral doses often lead to involuntary movements, or dyskinesia.
Last week, the FDA approved Impax Laboratories Inc's Parkinson's drug, Rytary, after rejecting it twice.
Other companies developing drugs for the disease include NeuroDerm Ltd, Acorda Therapeutics Inc and Cynapsus Therapeutics.
About 1 million Americans live with Parkinson's disease — more than the number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig's disease combined, according to the Parkinson's Disease Foundation."
Article at:
http://www.reuters.com/article/2015/01/12/us-abbvie-fda-idUSKBN0KL19120150112?feedType=RSS&feedName=healthNews
J&J strikes Alzheimer's research deal with Swiss firm AC Immune in Reuters, BEN HIRSCHLER AND CAROLINE COPLEY,Jan 12, 2015
Article:
"(Reuters) - Johnson & Johnson boosted its research efforts into battling Alzheimer's on Monday, striking a deal potentially worth more than $500 million to develop anti-tau vaccines with Swiss biotech firm AC Immune.
Tau is a protein known for forming twisted fibers inside brain cells and is linked to cell death. It is one of two abnormal proteins tied to the memory-robbing disease. The other is beta amyloid.
The hope is that therapeutic vaccines targeting tau will offer a way to treat Alzheimer's patients early in the disease.
It is a decade since the last drug was approved for Alzheimer's, and there is still no treatment that can slow its progression, with current drugs only easing some of its symptoms.
Unlisted AC Immune said on Monday it would receive an upfront sum and further payments based on scientific and commercial progress under the worldwide exclusive license agreement and research collaboration with J&J's Janssen Pharmaceuticals unit.
J&J will further develop AC Immune's lead therapeutic vaccine, ACI-35, which is currently in an early-stage Phase Ib clinical trial. ACI-35 is designed to stimulate the patient's immune system to produce a response against tau protein.
The deal is the fourth licensing agreement for AC Immune, which has another major tie-up with Roche for a beta amyloid-fighting drug called crenezumab.
Roche is due to make a decision about whether to advance crenezumab into late-stage testing, which will be crucial factor in determining how AC Immune's future pans out.
"We will leave our options open and see what the best steps for the company are. An IPO is one of the options," AC Immune's Chief Executive Andrea Pfeifer told Reuters in an interview.
AC Immune has a further vaccine, ACI-24, for preventing and clearing amyloid plaques in Phase I/IIa clinical trials.
Pfeifer said the company plans to start testing that vaccine in people with Down syndrome in the course of this year. Up to 75 percent of adults with the condition develop dementia."
Article at:
http://www.reuters.com/article/2015/01/12/us-ac-immune-j-j-idUSKBN0KL0GB20150112?feedType=RSS&feedName=healthNews
How To Age Well----- in Medcan Clinic, Dr. James Aw, no date
Excerpt:
"So what was it about the centenarians’ immune systems that allowed them to regulate their immune systems so well for so long? The answer may lie in a study published in 2011 by a researcher from the Mayo Clinic, Dr. James Kirkland. It could have something to do with the accumulation of senescent cells — so called “deadbeat” cells that stop functioning but nevertheless continue to live. The Kirkland study established that removing senescent cells in mice can extend mouse lifespans — opening the door to future treatments that extend lifespans in humans by decreasing immune-cell senescence.
Today, clinical medicine is beginning to harness and control the chronic inflammatory process. By testing levels in the blood of a substance called hsCRP, we can now assess whether a given patient is experiencing acute inflammation — and the future is likely to bring us more sophisticated testing of chronic inflammation with such biomarkers as interleukin, insulin growth factor and tumour necrosis factor.
Meanwhile, a new class of drugs, known as biologics, are targeting some diseases that arise from chronic inflammatory states, such as inflammatory bowel diseases, rheumatoid arthritis and autoimmune disorders.
Could new types of biologic drugs help us control the inflammatory response associated with aging itself? Could environmental interventions, such as a customized diet, help regulate the chronic inflammatory response? And would that, in turn, help more people to live well to the age of 100? As I left Dr. Khoury’s presentation in New Orleans, I felt excited about the prospects."
