Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Alzheimer's Disease Fast Facts
Posted: May 26, 2015 1:39 PM PDT
Updated: May 26, 2015 1:39 PM PDT
CNN Library
Excerpt:
(CNN) -- "Here is some information about Alzheimer's disease, a progressive brain disorder that damages and destroys brain cells, leading to loss of memory and other intellectual abilities."
TM & © 2015 Cable News Network, Inc., a Time Warner Company. All rights reserved.
Article at:
http://www.erietvnews.com/story/29159577/alzheimers-disease-fast-facts
Cellular Inflammation: The Secret Killer (Article) in 'Inflammation Research Foundation', Health: The Fires Within, Christine Gorman, Alice Park and Kristina Dell, 2015
Excerpts:
"Suddenly, inflammation has become one of the hottest areas of medical research. Hardly a week goes by without the publication of yet another study uncovering a new way that chronic inflammation does harm to the body. It destabilizes cholesterol deposits in the coronary arteries, leading to heart attacks and potentially even strokes. It chews up nerve cells in the brains of Alzheimer’s victims. It may even foster the proliferation of abnormal cells and facilitate their transformation into cancer. In other words, chronic inflammation may be the engine that drives many of the most feared illnesses of middle and old age.
This concept is so intriguing because it suggests a new and possibly much simpler way of warding off disease. Instead of different treatments for, say, heart disease, Alzheimer’s and colon cancer, there might be a single, inflammation-reducing remedy that would prevent all three.
Chronic inflammation also fascinates scientists because it indicates that our bodies may have, from an evolutionary perspective, become victims of their own success. “We evolved as a species because of our ability to fight off microbial invaders,” says Dr. Peter Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital in Boston. “The strategies our bodies used for survival were important in a time when we didn’t have processing plants to purify our water, when we didn’t have sewers to protect us.”
But now that we are living longer, those same inflammatory strategies are more likely to slip beyond our control. Making matters worse, it appears that many of the attributes of a Western lifestyle — such as a diet high in sugars and saturated fats, accompanied by little or no exercise — also make it easier for the body to become inflamed."
"This new view of inflammation is changing the way some scientists do medical research. “Virtually our entire R and D effort is [now] focused on inflammation and cancer,” says Dr. Robert Tepper, president of research and development at Millennium Pharmaceuticals in Cambridge, Mass. In medical schools across the U.S., cardiologists, rheumatologists, oncologists, allergists and neurologists are all suddenly talking to one another — and they’re discovering that they’re looking at the same thing. The speed with which researchers are jumping on the inflammation bandwagon is breathtaking. Just a few years ago, “nobody was interested in this stuff,” says Dr. Paul Ridker, a cardiologist at Brigham and Women’s Hospital who has done some of the groundbreaking work in the area. “Now the whole field of inflammation research is about to explode.”"
Article at:
http://www.inflammationresearchfoundation.org/inflammation-science/inflammation-details/time-cellular-inflammation-article/
BACE1 Article quote:
"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
A New Look at Brain Inflammation in Alzheimer's in 'Dana Foundation News', Jim Schnabel, January 16, 2013
Excerpts:
"The two best-known signs of Alzheimer’s, in the brains of its victims, are the plaques of amyloid beta protein and tangles of tau protein. But the disease also features chronic inflammation. Cells known as microglia—neural cousins of pathogen-eating macrophages of the bloodstream—swarm around amyloid plaques and dying, tangle-ridden neurons. They seem helpful, gobbling up amyloid beta as well as disease-damaged cells. But does their immunological enthusiasm also cause harm to healthy cells—could it accelerate the disease or even help to initiate it? Scientists have debated these questions for more than two decades, without any firm resolution. Now a burst of new research suggests that inflammation does, indeed, play a major role in Alzheimer’s—and that targeting specific elements of that inflammation could be useful in treating or preventing the disease" -
"Since the late 1980s, various studies have found hints that the chronic inflammation found in Alzheimer’s hastens the disease process, and may even be a disease trigger. A history of serious head injury, which typically causes brain inflammation, is known to be a risk factor for Alzheimer’s. Systemic infection—another cause of inflammation—also appears to accelerate the disease. Several epidemiological studies have found that older people who use anti-inflammatory drugs regularly appear to have significantly lower incidences of Alzheimer’s.
The value of those epidemiological studies came into question several years ago, when more rigorous placebo-controlled clinical trials of anti-inflammatory drugs—ibuprofen, naproxen, and celecoxib, for example—failed to show signs of helping people who already have Alzheimer’s dementia or early cognitive impairment. In some cases these drugs apparently accelerated the course of the disease. Yet in a little-publicized study, published in late 2011, naproxen seemed to have a marked effect in preventing the disease: It reduced the incidence of Alzheimer’s among elderly people who started out cognitively normal and took the drug for more than two years."
"How each of these inflammation pathways relates to the Alzheimer’s disease process is not yet clear. But in the MRP14 study, Heneka and his colleagues found that the protein doesn’t just push microglia into an activated, inflammatory state. It also somehow increases the presence and activity of a neuronal enzyme, BACE1, that helps to produce amyloid beta, and thus increases amyloid beta production. Heneka suspects that inflammation helps to start the disease process by boosting the production of amyloid beta—and then helps to sustain the process by reducing the ability of microglia to remove amyloid beta. A key point is that amyloid beta accumulation seems to be both a cause and an effect of chronic inflammation."
"Analyses of the brain changes in these mice, and comparisons to brain tissue from people with Alzheimer’s, suggest to her that inflammation may help trigger Alzheimer’s by exacerbating a common age-related problem with neurons. As they get older and their functions become less efficient, neurons lose their ability to transport and properly dispose of proteins. [See recent Dana briefing paper.] This decline is apt to show up first in neurons’ output stalks, or axons, which, being long and thin, are particularly vulnerable to a disruption of their internal transport systems. If enough proteinaceous waste builds up in an axon, it will swell—a feature often seen in Alzheimer’s brains—and may try to bubble off a waste-filled granule, which will then be consumed by nearby microglia.
Inflammation worsens this problem in several ways: First, it increases the production of amyloid-beta in inflamed regions. Second, it stresses neurons and hastens the age-related decline of their protein-transport and disposal systems. Third, it pushes microglia into a reactive, inflammatory state and thus reduces their ability to clear up axons’ expelled waste."
Article at:
http://dana.org/News/Details.aspx?id=43258
China's new Alzheimer's disease drug applies for clinical tests in 'Xinhua', 2015-05-24
Article:
"GUANGZHOU, May 24 (Xinhua) -- China will begin clinical tests on a new drug for Alzheimer's disease (AD), after animal tests showed positive results.
AD16, developed by Guangzhou Institute of Biomedicine and Health (GIBH) under the Chinese Academy of Sciences, has proven effective in improving the memory and cognitive abilities of guinea pigs, Hu Wenhui, head of the development team, told Xinhua on Sunday.
Hu said AD16 functions as an anti-neuroinflammatory agent and can alleviate damage caused by amyloid beta protein on neurons, thus, slowing the disease's progression.
Alzheimer's affects tens of millions of elderly people worldwide, yet there is no effective cure. The cause of the disease is poorly understood, although scientists have linked it to a build-up of the amyloid beta protein in brains."
Article at:
http://news.xinhuanet.com/english/2015-05/24/c_134265753.htm
New Drug Applications---Interesting page to keep your eye on:
http://www.drugs.com/new-drug-applications.html
INTERESTING---Alzheimer’s Disease Evolved With Human Intelligence in'Gazette Review', May 23, 2015
Excerpts:
"A new study, which was published in BioRxiv, shows that researchers are coming to the conclusion that Alzheimer’s disease has evolved with human intelligence. The study has found that between 50,000 and 200,000 years ago, natural selection ended up changing six genes that were involved in the development of the human brain. These changes could have increased the neurons connectivity, which is important for making humans smarter as they evolved from their hominin ancestors. However, the increases in intellectual capacity did come with some negative effects, such as those genes being blamed for Alzheimer’s disease.