Article at:
http://www.medcan.com/articles/age_well/
Centenarians as a model for healthy aging in Research Gate, Claudio Franceschi, University of Bologna,
Excerpt:
"inflammaging is considered the common and most important driving force of age-related pathologies, such as neurodegeneration, atherosderosis, diabetes, sarcopenia, among others."
Abstract at:
http://www.researchgate.net/publication/10840692_Centenarians_as_a_model_for_healthy_aging
Positive biology”: the centenarian lesson in Immunity and Aging, 2012, Calogero Caruso1*, Giuseppe Passarino2, Annibale Puca3 and Giovanni Scapagnini4
* Corresponding author: Calogero Caruso calogero.caruso@unipa.it
Excerpt:
"Abstract
The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies.
Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected people in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. To discuss the relevance of genetics and life style in the attainment of longevity, five papers mostly focused on Italian centenarians have been assembled in this series. The aim is to realize, through a” positive biology” approach (rather than making diseases the central focus of research, “positive biology” seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being) how to prevent and/or reduce elderly frailty and disability.
Keywords: Ageing; Frailty; Longevity; “Positive Biology”
Introduction
During the last century, life expectancy at birth rose by a remarkable 30?years in Western countries and in Japan, initially because of reductions in infant, child, and maternal mortality and then because of declining mortality in middle and old age. So, during the past century, humans have gained more years of average life expectancy than in the last 10,000?years: we are now living in a rapidly ageing world. The sharp rise in life expectancy, coupled to a steady decline in birth rates in all developed countries, has led to an unprecedented demographic revolution characterized by an explosive growth in the number and proportion of older people. In 1900, about 40% of babies born in Western countries were expected to live beyond age 65. Today in these same countries more than 88% of all newborns will live past age 65 and at least 44% will live beyond age 85. The number of people aged 60?years or older exceeded 635 million in 2002, and is expected to grow to nearly 2 billion by 2050. The proportion of people aged 60 and over stands about 1 in 4 in many Western countries as well as in Japan. Should the present trend continues, this ratio is expected to reach 1 in 3 by 2050. So, many countries have rising ageing populations and are facing an increased prevalence of age-related diseases and increasing healthcare costs, since the rapid rise in older people is accompanied by an increase in the number of people with chronic age-related diseases. However, the improvement in public health has reduced the principal causes of mortality in the elderly, allowing an increasing number of individuals to reach the maximum lifespan age. Indeed, around the 1950s, in all industrialized countries, the progressive decline of mortality in oldest old people has increased, so that the number of centenarians has augmented about 20 times [1-6]. Nowadays it is reasonable to assume that the total number of centenarians is more than three hundred thousand people worldwide [7].
The increased ability to reach 100?years in industrialized countries over the last 150?years most likely reflects a rise in life expectancy as a consequence of improvements in diet and a reduced exposure to infection and inflammation [1]. In favour of diet as a modulator of longevity, the Elderly Prospective Cohort Study identified a reduced overall mortality among the elderly consuming a modified Mediterranean diet in which saturated fatty acids were substituted for monounsaturated ones [8] and the zones of Sardinia and Sicily characterized by male longevity are characterized by close adherence to Mediterranean diet [9]. The traditional Mediterranean diet provides about 40% of calories from fat, mostly monounsaturated and polyunsaturated fat [8]. Concerning Japanese centenarians, traditional Okinawan diets provide about 90% of calories from vegetables carbohydrate, therefore it is low in calories but nutritionally dense, particularly with regard to vitamins, minerals, and phytonutrients [10]. Concerning inflammation, the reduction in lifetime exposure to infectious diseases and other sources of inflammation, the cohort mechanism, has been suggested to contribute to the historical decline in old-age mortality, suggesting long-life pathogen burden as the most important factor for age-related inflammation. Accordingly, some studies have linked an individual exposure to past infection to levels of chronic inflammation and to increased risk of heart attack, stroke, and cancer [11-14].
The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years for the increase of the subjects which are not autonomous and are affected by invalidating pathologies [15].