Kun Tang, who is a population geneticist at Shanghai Institutes for Biological Sciences in China led the study, and Tang is speculating that as the aging brains struggled with the new metabolic demands by the increased intelligence, Alzheimer’s disease developed out of that. The only people or animal known to have Alzheimer’s disease is people, and it’s even absent in the closely related primates like Chimpanzees, so there is something in the human genes that have allowed Alzheimer’s to manifest. This is the first study to really determine that there are possibilities within evolution that could be responsible for Alzheimer’s disease, which opens the door for doctors to look at other treatment option"
"What is the most interesting about this new approach is that it can look at the African people, who go back further in time than the Asian or European people. Asian and Europeans were thought to come from only a small group of people who left about 60,000 years ago. Since Tang’s method allows you to go back further in time, you can look at the genomic-analysis of Africans from over 300,000 years ago. This new method will allow researchers to look at the evolutionary development of humans in a new way, especially when things like natural selection and population changes can be accounted for. The researchers are hoping that this new method will be able to be used in a broader way across all types of scientific situations, including evolutionary changes in animals or other groups of people. There is also hope that doing things like this can not only find out how Alzheimer’s disease happened, but a lot of other neurological and health conditions that impact millions of Americans and people all over the world. If researchers can find the genes behind other types of medical issues, then there would be new ways to look at treatment, and there could be new revolutionary treatments available for diseases that we did not think could be changed through modifying molecules."
Article at:
http://gazettereview.com/2015/05/alzheimers-disease-evolved-with-human-intelligence/
Google's Calico continues its partnering romp on aging R&D with Buck collaboration in 'Fierce Biotech Research', John Carroll, April 28, 2015
Excerpts:
"Google's stealthy biotech Calico is setting up shop inside the Buck Institute for Research on Aging in Novato, CA, after hammering out the latest in a long lineup of deals to collaborate on a new generation of therapeutics.
For South San Francisco-based Calico, the deal gives the biotech a chance to fund new work on projects "ranging from basic biology to potential therapies for age-related diseases," which is Calico's area of expertise. Calico in turn will get an exclusive option on the rights to any discoveries made in the collaboration, with the biotech establishing its own operations at the Buck.
Calico, which is headed by the legendary Art Levinson of Genentech fame, has rapidly spread its research tentacles into a range of institutes in search of crafting together a major pipeline of new drugs, all with the financial backing of Google ($GOOG), which has some of the deepest pockets on the planet."
""Given the Buck's exclusive focus on aging, we believe that there's great potential to increase our understanding of the biology of aging and to accelerate the translation of emerging insights into therapies to help patients with age-related diseases," noted Calico R&D chief Hal Barron in a statement"
Article at:
http://www.fiercebiotechresearch.com/story/googles-calico-continues-its-partnering-romp-aging-rd-buck-collaboration/2015-04-28
FDA warns about new class of diabetes drugs in 'Fox News', Dr. David B. Samadi, May 17, 2015
Excerpts:
"The U.S. Food and Drug Administration (FDA) issued a warning Friday that a widely used new class of type 2 diabetes drugs may cause high levels of blood acids dangerous enough to put people in the emergency room.
The new class of type 2 diabetes drugs are a group of oral medications called SGLT2 inhibitors, which work by helping the kidneys to lower blood glucose levels and blood sugar to be secreted in the urine. This prevents the kidneys from reabsorbing glucose back into the blood, thereby lowering blood glucose levels. A possible side effect of these drugs is actually weight loss.
SGLT2 inhibitors are recommended for people with type 2 diabetes who have high blood glucose levels regardless of being on medications like metformin and insulin.
However, there are certain side effects that are potentially dangerous. The FDA says the drugs may cause diabetic ketoacidosis, which results from a shortage of insulin"
Article and video at:
http://www.foxnews.com/health/2015/05/17/fda-warns-about-new-class-diabetes-drugs/?intcmp=ob_article_sidebar_video&intcmp=obinsite
Amgen Dumps Autoimmune Drug in Forbes, Luke Timmerman, 23 May 2015
News Article:
"Biotech giant Amgen said Friday that it was dropping out of a collaboration with AstraZeneca to co-develop brodalumab, an experimental drug designed to inhibit an inflammatory protein called IL-17. The drug has been designed to treat chronic conditions like psoriasis, psoriatic arthritis, and ankylosing spondylitis. Amgen walked away after it saw “events of suicidal ideation and behavior” in patients in clinical trials. That could be a show-stopper, especially for a drug that would be taken on a chronic basis."
Article at:
http://www.forbes.com/sites/luketimmerman/2015/05/23/what-you-may-have-missed-in-biotech-eye-drug-fails-ear-drug-flops-and-herpes-drug-succeeds/2/?ss=pharma-healthcare
Believe It or Not – the Cell Phone Alzheimer’s Treatment in 'A Journey Through Dementia', Kenneth Capron, May 23, 2015
My comments: Remember, there are people exploring ultrasound also. I wonder if they have surveyed heavy cell phone users to see if they have less Alzheimers?
Excerpts:
"OMG! It’s Smart Meters all over again. Would you believe that radio waves generated by cell phones could treat Alzheimer’s? According to one report (2009), when RF waves are directed inward at accumulated Beta Amyloid plaques, the plaques break down – at least in mice with Alzheimer’s."
"“Despite numerous studies, there is no definitive evidence that high-frequency electromagnetic field (EMF) exposure is a risk to human health. To the contrary, this report presents the first evidence that long-term EMF exposure directly associated with cell phone use (918 MHz; 0.25 W/kg) provides cognitive benefits. Both cognitive-protective and cognitive-enhancing effects of EMF exposure were discovered for both normal mice and transgenic mice”."
Article at:
http://journeythroughdementia.bangordailynews.com/2015/05/23/home/believe-it-or-not-the-cell-phone-alzheimers-treatment/
Tumeric-Curcumin
What is Curcumin? in Curcumin for Health.
My comments: Long article discussing the benefits of Curcumin. If you read the article, you might think it is about anatabine citrate. It is about Curcumin, an extract from the Tumeric root. After reading this article, one might wonder what Michael Mullan knows about Curcumin? Curcumin aids existing cancer drugs and treatments. It seems to have beneficial effects for autoimmune and chronic-inflammatory related diseases. Might Curcumin be a cheaper and maybe as effective solution as anatabine? Since it is natural, obviously it is not patentable so drug companies won't be pushing it anytime soon---having said that, maybe they might add it to their drug to get better benefit and maybe less toxicity? Might the fact that Curcumin exists be the reason Mullan is having no takers, that we know of, so far in licensing or joint venturing with RCPI? But again, maybe anatabine citrate is a more powerful agent than Curcumin? This article and others over the last 5 years are more and more pointing out the obvious that 'chronic inflammation' is a principal constituent of many diseases. Very little has been done to demonstrate what happens when chronic inflammation is curtailed? Does the problem go away? Do you get remission? In my opinion, well worth the read to help us understand possibilities.
Article at:
http://www.curcuminforhealth.com/all-in-one-solution/
Inflammation: A Common Denominator of Disease, Raymond Francis
Excerpts:
"Inflammation is one of the common denominators of disease. Every chronic disease is an inflammatory disease. No matter what so-called disease you have, from cancer to the common cold, inflammation is a major part of your problem. Learning how to prevent and reverse inflammation will go a long way toward preventing and reversing almost all disease, as well as slowing the aging process, keeping us healthy, biologically young and vigorous for a lifetime.
Unfortunately, most Americans suffer from chronic inflammation, caused by a variety of factors that seriously undermine health and ages us prematurely. Resulting from an “inflammatory cascade,” common inflammatory diseases include allergies, Alzheimer’s, asthma, arthritis, autoimmune diseases, bursitis, cancer, cervicitis, colitis, cystitis, diabetes, gastritis, heart disease, hepatitis, infections, myocarditis, nephritis, neuritis, osteoporosis, prostatitis, sinusitis, tendonitis, and vaginitis. Even our children are increasingly suffering from “diseases of aging” in epidemic numbers. To put an end to this tragedy, we must learn how to prevent and reverse chronic inflammation."
"What causes inflammation? Most importantly, the standard American diet causes inflammation. Most of us suffer from chronic inflammation and disease because the American diet is pro-inflammatory. It is rich in pro-inflammatory compounds, while lacking antioxidants and other nutrients that help to prevent and control inflammation.
How does our diet cause inflammation? One way is our excessive consumption of refined carbohydrates. Sugar and white flour are deadly poisons that have an inflammatory effect on the body. Unaware of this, the average American consumes more than 160 pounds of sugar and 200 pounds of white flour per year. Sugar and white flour increase blood sugar, and even a modest increase in blood sugar generates pro-inflammatory chemicals. Most people eat these poisons daily in the form of bread, pasta, breakfast cereal, cookies, cakes, soft drinks, candy, etc.
In addition, sugar and white flour cause inflammation and disease by forming AGEs.
AGEs are produced when a protein reacts with sugar, resulting in damaged, cross-linked proteins. As the body tries to protect you by breaking these AGEs apart, immune cells secrete large amounts of inflammatory chemicals. Many of the diseases that we think of as part of aging are actually caused by this process. Depending on where the AGEs occur, the result can be arthritis, heart disease, cataracts, memory loss, wrinkled skin or diabetes complications, to name a few."
"Yet another promoter of chronic, systemic inflammation is fat cells. More than two-out-of-three Americans are overweight, and fat cells, especially those that form around the abdomen, produce large amounts of inflammatory chemicals. This is a huge source of inflammation, and is the reason why overweight people suffer so much more disease and disability.
Environmental toxins are also inflammatory. Synthetic fibers, latex, glues, adhesives, plastics, air fresheners, cleaning products and perfume are examples of everyday chemicals that can trigger an inflammatory response. Chronic exposure, at even low doses, can drive your immune system crazy, resulting in inflammatory autoimmune diseases.
Chronic stress produces hormones that result in chronic inflammation. Stress produces inflammatory chemicals that can make your skin break out or your intestines go into revolt. Likewise, insomnia causes inflammation. People who are sleep deprived have higher levels of inflammatory chemicals.
Inflammation is a common element in virtually all disease. By causing chronic inflammation we are aging ourselves prematurely, causing us to look old, feel tired, and suffer every imaginable disease. Controlling chronic inflammation takes a combination approach because it arises from a combination of causes, but most of it is under your control. By learning how to prevent and reverse inflammation, you can achieve power over aging and disease. What a wonderful goal – and so easy to do."
Article at:
http://arizonaadvancedmedicine.com/inflammation-a-common-denominator-of-disease/
Drug prices to treat multiple sclerosis soar, point to larger problem in World Pharma News, 28 APRIL 2015
Excerpts:
"A new study found that drugs used to treat multiple sclerosis have soared in price in the past two decades, in some cases more than 700 percent, even though newer drugs have come to the market - a process that normally should have stabilized or reduced the cost of at least the older medications.
There are no multiple sclerosis drugs now available in the United States with a list price below $50,000 a year, which is two to three times more than the price in Canada, Australia or the United Kingdom. The group of drugs available to treat this disease is rising in price at five to seven times the normal rate of drug inflation in the U.S."
"Escalating costs for specialty pharmaceuticals, for conditions such as multiple sclerosis, cancer, and hepatitis C, have been a growing concern among many in the health care industry, the authors wrote in their study, raising questions about the ethics of our current approach, exorbitant pricing and increased burdens on "our already stressed healthcare system.""
"In the specific case of multiple sclerosis, the research looked at first-generation drugs which became available in the 1990s at prices ranging from $8,000 to $10,000 a year. More competition from other drugs then entered the field. But instead of the price of the original drugs staying about the same or going down, as classic economic theory might dictate, their price soared. One drug that originally cost $8,700 now costs $62,400 a year."
Article at:
http://www.worldpharmanews.com/research/3075-drug-prices-to-treat-multiple-sclerosis-soar-point-to-larger-problem
Scientists find new link between diabetes and Alzheimer's in World Pharma News, 05 MAY 2015
Excerpts:
"Researchers have uncovered a unique connection between diabetes and Alzheimer's disease, providing further evidence that a disease that robs people of their memories may be affected by elevated blood sugar, according to scientists at Washington University School of Medicine in St. Louis.
While many earlier studies have pointed to diabetes as a possible contributor to Alzheimer's, the new study - in mice - shows that elevated glucose in the blood can rapidly increase levels of amyloid beta, a key component of brain plaques in Alzheimer's patients. The buildup of plaques is thought to be an early driver of the complex set of changes that Alzheimer's causes in the brain."
"In young mice without amyloid plaques in their brains, doubling glucose levels in the blood increased amyloid beta levels in the brain by 20 percent.
When the scientists repeated the experiment in older mice that already had developed brain plaques, amyloid beta levels rose by 40 percent."
Article at:
http://www.worldpharmanews.com/research/3080-scientists-find-new-link-between-diabetes-and-alzheimers
Boehringer Ingelheim acquires Pharmaxis' phase 1 anti-inflammatory drug candidate, 19 MAY 2015
Excerpts:
"Boehringer Ingelheim and pharmaceutical company Pharmaxis (ASX: PXS) announce that Boehringer Ingelheim has exercised its option and acquired the investigational drug PXS4728A, to develop it for the treatment of the liver-related condition NASH and to prevent its consequences. PXS4728A is a Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 (SSAO/VAP-1) Inhibitor discovered by Pharmaxis that works by blocking leucocyte adhesion and tissue infiltration in inflammatory processes. Pharmaxis has developed it through to phase 1 clinical studies, demonstrating oral bioavailability, long-lasting target inhibition and good tolerability and safety.
NASH is the progressive form of non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in Western industrialized nations. It is regarded as a major cause of fibrosis and cirrhosis of the liver and is an area of high unmet clinical need. The high prevalence of type 2 diabetes and obesity, which can lead to NASH and its long term consequences, is considered to make NASH one of the most common causes of advanced liver disorders in coming decades."
"Pharmaxis CEO Mr Gary Phillips said, "This is a transformational event for Pharmaxis. With a total potential value in excess of $A750 million, it is a globally competitive deal and significant for the Australian biotech sector. We are delighted that Boehringer Ingelheim, a leader in cardiometabolic research and development, has acquired PXS4728A. Boehringer Ingelheim’s clinical expertise will now be applied to the development of this drug which has the potential to make a real difference in the treatment of diseases with high unmet clinical need."
Pharmaxis will receive an upfront payment of €27.5 million (approximately A$39m) and, subject to the continuing successful development and commercialisation of the PXS4728A program, the following payments:
up to a total of €55 million in development milestone payments tied to the commencement of phase 2 and 3 clinical trials
up to a total of €140 million in regulatory milestone payments upon filing of applications for marketing approval and receipt of regulatory and pricing approvals for a PXS4728A program product in the major pharmaceutical markets (i.e., USA, EU, and China or Japan) for the first indication
additional milestone payments similar in total to those set forth above upon achievement of the same development and regulatory milestone events by a PXS4728A program product for a second indication
earn-out payments on annual net sales of PXS4728A program products at tiered percentages starting in the high single digits
commercialisation milestone payments upon achievement of specified levels of annual net sales of PXS4728A program products"
"NASH is the progressive form of non-alcoholic fatty liver disease (NAFLD) which is the most common liver disorder in Western industrialized nations with an estimated 30% prevalence in the United States for NAFLD and 3-5% for NASH. NASH is regarded as a major cause of cirrhosis of the liver and is an area of high unmet clinical need. The high prevalence of type 2 diabetes and obesity, which can lead to NASH and other non-alcoholic fatty liver diseases, is expected to make NASH potentially the most common cause of advanced liver conditions in coming decades and the market has been estimated to exceed $3.5billion by 2025."
Article at:
http://www.worldpharmanews.com/boehringer-ingelheim/3090-boehringer-ingelheim-acquires-pharmaxis-phase-1-anti-inflammatory-drug-candidate
News Review From Harvard Medical School -- Study Tracks Amyloid Links to Dementia Risk, May 20, 2015
Excerpts:
"Deposits called amyloid plaques may appear in the brain 20 years or more before people develop signs of dementia, a research review finds. These plaques are more often found in older adults. But they also are seen more often in younger adults with a high risk of developing Alzheimer's disease, the study showed. The study was based on previous research. It included 1,359 people with diagnosed Alzheimer's disease, 538 people with other types of dementia and autopsy results for 1,369 others with Alzheimer's. The living subjects all had PET scans to look for amyloid plaques in the brain. Among those with normal memory and thinking skills, these plaques were more common with age. About 10% of 50-year-olds had them. That increased to 33% at age 80 and 44% at age 90. Some people carried the APOE4 gene variant, which is linked with a higher risk of Alzheimer's. People in this group were 2 to 3 times more likely to have amyloid plaques than those without the gene. People who already had mild memory issues were more likely to have plaques, and at earlier ages. The Journal of the American Medical Association published the study. HealthDay News wrote about it May 19. "
"One of the changes linked with a higher risk of developing Alzheimer's disease is a build-up of a protein called beta amyloid. However, about 12% of people with diagnosed Alzheimer's disease don't show amyloid deposits on brain scans. And about 30% of older people who continue to maintain excellent thinking and memory have heavy deposits of amyloid on a brain scan. "
"This new research found that highly educated people develop thinking and memory problems at an older age than those with less formal education. However, the highly educated people had more brain amyloid than those with less education. The researchers suggest that more education creates pathways in the brain to help preserve thinking and memory despite these amyloid deposits."