Recently, it has been pointed out that most biomedical research should be termed ‘negative biology’, because the study of disease is its central heart, reflecting the prevalence of pathology-oriented negative biology, so focusing on the causes of pathology. By contrast, the Author invites to focus on a different approach, named “positive biology”. Rather than making diseases the central focus of research, positive biology seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being [16]. In particular, concerning our topic, this means to understand why some individuals, i.e. the centenarians, have escaped neonatal mortality, pre-antibiotic era diseases, and fatal outcomes of age-related diseases, so leaving more than 100?years [17,18]. Investigating the biological mechanisms underlying centenarian longevity, therefore, shows an interesting conundrum for positive biology. The knowledge grew out of this approach could allow to modulate the rate of ageing providing valuable information on the lifestyle to achieve healthy ageing. In addition, studying centenarians might supply important indications how to build up drugs that can slow or delay ageing, with benefits for those who are more vulnerable to disease and disability [19,20].
The model of centenarians is not simply an additional model with respect to well-studied organisms, since the study of humans has revealed characteristics of ageing and longevity as geographical and sex differences, role of antigenic load and inflammation, which did not emerge from studies in laboratory model systems and organisms. So, scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of successful ageing [17,18].
Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected peope in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped [17,18].
The ageing process and longevity are multi-factorial events. Genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. As well known, life expectancy is a familial trait and longevity is determined by different factors. Epidemiological evidence for a genetic component to variation in human lifespan comes from twin studies and family studies. By comparing life span in twins, researchers have found that approximately 25% of the overall variation in human lifespan can be attributed to genetic factors, which become more relevant for extreme longevity [21-24]. Conditioning factors, that arise in the first part of life (socio-economic state of parents, education and month of birth, which has been found to reflect the environmental conditions during the prenatal and early postnatal period), account for another 25% of such variability; life circumstances at adult and old age (including socio-economic status and medical assistance) may account for about the remaining 50% [25]. In this context, the study of centenarian offspring, a group of healthy elderly people with a familiar history of longevity, might help gerontologists to better identify the correlation between genetic profile and hope of a healthy ageing. Previous studies have reported that centenarian offspring, like their centenarian parents, have genetic and immune system advantages, which reflect a minor risk to develop major age-related diseases, such as cardiovascular diseases, hypertension or diabetes mellitus as well as cancer [26,27]."
Article at:
http://www.immunityageing.com/content/9/1/5
M&A Boom Seen in 2014 as Drug Hunt Spurs Biotech Deals in Bloomberg,
Meg Tirrell and David Welch Jan 10, 2014
Article:
"Health-care companies with deep pockets and shallow product pipelines are poised for a busy year of acquisitions, with biotechnology firms likely to be among the most prominent targets even as they trade at record highs.
The seeds of this year’s deals may be planted next week at JPMorgan Chase & Co. (JPM)’s annual health-care conference in San Francisco, where more than 300 companies will present to thousands of investors about the year ahead. Meanwhile, business development executives will be meeting in hotels surrounding the conference that begins Jan. 13.
Large drugmakers from Merck & Co. (MRK) to Bristol-Myers Squibb Co. (BMY) are dealing with patent expirations on top medicines and cutting researchers as they refocus their product development strategies. At the same time, prices on targets are expected to stabilize after last year’s run-up, said Jeff Stute, JPMorgan’s head of health-care investment banking.
“We see M&A in the health-care sector being up materially in 2014 at all size levels and across all subsectors,” Stute said in a telephone interview. “Buyers and sellers will get comfortable with the new reality of where assets are priced.”
Biotechnology companies in particular had a standout 2013, with the Nasdaq Biotechnology Index gaining 66 percent, topping a 30 percent increase for the Standard & Poor’s 500 (SPX), and closing yesterday at a record high of 2,449.25. The industry saw the most IPOs since 2000, as investors were drawn to the prospects of revenue growth in an industry seeing a record number of new drug approvals over two years.
Generic Competition
That’s against a backdrop of patent expirations at some of the industry’s biggest companies. More than $60 billion in revenue was lost by the pharmaceutical industry to cheaper generic competition from 2010 to 2012, according to research by analysts at Bloomberg Industries. Another $50 billion may be lost in the next five years.
In response, companies have cut jobs, reorganized units and, in some cases, sold them to save money. That’s boosted cash in hand for many, opening the way for acquisitions.