"The complex relationship between brain amyloid and Alzheimer's disease makes it very challenging to study anti-amyloid drugs. But it is probably our best shot at finding a treatment to reduce risk or at least slow the disease.
Recent studies of anti-amyloid drugs have been disappointing. However, it may be that they are being given after the damage is done. New studies are underway to start anti-amyloid drugs much earlier. People in these studies have deposits showing on brain scans but don't show signs of problems with thinking or memory."
Article at:
https://www.intelihealth.com/article/study-tracks-amyloid-links-to-dementia-risk
YES, because tobacco contains anatabine. Johnny Williams followed the trail when he found out that airline stewardesses had fewer Parkinsons related problems relative to the general public during the time when airlines allowed smoking. You might also want to try Marijuana salad---weed seems to have some beneficial attributes also. (checkout the recent copy of National Geographics:
http://ngm.nationalgeographic.com/
Is nicotine all bad? in Reuters Health, KATE KELLAND, Tue May 19, 2015
MY COMMENTS: So why not Anatabine for smoking cessation safer?
Excerpts:
"Some studies show nicotine, like caffeine, can even have positive effects. It's a stimulant, which raises the heart rate and increases the speed of sensory information processing, easing tension and sharpening the mind.
All this raises other questions: Could nicotine prime the brains of young people to seek harder stuff? Or, in an aging society, could its stimulant properties benefit people whose brains are slowing, warding off cognitive decline into Alzheimer’s and delaying the progression of Parkinson’s disease?
So far the answers aren’t clear. And the divide is as political and emotional as it is scientific"
"McNeill says her work is, in part, to honor the legacy of her former mentor at King's, British psychiatrist Mike Russell. About 40 years ago, Russell was one of the first scientists to suggest that people "smoke for the nicotine, but die from the tar" – an idea that helped lay the ground for the NRT business of gums, patches, vaporizers and now e-cigarettes."
"Smoking kills half of all those who do it - plus 600,000 people a year who don't, via second-hand smoke - making it the world's biggest preventable killer, with a predicted death toll of a billion by the end of the century, according to the World Health Organization."
"One reason smoking is so addictive is that it's a highly efficient nicotine delivery system, McNeill says. “Smoking a tobacco cigarette is one of the best ways of getting nicotine to the brain - it's faster even than intravenous injection." Also, tobacco companies used various chemicals to make the nicotine in cigarettes even more potent."
"Elsewhere, studies have looked at nicotine's potential to prevent Alzheimer's disease, and to delay the onset of Parkinson's.
A study in the journal Brain and Cognition in 2000 found that “nicotinic stimulation may have promise for improving both cognitive and motor aspects of Parkinson's disease.” Another, in Behavioral Brain Research, suggested “there is considerable potential for therapeutic applications in the near future.” Other work has looked at the stimulant's potential for easing symptoms of attention deficit hyperactivity disorder (ADHD)."
"Even so, the idea of "safe nicotine" has not caught on.
Marcus Munafo, a biological psychologist at Britain's Bristol University, says public health campaigns of the 1970s and 1980s bound nicotine, addiction and cigarettes tightly together to hammer home smoking's harms. Those associations may blur the potential for cleaner nicotine to lure smokers away from cigarettes."
Article at:
http://www.reuters.com/article/2015/05/19/us-health-nicotine-insight-idUSKBN0O412Q20150519?feedType=nl&feedName=healthNews
Rock Creek Pharmaceuticals $232770 Financing. Benjamin M Dent Filled May 18 form at OCTA Finance
Article:
"Rock Creek Pharmaceuticals Financing
Rock Creek Pharmaceuticals, Inc., Corporation just submitted form D for $232,770 equity financing. This is a new filing. Rock Creek Pharmaceuticals was able to finance itself with $232,770. That is 100.00% of the financing offer. The total offering amount was $232,770. The form was filled on 2015-05-18. The reason for the financing was: unspecified.
Rock Creek Pharmaceuticals is based in Florida. The firm’s business is not disclosed. The D form was submitted by Benjamin M Dent Chief Financial Officer. The company was incorporated more than five years ago. The filler’s address is: 2040 Whitfield Avenue, Suite 300, Sarasota, Fl, Florida, 34243. Michael J. Mullan is the related person in the form and it has address: 2040 Whitfield Avenue, Suite 300, Sarasota, Fl, Florida, 34243. Link to Rock Creek Pharmaceuticals Filing: 000114036115020808.
Analysis of Rock Creek Pharmaceuticals Offering
On average, firms in the not disclosed sector, sell 67.77% of the total offering amount. Rock Creek Pharmaceuticals sold 100.00% of the offering. Could this mean that the trust in Rock Creek Pharmaceuticals is high? The average fundraising amount for companies in all industries in our database is $3.05 million. The offering was 92.37% smaller than the average of $3.05 million. Of course this should not be interpreted as negative. Startups get financed for different needs and reasons. The minimum investment for this financing is set at $0. If you know more about the reasons for the financing, please comment below.
What is Form D? What It Is Used For
Form D disclosures could be used to track and understand better your competitors. The information in Form D is usually highly confidential for ventures and startups and they don’t like revealing it. This is because it reveals amount raised or planned to be raised as well as reasons for the financing. This could help competitors. Entrepreneurs usually want to keep their financing a ‘secret’ so they can stay in stealth mode for longer.
Why Fundraising Reporting Is Good For Rock Creek Pharmaceuticals Also
The Form D signed by Benjamin M Dent might help Rock Creek Pharmaceuticals, Inc.’s business. First, it helps potential customers feel more safe to deal with a firm that is well financed. The odds are higher that it will stay in the business. Second, this could attract other investors such as venture-capital firms, funds and angels. Third, positive PR effects could even bring leasing firms and venture lenders."
Article at:
http://www.octafinance.com/rock-creek-pharmaceuticals-232770-financing-benjamin-m-dent-filled-may-18-form/
BINGO!---"In this article we make the case for the role of glia in the pathophysiology of delirium and describe an astrocyte-dependent central and peripheral cholinergic anti-inflammatory shield which may be disabled by astrocytic pathology, leading to neuroinflammation and delirium."
Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation.
Paris D1, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C, Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M.
"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."
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/23178521
If you Google Wikipedia for 'Microglia', you'll find an interesting discourse as applied to AD:
http://en.wikipedia.org/wiki/Microglia
Excerpts:
"Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system (CNS).
Microglia constitute 10-15% of all cells found within the brain.[1] Microglia (and astrocytes) are distributed in large non-overlapping regions throughout the brain and spinal cord.[2][3] Microglia are constantly scavenging the CNS for plaques, damaged neurons and infectious agents.[4] The brain and spinal cord are considered "immune privileged" organs in that they are separated from the rest of the body by a series of endothelial cells known as the blood–brain barrier, which prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood–brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (few antibodies are small enough to cross the blood brain barrier), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells. Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.[5] They achieve this sensitivity in part by having unique potassium channels that respond to even small changes in extracellular potassium.[4]"
"Role in chronic neuroinflammation[edit]
The word neuroinflammation has come to stand for chronic, central nervous system (CNS) specific, inflammation-like glial responses that may produce neurodegenerative symptoms such as plaque formation, dystrophic neurite growth, and excessive tau phosphorylation.[16] It is important to distinguish between acute and chronic neuroinflammation. Acute neuroinflammation is generally caused by some neuronal injury after which microglia migrate to the injured site engulfing dead cells and debris.[16] The term neuroinflammation generally refers to more chronic, sustained injury when the responses of microglial cells contribute to and expand the neurodestructive effects, worsening the disease process.[16]
When microglia are activated they take on an amoeboid shape and they alter their gene expression. Altered gene expression leads to the production of numerous potentially neurotoxic mediators. These mediators are important in the normal functions of microglia and their production is usually decreased once their task is complete.[17] In chronic neuroinflammation, microglia remain activated for an extended period during which the production of mediators is sustained longer than usual.[17] This increase in mediators contributes to neuronal death.[17]
Neuroinflammation is distinct from inflammation in other organs, but does include some similar mechanisms such as the localized production of chemoattractant molecules to the site of inflammation.[17] The following list contains a few of the numerous substances that are secreted when microglia are activated:
Cytokines[edit]
Microglia activate the proinflammatory cytokines IL-1a, IL-1ß and TNF-a in the CNS.[17] Cytokines play a potential role in neurodegeneration when microglia remain in a sustained activated state.[17] Direct injection of the cytokines IL-1a, IL-1ß and TNF-a into the CNS result in local inflammatory responses and neuronal degradation.[17] This is in contrast with the potential neurotrophic (inducing growth of neurons) actions of these cytokines during acute neuroinflammation.[17]
Chemokines[edit]
Chemokines are cytokines that stimulate directional migration of inflammatory cells in vitro and in vivo.[17] Chemokines are divided into four main subfamilies: C, CC, CXC, and CX3C. Microglial cells are sources of some chemokines and express the monocyte chemoattractant protein-1 (MCP-1) chemokine in particular.[17] Other inflammatory cytokines like IL-1ß and TNF-a, as well as bacterial-derived lipopolysaccharide (LPS) may stimulate microglia to produce MCP-1, MIP-1a, and MIP-1ß.[17] Microglia can express CCR3, CCR5, CXCR4, and CX3CR1 in vitro.[17] Chemokines are proinflammatory and therefore contribute to the neuroinflammation process.[17]
Proteases[edit]
When microglia are activated they induce the synthesis and secretion of proteolytic enzymes that are potentially involved in many functions.[17] There are a number of proteases that possess the potential to degrade both the extracellular matrix and neuronal cells that are in the neighborhood of the microglia releasing these compounds.[17] These proteases include; cathepsins B, L, and S, the matrix metalloproteinases MMP-1, MMP-2, MMP-3, and MMP-9, and the metalloprotease-disintegrin ADAM8 (plasminogen) which forms outside microglia and degrades the extracellular matrix.[17] Both Cathepsin B, MMP-1 and MMP-3 have been found to be increased in Alzheimer's disease (AD) and cathepsin B is increased in multiple sclerosis (MS).[17] Elastase, another protease, could have large negative effects on the extracellular matrix.[17]
Amyloid precursor protein[edit]
Microglia synthesize amyloid precursor protein (APP) in response to excitotoxic injury.[17] Plaques result from abnormal proteolytic cleavage of membrane bound APP.[17] Amyloid plaques can stimulate microglia to produce neurotoxic compounds such as cytokines, excitotoxin, nitric oxide and lipophylic amines, which all cause neural damage.[18] Plaques in Alzheimer's disease contain activated microglia.[17] A study has shown that direct injection of amyloid into brain tissue activates microglia, which reduces the number of neurons.[18] Microglia have also been suggested as a possible source of secreted ß amyloid.[17]"
"Role of microglia in neurodegeneration[edit]
Neurodegenerative disorders are characterized by progressive cell loss in specific neuronal populations.[17] "Many of the normal trophic functions of glia may be lost or overwhelmed when the cells become chronically activated in progressive neurodegenerative disorders, for there is abundant evidence that in such disorders, activated glia play destructive roles by direct and indirect inflammatory attack."[17] The following are prominent examples of microglial cells' role in neurodegenerative disorders.
Alzheimer's disease[edit]
Alzheimer's disease (AD) is a progressive, neurodegenerative disease where the brain develops abnormal clumps (amyloid plaques) and tangled fiber bundles (neurofibrillary tangles).[20]
There are many activated microglia over-expressing IL-1 in the brains of Alzheimer patients that are distributed with both Aß plaques and neurofibrillary tangles.[19] This over expression of IL-1 leads to excessive tau phosphorylation that is related to tangle development in Alzheimer's disease.[19]
Many activated microglia are found to be associated with amyloid deposits in the brains of Alzheimer's patients.[17] Microglia interact with ß-amyloid plaques through cell surface receptors that are linked to tyrosine kinase based signaling cascades that induce inflammation.[17] When microglia interact with the deposited fibrillar forms of ß-amyloid it leads to the conversion of the microglia into an activated cell and results in the synthesis and secretion of cytokines and other proteins that are neurotoxic.[17]
One preliminary model as to how this would occur involves a positive feedback loop. When activated, microglia will secrete proteases, cytokines, and reactive oxygen species. The cytokines may induce neighboring cells to synthesize amyloid precursor protein. The proteases then possibly could cause the cleaving required to turn precursor molecules into the beta amyloid that characterizes the disease. Then, the oxygen species encourage the aggregation of beta amyloid in order to form plaques. The growing size of these plaques then in turn triggers the action of even more microglia, which then secrete more cytokines, proteases, and oxygen species, thus amplifying the neurodegeneration.[21]
Treatment[edit]
Non-steroidal anti-inflammatory drugs (NSAIDs) have proven to be effective in reducing the risk of AD.[17] "Sustained treatment with NSAIDs lowers the risk of AD by 55%, delays disease onset, attenuates symptomatic severity and slows the loss of cognitive abilities. The main cellular target for NSAIDs is thought to be microglia. This is supported by the fact that in patients taking NSAIDs the number of activated microglia is decreased by 65%."[17]
Parkinson's disease[edit]
Parkinson's disease is a movement disorder in which the dopamine-producing neurons in the brain do not function as they should, the neurons of the Substantia Nigra become dysfunctional and eventually die, leaving a lack of dopamine input into the striatum. This causes the symptoms of Parkinson's disease.[22]
Cardiovascular Diseases[edit]
Recently microglial activation has been reported in rats with myocardial infarction (Rana et al.,2010). This activation was specific to brain nuclei involved in cardiovascular regulation suggesting possible role of microglial activation in pathogenesis of heart failure."
"As a target to treat neuroinflammation[edit]
Inhibition of activation[edit]
One way to control neuroinflammation is to inhibit microglial activation. Studies on microglia have shown that they are activated by diverse stimuli but they are dependent on activation of mitogen-activated protein kinase (MAPK).[17] Previous approaches to down-regulate activated microglia focused on immunosuppressants.[17] Recently, minocycline (a tetracycline derivative) has shown down-regulation of microglial MAPK.[17] Another promising treatment is CPI-1189, which induces cell death in a TNF a-inhibiting compound that also down-regulates MAPK.[17] Recent study shows that nicergoline (Sermion) suppresses the production of proinflammatory cytokines and superoxide anion by activated microglia.[39] Microglial activation can be inhibited by MIF (microglia/macrophage inhibitory factor, tuftsin fragment 1–3, Thr-Lys-Pro). MIF-treated mice showed reduced brain injury and improved neurologic function in a mouse model of collagenase-induced intracerebral hemorrhage.[40][41
Regulation of chemokine receptor[edit]
The chemokine receptor, CX3CR1, is expressed by microglia in the central nervous system.[42] Fractalkine (CX3CL1) is the exclusive ligand for CX3CR1 and is made as a transmembrane glycoprotein from which a chemokine can be released.[42] Cardona, et al. stated in 2006 that "using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity."[42] Further studies into how CX3CR1 regulates microglial neurotoxicity could lead to new therapeutic strategies for neuroprotection.[42]
Inhibition of amyloid deposition[edit]
Inhibitors of amyloid deposition include the enzymes responsible for the production of extracellular amyloid such as ß-secretase and ?-secretase inhibitors.[17] Currently the ?-secretase inhibitors are in phase II clinical trials as a treatment for Alzheimer's disease but they have immunosuppressive properties, which could limit their use.[17] Another strategy involves increasing the antibodies against a fragment of amyloid.[17] This treatment is also in phase II clinical trials for the treatment of Alzheimer's disease.[17]
Inhibition of cytokine synthesis[edit]
Glucocorticosteroids (GCS) are anti-inflammatory steroids that inhibit both central and peripheral cytokine synthesis and action.[17] In a study conducted by Kalipada Pahan from the Department of Pediatrics at the Medical University of South Carolina, both lovastatin and sodium phenylacetate were found to inhibit TNF-a, IL-1ß, and IL-6 in rat microglia.[43] This shows that the mevalonate pathway plays a role in controlling the expression of cytokines in microglia and may be important in developing drugs to treat neurodegenerative diseases.[43] Naltrexone may provide a solution to the inflammatory mediators produced by microglia. Although naltrexone's main action is to competitively bind to opioid receptors, new research shows that naltrexone, when given in low doses once per day (low-dose naltrexone), can inhibit cytokine synthesis by microglia cells. This mechanism is still being investigated, but there are already studies that indicate that it helps some patients suffering from fibromyalgia syndrome. Naltrexone shows more promise than GCSs because the GCSs inhibit immune system function more generally, increase allergic reactions and, as the name implies, increase blood glucose levels.[44][45]"
From the RCPI Website:
"EUROPEAN JOURNAL OF PHARMACOLOGY Volume 670, Issues 2–3, November 30, 2011, Pages 384–391
Abstract:
Brain Aß accumulation represents a key pathological hallmark in Alzheimer's disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on Aß production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer's disease. In vitro, anatabine lowers Aß1–40 and Aß1–42 levels in a dose dependent manner and reduces sAPPß production without impacting sAPPa levels suggesting that anatabine lowers Aß production by mainly impacting the ß-cleavage of APP. Additionally, we show that anatabine lowers NF?B activation at doses that inhibit Aß production in vitro. 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://rockcreekpharmaceuticals.com/html/article_5.php
However he did say: "The inflammation drugs, we could get lucky because we know exactly what we need to do, we need to stop this gene, CD33. So I think that’s maybe 10 to 15 years out."