Deal activity has already taken off in 2014. This week, General Electric Co. (GE) agreed to pay about $1.06 billion for medical equipment businesses from Thermo Fisher Scientific Inc. (TMO), while Forest Laboratories Inc. (FRX) said it will buy Aptalis Pharma for $2.9 billion to add treatments for gastrointestinal ailments and cystic fibrosis. New York-based Forest’s stock rose 18 percent, the most in at least 33 years.
“Based on the strong stock price reaction to strategic M&A announcements, shareholders are telling companies they want them to do M&A,” Stute said. “Companies are feeling pressure to evaluate M&A opportunities more aggressively in part because their stocks have underperformed competitors who have engaged in material strategic acquisitions.”
Adding $85 Billion
Perhaps the most dramatic example is Gilead Sciences Inc. (GILD)’s purchase of hepatitis C drug maker Pharmasset Inc. for $11 billion. Since the deal was announced in November 2011, Gilead’s stock has almost tripled, adding almost $85 billion in market value and making the Foster City, California-based drugmaker the biggest biotechnology company in the world. The drug Gilead gained in the deal, Sovaldi, was approved by the U.S. Food and Drug Administration in December and is projected to generate $2.5 billion in revenue this year.
Sovaldi’s approval capped a year of 27 clearances at the FDA that included several under a new “breakthrough therapy” designation prioritizing reviews of promising medicines. That followed a record 2012 in which 39 novel drugs were approved, the most in 15 years.
FDA Shift
“The regulatory environment has shifted to being somewhat more accommodating than it was before,” Ron Cohen, chief executive officer of Acorda Therapeutics Inc. (ACOR), said in a telephone interview. “The feeling is the FDA is not being as much of a drag to progress, and in some cases they may actually be potentiating bringing innovation to market.”
Cohen cited the breakthrough therapy track as an example of the FDA’s willingness to speed important drugs through the approval process, part of a movement on the agency’s part to give patients and their physicians more of a say in weighing medicines’ risks and benefits.
Cancer drugs helped boost 2012 approvals to their record and were among those granted breakthrough designation last year, including Johnson & Johnson (JNJ) and Pharmacyclics Inc. (PCYC)’s Imbruvica and Roche Holding AG (ROG)’s Gazyva, both for blood cancer.
Medicines for oncology as well as for rare diseases are among the most coveted by acquirers, Stute said. The drug industry’s biggest companies are seeking ways to plug revenue holes left by patent expirations on some of their top products, including New York-based Pfizer Inc. (PFE)’s Lipitor and Merck’s Singulair.
Looking to Buy
Bristol-Myers, which had $6.3 billion in cash as of Sept. 30, has said it will be aggressive in dealmaking, looking for purchases in cancer, virology and specialty drugs. Merck, the second-largest U.S. drugmaker, also has said it plans to invest heavily in M&A. With $18.2 billion in cash and equivalents as of Sept. 30, the company recently overhauled its research and development activities, cutting programs and saying it would look externally to fill its pipeline.
Other areas of health-care are also likely to see more deals, including diagnostics, Stute said.
“I actually don’t think there’s a subsector within health care that is likely to be quiet,” he said. “We expect M&A is going to be the theme that people are talking about more than anything this year” at the JPMorgan conference.
This year’s event is expected to be the biggest in its history, reflecting the record year left behind and optimism for the year ahead. Ken Moch, CEO of Chimerix Inc. (CMRX), a developer of antiviral drugs, said he expects attendees to be “cautiously giddy.”
“I’ve been going a long time and I’ve been through moods where everybody wants to kill themselves and everybody is giddy,” Moch said. “Everybody wants to see how this year starts off.”"
Article at:
http://www.bloomberg.com/news/2014-01-10/m-a-boom-seen-in-2014-as-drug-hunt-spurs-biotech-deals.html
Shire to buy NPS for $5.2 billion to boost rare disease drugs in Reuters, BY BEN HIRSCHLER, LONDON Sun Jan 11, 2015
Article:
"
(Reuters) - Shire Plc has agreed to buy NPS Pharmaceuticals Inc for $5.2 billion in its biggest acquisition yet, as the Dublin-based drugmaker strengthens its position in the lucrative field of medicines for rare diseases.