Maybe he is thinking if you stop plaque, you won't get tangles and if they don't exist or are reduced, you won't get inflammation? If so, why would you develop an inflammation drug?
Certainly prevention is very important---but what happens with the patients who already have plaques and tangles already?
Obviously 'inflammation' is becomming more and more recognized and an important issue with autoimmune and related diseases.
Very interesting article, especially the part:
"We know from autopsies people who died cognitively intact — no dementia in their 80s — yet with brains full of plaques and tangles. You ask what protected them: They didn’t have inflammation."
"So just this year, we came to the realization that genes involved in the immune system control inflammation in the brain, and seem to be the final piece of the puzzle. First you get plaque, then tangles, then that inflammation really pushes you over the slippery slope into dementia. All this says if you have a drug cocktail where you stop amyloid, you prevent the tangles, you chill out inflammation, then you’ll stop this disease."
My comments: Tanzi said that seniors in their 80's HAD brains full of plaques and tangles but no dementia.---Missing was inflammation. But then he goes on to say you get plaques and tangles then inflammation to get dementia. Sounds to me like his comment that, like Biogen is trying to do, stop the plaque first may still have a problem if you still get inflammation.???? Or is he saying if you stop plaques, you won't get inflammation???
100 Best-Selling, Most Prescribed Branded Drugs Through March, Troy Brown, RN, May 06, 2015
Excerpts:
"The hypothyroid drug levothyroxine (Synthroid, AbbVie) was the most prescribed drug in the United States, and the arthritis drug adalimumab (Humira, Abbott Laboratories) was the best-selling drug through March of this year, according to recent data."
"Levothyroxine had about 21.6 million prescriptions, followed by cholesterol-lowering drug rosuvastatin (Crestor, AstraZeneca), at about 21.5 million "
"The arthritis drug adalimumab (Humira, Abbott Laboratories) had sales of about $8.3 billion, followed by the antipsychotic medication aripiprazole (Abilify, Otsuka Pharmaceutical) at $8 billion"
Article at:
http://www.medscape.com/viewarticle/844317#vp_1
My comments: So thyroid and arthritis drugs are at the top of the list. RCPI research targets include: Osteoarthritis, Ulcerative Colitis, Psoriasis, Smoking Cessation, and Hashimoto's Thyroiditis. The RCPI targets includes the top drugs on the 'most prescribed' and 'best-selling' lists. Not to mention the potential elephant in the room: Alzheimers.'
U.S., Chinese researchers find potential drug target for Parkinson's disease, Xinhua News Agency, May 12, 2015
Excerpt:
"In a study published in the U.S. journal Science Signaling, the researchers found that misfolded -synuclein can activate immune cells' Toll-like receptors (TLR) 1 and 2 to trigger inflammation and that preventing this inflammation is the key to controlling neurological diseases.
The real job of TLR1/2 is to protect our bodies by getting rid of invading pathogens, said study author Yin Hang, professor of Tsinghua University, but misfolded -synuclein caused them to overreact, leading to long-term chronic inflammation which damages the brain.
The findings were based on the research of microglia, cells that act as the main form of immune defense in the central nervous system.
Yin's team, in collaboration with researchers at the Georgetown University, also showed that a new small molecule compound called CU-CPT22, which specifically targets TLR1/2, can significantly reduce this inflammation."
Article at:
http://www.globalpost.com/article/6546518/2015/05/12/us-chinese-researchers-find-potential-drug-target-parkinsons-disease
Rock Creek Pharmaceuticals Reports First Quarter 2015 Results and Provides Clinical Update at:
http://investors.rockcreekpharmaceuticals.com/index.php?s=43&item=201#assets_3
Excerpt:
"
Michael J. Mullan, MBBS (MD), PhD, Chairman and CEO of Rock Creek Pharmaceuticals, remarked, "We advanced several strategic objectives in the first quarter, having commenced and significantly progressed through our human Phase I studies in the United Kingdom, completed our study in New Zealand, as well as having moved forward with various corporate development initiatives. The Company significantly slowed its cash burn, after successfully restructuring into a more appropriate platform for drug discovery and clinical development of our compounds. Concurrently the Company is planning for Phase II trials, exploring potential in-licensing/out-licensing opportunities, as well as advancing towards achieving a more secure financial footing.""
My opinion: The FDA is putting the screws on non-pharmaceutical drug companies to spend large amounts of money up front to get 'proof' data on efficacy and safety of new products and ingredients. This should stop small companies from developing new (ingredients) non-drug products and force them to drop out of competition with 'Big Pharma' for treating ailments. Mullan appears to recognize that hurdle, hence the effort in Europe to demonstrate 'safety' and some efficacy with the clinical trials there. With this in hand, he should be able to, without a doubt, prove Anatabine Citrate use as both a drug and nutraceutical. (my opinion: he will resubmit the NDI with the FDA with this data as 'proof'). (apparently the FDA does not recognize the word nutraceutical, only the Europeans do). So---before end of June we should know whether we are 'pass' or 'fail'. My money is on 'pass' because of all the previous testing. The European clinical trials appears to be a dog and pony show for the FDA so they don't lose face. It also may give RCPI momentum and recognition in Europe. I wonder how many other companies will jump this high wall to prove new 'natural' molecule products? Have you noticed that 'Big Pharma' is moving into the vitamin/health supplement arena very quietly? (they have also ramped up efforts on chronic inflammation---surprise, surprise) This playbook follows in the steps of Stevia. Stevia has been used as a sweetener in Japan for over 40 years with a very safe record. Even longer in South America. Both Japan and South Americans thought Stevia was a food product but here in the United States, only after the big guys like Cargill (think sugar monopoly) and Coca Cola got their positions lined up did Stevia become mainstream by the FDA as a 'food product'(last sentence in article.---For shame! Money talks in the United States and government 'for the people and by the people shall perish from this earth'. So, place your bets!
See:
http://www.foxnews.com/story/2009/06/10/many-vitamins-supplements-made-by-big-pharmaceutical-companies/
http://bodyecology.com/articles/brief_history_of_stevia.php
http://www.stevia.net/history.htm
Before filing a suit, review the FDA outline for NDI and you will NOT find 'Anatabine Citrate' on the list. See:
http://www.fda.gov/Food/DietarySupplements/ucm109764.htm
How Star Scientific's FDA 'experts' didn't know this before they sold Anatabloc as a dietary supplement escapes me? The FDA directive clearly states that while they don't regulate supplements, they do approve ingredients to assure 'safety'. Having said that, the FDA only provided a 'draft' guidance in July of 2011 for manufacturers to follow:
"When must I notify FDA about a new dietary ingredient?
The FD&C Act provides that a dietary supplement that contains a new dietary ingredient shall be deemed adulterated under section 402(f) of the FD&C Act (21 U.S.C. 342(f)) unless it meets one of two requirements:
The dietary supplement contains only dietary ingredients which have been present in the food supply as an article used for food in a form in which the food has not been chemically altered; or
There is a history of use or other evidence of safety establishing that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe and, at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides the FDA with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe."
It would seem Star's claim of a 'natural, contained in existing foods' sounded ok to many of us but we are not the FDA. Did Star have dialogue with the FDA before commencing sales? The circumstantial evidence doesn't look like it. It would appear Star 'guessed' at the 'natural, so OK to sell without an NDI. Tobacco is not considered a food or vitamin. The amount of anatabine found in nightshade plants are miniscule. I emphasize with those who NEED Anatabloc but I feel we are in better hands now with Dr Mullan etal and need to keep moving forward.
RCPI Lawsuit commentary on CIGX VIPGROUP message board:
<CIGX_VIPGROUP@yahoogroups.com>
4:39 PM (8 minutes ago)
"Well, I got my copy (4 of them actually) of the Class Action lawsuit proposed settlement. I suppose this has been discussed at length on the clown board, but I quit reading it years ago and haven’t the patience to wade through it, so as briefly as I can I’ll go through my understanding of it and if anyone following this forum spots any errors or significant omissions I hope you will let me know.
It appears to me the insurance company has opted to approve this settlement just to get rid of the case, and as a qualified investor, if I elect to join it I’m entitled to a pro rata share. Unless that share is less than $5.00, in which case I get nothing. Whether I do or don’t join, it makes no difference to Rock Creek, but will have the effect of reducing the amount all the other and qualifying share purchasers receive. So, for that reason as much as any other I guess I’ll sign up.
Lest anyone think otherwise, I think the lawsuit is completely without merit, and it galls me that the plaintiff’s lawyers (i.e. my lawyers!) are going to walk away with their fee plus expenses. I do have the option of filing a statement objecting to the settlement, but I have to assume the defence has done the best they can to restrict the damage, and anything I do will be just so much clutter. I think it’s a serious weakness of the legal system that lawyers can actually make money pursuing cases without merit simply because it’s cheaper for the defendant to settle than to see the case through to an accurate conclusion. I’d complain to my congressperson if I had one! (I’m Canadian)
The class action lawsuit I would really love to see and join would be one against the FDA for forcing Anatabloc off the market. “Do no harm” is the credo of physicians generally, and they must know they are doing substantial harm with this policy. I know many users, perhaps many who are reading this, are enduring consequences far more severe than mine, but that gives me no comfort whatsoever. I’ve just endured my worst hay fever season in more than 25 years; the Anatabloc worked just as well as the shots I was taking so I quit taking the shots and didn’t think to resume them when my Abloc ran out. Oh well, at least my arthritis hasn’t come back on me. Not yet.
I’ll take this opportunity and say “Thank you” to those who, unlike me, do post useful information here. Especially Isof. You probably don’t hear it often enough, but your efforts are appreciated.
Regards
Smokey"
Astaxanthin Plays Anti-inflammatory and Antioxidant Effects by Inhibiting NFkB Nuclear Translocation and NOX2 Expression in Macrophages in 'The Journal of the Federation of American Societies for Experimental Biology', Callie Farruggia1, Yue Yang1, Bohkyung Kim1, Tho Pham1, Minkyung Bae1, Young-Ki Park1 and Ji-Young Lee1, Department of Nutritional Sciences University of Connecticut Storrs CT United States
Abstract
"Chronic inflammation and oxidative stress are associated with obesity-related metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. Astaxanthin (ASTX), a xanthophyll carotenoid, has been suggested to play anti-inflammatory and antioxidant functions. We investigated potential mechanisms of action by which ASTX exerts the anti-inflammatory and antioxidant effects in macrophages. When RAW 264.7 macrophages were stimulated by LPS (100 ng/ml) for 24 h, mRNA expression of IL-6 and IL-1ß was increased. However, co-incubation with ASTX (25 mM) significantly attenuated the induction. ASTX markedly decreased LPS-induced nuclear translocation of nuclear factor kB (NFkB). In addition, LPS increased cellular reactive oxygen species (ROS), which was abolished by ASTX with a concomitant decrease in NADPH oxidase 2 (NOX2) expression. Bone marrow-derived macrophages (BMDM) isolated from wild-type and nuclear factor E2 related factor 2 (Nrf2) knockout mice were incubated with ASTX without or with LPS. In both unstimulated and LPS-stimulated BMDM, ASTX decreased cellular ROS accumulation regardless of genotype, suggesting that Nrf2 is likely to play a minimal role in the reduction of cellular ROS by ASTX. Taken together, ASTX exerts both anti-inflammatory and antioxidant effects in macrophages, at least in part, by inhibiting NFkB nuclear translocation and by repressing NOX2 expression, respectively. ASTX may be a potential preventive/therapeutic agent for chronic diseases that are caused by chronic inflammation and oxidative stress. (Funded by USDA AFRI 2012-67018-19290)"
Article at:
http://www.fasebj.org/content/29/1_Supplement/603.8.short
From Web MD:
"Astaxanthin is a reddish pigment that belongs to a group of chemicals called carotenoids. It occurs naturally in certain algae and causes the pink or red color in salmon, trout, lobster, shrimp, and other seafood.
Astaxanthin is used for treating Alzheimer's disease, Parkinson's disease, “brain attack” (stroke), high cholesterol, and an eye condition called age-related macular degeneration (AMD). It is also used for preventing cancer.
Astaxanthin is applied directly to the skin for protection against sunburn.
How does it work?
Astaxanthin is an antioxidant. This effect might protect cells from damage. Astaxanthin might also improve the way the immune system functions."
See Web MD for more details:
http://www.webmd.com/vitamins-supplements/ingredientmono-1063-astaxanthin.aspx?activeingredientid=1063&activeingredientname=astaxanthin
Catabasis Pharmaceuticals Invited to Present in a Webinar Hosted by Parent Project Muscular Dystrophy at Pharmaweb.com, on: 08 May 15
Excerpts:
"Catabasis Pharmaceuticals Inc. a clinical-stage drug development company built on a pathway pharmacology technology platform today announced that Joanne Donovan M.D. Ph.D. chief medical officer of Catabasis has been invited by Parent Project Muscular Dystrophy (PPMD) to present on the Company’s upcoming MoveDMD trial. MoveDMD is a Phase 1 / 2 clinical trial of CAT-1004 for the treatment of boys with Duchenne muscular dystrophy (DMD) regardless of dystrophin mutation. The presentation will take place on Wednesday May 13 from 1pm to 2pm ET. The webinar is intended for parents of boys with DMD to describe the MoveDMD trial design and provide enrollment guidance.
The webinar can be accessed by visiting www.readytalk.com and providing the participant code 9449985. The audio dial-in can be accessed by dialing 1.866.740.1260 and providing the access code 9449985.
About CAT-1004
CAT-1004 is an investigational drug that inhibits activated NF-kB a protein that coordinates cellular response to muscular damage stress and inflammation and plays an important role in muscle health. In skeletal muscle activated NF-kB drives muscle degeneration and suppresses muscle regeneration. In animal models of DMD CAT-1004 inhibited activated NF-kB reduced muscle inflammation and degeneration and increased muscle regeneration. In Phase 1 clinical trials in adults CAT-1004 inhibited NF-kB and was well tolerated with no observed safety concerns. Catabasis Pharmaceuticals plans to initiate patient enrollment in a Phase 1 / 2 clinical trial of CAT-1004 the MoveDMD trial for the treatment of DMD in the second quarter of 2015."
Article at:
http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=114663#.VU6pS45VhHw
More: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=114663#.VU6pS45VhHw#ixzz3Zgxwrf7y
Inflammation Seems to Underlie Concussion Symptoms in 'Psych Central', By Traci Pedersen, 9 May 2015
Excerots:
"Inflammation appears to be the underlying factor behind the symptoms of traumatic brain injuries, according to a new study by researchers at McMaster University in Canada.
The findings provide an explanation for why many people with very mild head injuries, or even injuries to other parts of their bodies, still suffer from debilitating post-concussion-like syndromes. These symptoms include headaches, dizziness, cognitive impairment, and other neuropsychiatric symptoms such as irritability, anxiety, and insomnia.
In fact, people who have a very subtle genetic change in a certain inflammatory protein tend to have poorer recovery after brain injury. The findings offer a new look at post-concussion syndrome and settle long-unanswered questions that have been plaguing experts in the field.
It’s inflammation that they have in common,” said Michel Rathbone, M.D., Ph.D., a professor of medicine for McMaster’s Michael G. DeGroote School of Medicine and a lead author of the paper. “Rather than a concussion, we’d like to propose a unifying umbrella term of post-inflammatory brain syndromes or PIBS.”
He added that their new findings will encourage scientists to open up new lines of research into understanding the cause of post-concussion symptoms. So even in a situation where there is no obvious visible brain injury on conventional imaging scans, physicians may be able to still offer treatments that target inflammatory mediators."
Article at:
http://psychcentral.com/news/2015/05/09/inflammation-underlies-concussion-symptoms/84448.html
Study details a link between inflammation and cancer in 'MIT News', Anne Trafton, January 15, 2015
Excerpts:
"Timing of inflammation determines whether potentially cancerous mutations may arise."
"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.
Further studies in the pancreas revealed that inflammation-provoked cell division does not start happening until several days after inflammation begins, while most of the DNA damage occurs right away. This DNA damage is repaired fairly easily without causing potentially cancerous mutations. However, if another bout of inflammation induces DNA damage at a time when cells are dividing due to the previous bout of inflammation, many mutations appear."