The takeover continues the breakneck pace of deal-making in 2014 in the pharmaceuticals sector, as companies jockey for promising assets amid a wave of new drugs emerging from research laboratories.
Shire Chief Executive Officer Flemming Ornskov told Reuters he would keep looking for more deals to grow the company into a biotech powerhouse.
Shire will pay $46.00 per NPS share, representing a premium of nearly 10 percent to NPS' Friday close, the two companies said on Sunday.
The move will not come as a huge surprise, since Shire was first linked to NPS in May 2014. When plans for Shire to sell itself to AbbVie Inc fell apart in October, Shire said it could look again at earlier deal prospects and reports of Shire's interest resurfaced in mid-December.
"This is about growth and rare diseases, and it fits hand in glove with our strategy and our franchise," Ornskov said.
Shire expects the all-cash deal to add to its adjusted earnings from 2016 onward. It believes it can achieve cost savings of approximately 25 percent to 35 percent of consensus forecasts for NPS' standalone future operating cost base from 2017.
The acquisition of New Jersey-based NPS will give Shire two significant new drugs. Gattex, a treatment for short-bowel syndrome, is already on the market, while Natpara, for hypoparathyroidism, is awaiting approval from the U.S. Food and Drug Administration.
The FDA is slated to decide on the Natpara application by Jan. 24. "I am confident that Natpara will be approved on the 24th, however ... there is absolutely no guarantee," said NPS CEO Francois Nader. "Given our interactions with the FDA, I believe it will be approved."
Nader called Shire's decision to conclude a deal before a decision "a calculated risk on their part," that nevertheless "would provide the joint company the opportunity to deploy the most resources in supporting the launch."
Consensus analyst forecasts for the two NPS medicines point to annual sales of $509 million and $534 million respectively by 2019, according to Thomson Reuters Cortellis, although Ornskov believes they may bring in more.
"Both of them have significant sales potential and some have mentioned the word 'blockbuster'," he said. The term blockbuster applies to a drug with sales of $1 billion or more.
"ALWAYS CONSIDERING NEXT DEAL"
Shire, which will tender NPS shares, has secured an $850 million bank loan which, together with cash reserves and an existing $2.1 billion five-year revolving credit facility, will pay for the deal.
Even though NPS is a record acquisition for Shire, Ornskov expects the deal, which could close in the first quarter of this year, to be paid off quickly.
"We are incredibly cash-generative and this will add to that, so this does not prevent us from considering further deals," he said. "Shire is always considering the next deal."
Shire's coffers were boosted to the tune of more than $1.6 billion when it got a windfall break-up fee after AbbVie walked away from its $55 billion takeover bid.
Citigroup and Lazard acted as joint financial advisers to Shire, with Goldman Sachs and Leerink advising NPS.
(Additional reporting by Natalie Grover and Deena Beasley; Editing by Ruth Pitchford and Jeffrey Benkoe)
Article at:
http://www.reuters.com/article/2015/01/11/us-nps-m-a-shire-idUSKBN0KK0QE20150111
Antibiotics: US discovery labelled 'game-changer' for medicine in BBC News Health, James Gallagher, Health editor, BBC News website, 7 January 2015
My comments: Another 'natural' derived solution, wonder if it is patentable?
Article:
"he decades-long drought in antibiotic discovery could be over after a breakthrough by US scientists.
Their novel method for growing bacteria has yielded 25 new antibiotics, with one deemed "very promising".
The last new class of antibiotics to make it to clinic was discovered nearly three decades ago.
The study, in the journal Nature, has been described as a "game-changer" and experts believe the antibiotic haul is just the "tip of the iceberg".
The heyday of antibiotic discovery was in the 1950s and 1960s, but nothing found since 1987 has made it into doctor's hands.
Since then microbes have become incredibly resistant. Extensively drug-resistant tuberculosis ignores nearly everything medicine can throw at it.
Back to soil
The researchers, at the Northeastern University in Boston, Massachusetts, turned to the source of nearly all antibiotics - soil.
This is teeming with microbes, but only 1% can be grown in the laboratory.
The team created a "subterranean hotel" for bacteria. One bacterium was placed in each "room" and the whole device was buried in soil.
It allowed the unique chemistry of soil to permeate the room, but kept the bacteria in place for study.
Graphic showing how bacteria are grown
The scientists involved believe they can grow nearly half of all soil bacteria.
Chemicals produced by the microbes, dug up from one researchers back yard, were then tested for antimicrobial properties.
The lead scientist, Prof Kim Lewis, said: "So far 25 new antibiotics have been discovered using this method and teixobactin is the latest and most promising one.
"[The study shows] uncultured bacteria do harbour novel chemistry that we have not seen before. That is a promising source of new antimicrobials and will hopefully help revive the field of antibiotic discovery."
Bacteria
Tests on teixobactin showed it was toxic to bacteria, but not mammalian tissues, and could clear a deadly dose of MRSA in tests on mice.
Human tests are now needed.
The researchers also believe that bacteria are unlikely to develop resistance to teixobactin.
It targets fats which are essential for building the bacterial cell wall, and the scientists argue it would be difficult to evolve resistance.
"Here is an antibiotic that essentially evolved to be free of resistance," said Prof Lewis. "We haven't seen that before.
"It has several independent different tricks that minimise resistance development."
line
Bacteria
Analysis
By James Gallagher, health editor, BBC News website
There are limits to the discovery of the antibiotic teixobactin, which has yet to be tested in people.
It works on only Gram-positive bacteria; this includes MRSA and mycobacterium tuberculosis.
It cannot penetrate the extra layer of protection in Gram-negative bacteria such as E. coli.
But even if their method does mark a new era of antibiotic discovery there are big questions.
Sir Alexander Fleming, who discovered penicillin, warned of the dangers of resistance back in his Nobel prize speech in 1945.
Yet even now prescriptions in England are rising, with half deemed "inappropriate" and contributing to the problem.
But can we be trusted with new antibiotics? Or will we make the same mistakes again?"
Article at:
http://www.bbc.com/news/health-30657486
Right on Target
Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation in PubMed, Paris D1, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C, Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M.
January 5, 2013
Abstract:
"Previous investigations have demonstrated the anti-inflammatory effects of cholinergic agonists, such as nicotine. In the present study, we investigated the potential anti-inflammatory activity of anatabine, a minor tobacco alkaloid also present in plants of the Solanacea family which displays a chemical structural similarity with nicotine. Our data show that anatabine prevents STAT3 and NF?B phosphorylation induced by lipopolysaccharide (LPS) or TNF-a in SH-SY5Y, HEK293, human microglia and human blood mononuclear cells. Using human whole blood, we found that anatabine prevents IL-1ß production induced by LPS. We assessed anatabine's anti-inflammatory activity in vivo using an acute model of inflammation by challenging wild-type mice with LPS. We observed that anatabine reduces pro-inflammatory cytokine production (IL-6, IL-1ß and TNF-a) in the plasma, kidney and spleen of the animals following the injection of LPS and concomitantly opposes STAT3 phosphorylation induced by LPS in the spleen and kidney. We also investigated the impact of anatabine on neuroinflammation using a transgenic mouse model of Alzheimer's disease (Tg APPsw) that displays elevated cytokine levels in the brain. Following a chronic oral treatment with anatabine, a reduction in brain TNF-a and IL-6 levels compared to untreated Tg APPsw mice was observed. Moreover, an increased STAT3 phosphorylation was detected in the brains of Tg APPsw mice compared to wild-type littermates and was inhibited by anatabine treatment. Overall our data show that the anti-inflammatory activity of anatabine in vitro and in vivo is mediated in part via an inhibition of STAT3 phosphorylation."
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/23178521
The Restrained Expression of NF-kB in Renal Tissue Ameliorates Folic Acid Induced Acute Kidney Injury in Mice in PLOS/ONE, Dev Kumar,
Surinder K. Singla, Veena Puri, Sanjeev Puri mail
Published: January 05, 2015
Abstract:
"The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.