"This delay between DNA damage and cell division likely serves as a defense mechanism against mutations from acute bouts of inflammation. However, this defense breaks down when the inflammation occurs soon after the original flare-up or is sustained for a long time.
“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.
The effect in humans could be even more dramatic because many people suffer from chronic inflammation that goes on for years, she 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"
Article at:
http://newsoffice.mit.edu/2015/link-between-inflammation-and-cancer-0115
Common ingredient in packaged food may trigger inflammatory disease in 'AAAS Science', Kelly Servick, 25 February 2015
Excerpts:
"The ingredients that lend a smooth, stable consistency to ice cream, chocolate bars, and other packaged snacks may promote certain chronic inflammatory diseases. That’s the claim of a new study, which finds increases in metabolic disease and intestinal inflammation in mice fed two common emulsifiers used in processed food. The authors are a long way from confirming similar effects in humans, but they suggest that these ingredients cause damage by disrupting the barrier between the immune system and the microbiome—the collection of microbes that inhabit our bodies.
The finding, published online today in Nature, is “believable and remarkable,” says Karen Madsen, a microbiologist at the University of Alberta in Edmonton, Canada, who wasn’t involved in the study. “It sends a really clear message that changes to our food supply are altering our microbiota and our health.”"
"Gut microbes help us fight off infections and resist allergies, but there’s one thing we don’t want them to do: touch our intestinal lining. “Those trillion bugs have kind of got to be kept away from us,” Madsen says. Normally, a layer of mucus separates intestinal cells from gut bacteria. But if bacteria reach these cells, they can stimulate the immune system and cause inflammation. This out-of-control inflammation of the digestive tract is the hallmark of inflammatory bowel disease (IBD), which causes diarrhea, fatigue, and abdominal pain. Chronic inflammation has also been associated with metabolic syndrome—a cluster of co-occurring conditions, including obesity and high blood pressure, that increase a person’s risk of heart disease and diabetes.
Benoit Chassaing, a microbiologist at Georgia State University in Atlanta, wondered if such a bacterial invasion could explain what he describes as a “perfect correlation” between the increasing use of food additives in industrialized countries and the incidence of IBD. (The disease affects more than a million people in the United States and appears to be on the rise.) Work by other groups led Chassaing and colleagues to focus on emulsifiers—detergentlike compounds that coax into a smooth, creamy mixture ingredients that might otherwise prefer to separate, like the milk fat and water in ice cream. A 2009 study found that feeding the emulsifier carboxymethylcellulose (CMC) to genetically engineered mice that were already predisposed to intestinal inflammation led to excess growth of bacteria in their small intestines and increased inflammation."
Article at:
http://news.sciencemag.org/biology/2015/02/common-ingredient-packaged-food-may-trigger-inflammatory-disease
Weill Cornell Investigators Discover a New Pathway that Prevents Chronic Inflammation in the Gut at Weill Cornell College website, April 23, 2015)
Excerpts;
NVESTIGATORS SHOW HOW IMMUNE CELLS ARE "EDUCATED" NOT TO ATTACK BENEFICIAL BACTERIA
An international research team led by Weill Cornell Medical College investigators has discovered an answer to why the human immune system ignores roughly 100 trillion beneficial bacteria that populate the gastrointestinal tract. The findings, published April 23 in the journal Science, advance investigators' understanding of how humans maintain a healthy gastrointestinal tract, and may provoke new ways to treat inflammatory bowel disease — including Crohn's disease and ulcerative colitis — whose origins have been mysterious and treatment difficult.
The investigators studied T cells — critical components of the adaptive immune system — which have the capacity to recognize, eliminate and remember foreign microbes that invade our bodies. T cells are named after the thymus, an organ where they develop and are taught not to attack normal human tissues and organs, leaving them free to target and eradicate disease-causing foreign invaders. One question that had puzzled scientists until now is how these cells learn to ignore beneficial bacteria in the intestine that are also foreign, but not harmful.
In the study, the research team discovered that once they leave the thymus, T cells are again educated in the gastrointestinal tract, or gut, to leave beneficial bacteria alone. This dual education strategy is vital to supporting healthy immune function, the investigators say. Disruption in the pathway that facilitates this education, they add, causes the immune system to attack beneficial bacteria in the intestine, which is often linked to the development and progression of diseases like inflammatory bowel disease, HIV, viral hepatitis, cardiovascular disease, obesity, diabetes and cancer. Therapeutic strategies to promote and boost the activity of this education pathway may be beneficial in treating patients with these chronic inflammatory disorders, the investigators say."
Article at:
http://weill.cornell.edu/news/pr/2015/04/weill-cornell-investigators-discover-a-new-pathway-that-prevents-chronic-inflammation-in-the-gut.html
Researchers Reveal Cellular Mechanism Behind Cancer in Chronic Inflammatory Diseases in 'Imuno-Oncology News', FEBRUARY 16TH, 2015
Excerpts:
"A recent study led by researchers at The Wistar Institute revealed for the first time the cellular mechanism underlying cancer development induced by chronic inflammatory diseases. The study, entitled “Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells,” was published in the Journal of Experimental Medicine.
Inflammation is known to be an essential and natural mechanism by which the body recovers from injury and disease. Chronic inflammation, however, has been directly linked with different types of cancer, although the reasons underlying this association at the cellular level are not clear.
“While we know that cancer is initiated because of genetic alterations, we also know that cancer’s development relies heavily on environmental factors,” said the study’s senior author Dr. Dmitry Gabrilovich in a news release. “Inflammatory conditions are closely linked to cancer, yet it’s a very complex process, making it difficult to determine how certain components contribute to the development of cancer.”
Researchers have now identified a complex mechanism underlying the development of these types of cancer. They found that inflammatory conditions are linked to specific myeloid cells named immature granulocytic cells. "
Article at:
http://immuno-oncologynews.com/2015/02/16/researchers-reveal-cellular-mechanism-behind-cancer-chronic-inflammatory-diseases/
Chronic Inflammation May Drive Colon Cancer in 'Colon Cancer News Today', February 16, 2015
Excerpts:
"In a recent study entitled “Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells,” a research team identified that a specific type of immune cell, immature myeloid cells, are the first step towards the development of chronic inflammation-associated tumors, such as colon cancer. The study was published in the Journal of Experimental Medicine.
Inflammation is a protective immunovascular response that is activated upon harmful stimuli, such as pathogens, toxic compounds or even damaged tissues. However, while inflammation is a crucial response of the body’s defense, chronic inflammation, i.e., a persistent, unresolved inflammation, is known to contribute to cancer development such as colon cancer, basal cell carcinoma, lung, liver, among others. However, as inflammation is a complex process, the role of specific cells, mainly myeloid cells, linking inflammation to cancer remains largely unknown.
Here, a research team led by Dmitry Gabrilovich, M.D., Ph.D., at The Wistar Institute in Philadelphia discovered that a specific type of myeloid cells, granulocytic immature myeloid cells (IMCs), accumulate in inflammatory conditions that lead to the development of tumors, as those in the skin and colon."
"Furthermore, researchers identified that the molecular switches governing this process includes the CCL4 chemokine, released by granulocytic IMCs cells and responsible for the attraction of T cells, which in turn produce a proinflammatory cytokine, interleukin-17 (IL-17), a player already established as playing a role in tumor development."
Article at:
http://coloncancernewstoday.com/2015/02/16/chronic-inflammation-may-drive-colon-cancer/
?Anatabine reduces AB-40 and AB-42---(R,S)-Anatabine in Cayman Chemicals website
Excerpt:
"R,S)-Anatabine is a minor alkaloid produced in plants of the Solanaceae family, including tobacco.1 The detection of ?(R,S)-anatabine in urine is used as an indicator of tobacco use, particularly when nicotine-containing products (gum, patches, inhalers, and medications) are also being used.2,3 ?(R,S)-Anatabine increases nicotine self-administration and locomotor activity in rats.4 Of note, ?(R,S)-anatabine diminishes amyloid beta (Aß) production in vitro and in vivo. ?(R,S)-Anatabine reduces (600 µg/ml) the transcription and protein levels of ß-secretase, lowering the amount of Aß1-40 and Aß1-42 in a dose dependent manner in SHSY-5Y cells. ?(R,S)-Anatabine also dose dependently inhibits NF-?B activation.5"
Article at:
https://www.caymanchem.com/app/template/Product.vm/catalog/11001/promo/emolecules