Paper at:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0115947
NF-kappaB and MAP Kinase Signaling in Inflammation (X4)
joint with the meeting on Ubiquitin Signaling (X3)
Keystone Symposia on Molecular and Cellular Biology
Scientific Organizers: Steven C. Ley, Zhijian 'James' Chen and Jenny P.Y. Ting
March 13—17, 2016
Whistler Conference Centre, Whistler, British Columbia, Canada
DEADLINES:
Scholarship Deadline: Nov 11, 2015 [details]
Discounted Abstract Deadline: Nov 11, 2015 [details]
Abstract Deadline: Dec 14, 2015 [details]
Discounted Registration Deadline: Jan 13, 2016 [details]
My comments: Interesting conference focused on NF-kappaB and inflammation scheduled over a year away---wonder if RCPI will participate?
Announcement at:
http://www.keystonesymposia.org/16X4
Very Early Administration of Progesterone for Acute Traumatic Brain Injury, David W. Wright, M.D., Sharon D. Yeatts, Ph.D., Robert Silbergleit, M.D., Yuko Y. Palesch, Ph.D., Vicki S. Hertzberg, Ph.D., Michael Frankel, M.D., Felicia C. Goldstein, Ph.D., Angela F. Caveney, Ph.D., Harriet Howlett-Smith, R.N., Erin M. Bengelink, M.A., Geoffrey T. Manley, M.D., Ph.D., Lisa H. Merck, M.D., M.P.H., L. Scott Janis, Ph.D., and William G. Barsan, M.D. for the NETT Investigators
N Engl J Med 2014; 371:2457-2466, December 25, 2014
Article:
"BACKGROUND
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI.
METHODS
We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score.
RESULTS
A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P=0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes.
CONCLUSIONS
This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. (Funded by the National Institute of Neurological Disorders and Stroke and others; PROTECT III ClinicalTrials.gov number, NCT00822900.)"
Article at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1404304?query=neurology-neurosurgery
John Mauldin/Patrick Cox vs FDA posted by smokey_joe in CIGX_VIPGROUP, article in The Flat Debt Society - Mauldin Economics, October 20, 204
Excerpt:
"Replace the FDA
But the worst flaw is in our drug regulatory process. Only a few months ago the FDA (Food and Drug Administration) was doing everything it could to slow down the development of new drugs for Ebola. Now that there are a few cases of Ebola in the US and we have a general news panic, it seems they can’t encourage drug development fast enough. Nothing changed except the politics.
A few people in the US contract Ebola and suddenly the FDA allows companies to pull out all the stops. My side bet is that we will have a cure for Ebola in the not-too-distant future.
The serious tragedy here is that millions of people die every year from all sorts of diseases that are on the verge of being cured. There are very hopeful new technologies in the labs, but the FDA is preventing them from getting to you. When I say millions of people that is NOT an exaggeration. But those diseases haven’t caused a political firestorm. We need to change that. We need to create a firestorm to force change on the most deadly bureaucracy in America.
There are hundreds of life-saving drugs and other therapies that are being kept from you and me because bureaucrats are using 19th-century science to try to deal with technologies developed in the 21st century. They are more interested in protecting their personal fiefdoms and reputations than in saving lives. Gods forbid we have a drug that might cause a problem, so they sacrifice progress and our collective health – indeed our very lives – on the altar of self-interested bureaucratic expediency. Oh, they couch it in all sorts of high-sounding words, but the results are the same. You and I are prevented from making good choices about our own healthcare and saving the lives of our loved ones.
The FDA does not need to be reformed; it needs to be replaced. We need as a country to create a commission to design a 21st-century Drug Regulatory Authority and then turn over the regulatory process to this new authority. If any of the current structure fits in the new system, then fine. Otherwise, close it down.
As an economist, I would point out that we are leading the world in biotechnology research, but we’re going to see that research create jobs elsewhere if we don’t figure out how to develop the cures and procedures in this country. We need to slash the cost of drug development by 90%. If we do that, we will see the number of new drugs and procedures increase by orders of magnitude.
Pat Cox and I are watching companies that have the ability to cure scores of some of the most debilitating diseases known to mankind, but they are frustrated at every level by the FDA. And the technologies that are on the drawing board are even more mind-blowing. We simply have to get our heads around this situation and make the needed changes."
Article at:
http://www.mauldineconomics.com/frontlinethoughts/the-flat-debt-society#replace