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Bob McDonnell Sentenced To Prison in Huffington Post, 01/06/2015, Ryan J. Reilly
Excerpt:
"Former Virginia Gov. Bob McDonnell, who was once on the short list of potential Republican vice presidential nominees, was sentenced to two years in prison by a federal judge on Tuesday."
Article at:
http://www.huffingtonpost.com/2015/01/06/bob-mcdonnell_n_6419708.html?ir=Politics&utm_campaign=010615&utm_medium=email&utm_source=Alert-politics&utm_content=FullStory
Jonnie Williams' Next Idea? in Tobacco Industry Today, Central figure of the McDonnell trial reportedly has a new business plan for nicotine derivative., 4 January, 2015, PETER GALUSZKA
Article:
"Is business huckster Jonnie R. Williams Sr. trying to cash in on the e-cigarette, “vaping” craze?
It could be, according to The Washington Post. In a lengthy story today about convicted former Gov. Robert F. McDonnell due for sentencing Tuesday, the Post reports that two people who know Williams say he is exploring a new business venture -– “anatabine-filled e-cigarettes.”
Few other details are available but it many ways, it makes perfect sense. Williams, the glib-talking former head of Star Scientific and self-taught scientist, has for years tried to come up with products that tap the good aspects of nicotine without the bad.
On was CigRx, a smoking cessation treatment, and Antabaloc, the dietary supplement and anti-inflammatory that got McDonnell and his wife, Maureen, in so much trouble.
Williams, who was the star witness for the prosecution in the six-week-long corruption trial of the McDonnell last summer, has since left Star Scientific, the firm he founded that made Antabaloc and CigRx, and is living in Florida, the Post reports. Williams gave the McDonnells more than $177,000 in loans and gifts in exchange for help pushing his products.
Rock Creek Pharmaceuticals, which assumed the name of Star Scientific last year, pulled both CigRx and Antabaloc off the shelves in deference to complaints by the U.S. Food and Drug Administration. They are no longer sold.
Anatabine is derived from nicotine and was a key ingredient in Anatabloc. In electronic cigarettes, which are “vaped” with water, nicotine is absorbed in the body in water vapor and provides a “kick” and pleasing feeling that one gets smoking a traditional tobacco cigarette. One difference is that an e-cigarette has none of the carcinogenic tar and other products that are harmful to health.
Since anatabine is similar to nicotine, one imagines it could be used as a substitute. Williams is no stranger to tobacco. His relatives worked for a larger tobacco company and Williams at one time ran an operation that made discount cigarettes and Swisher Sweet cigars. He is a strong believer that nicotine as enormous potential as a healing substance.
The market for e-cigarettes, meanwhile has expanded tremendously in recent years. Proponents believe vaping offers the good aspects of smoking tobacco with few of the bad while critics question the safety of having pure nicotine in small e-cig containers."
Article at:
http://tobacco.einnews.com/article/242663663/CkBYfd0_2lJc6_xg
I think RCPI can also 'fastrak' if they apply for it. GliaCure's drug seems bio-similar in application so if they can fastrak, RCPI should also have a shot. No drug yet has cured Alzheimers. I have no idea who will win or if there will be more than one winner. I post these to indicate what is happening around the 'chronic inflammation' arena and what others are doing.(the competition) RCPI has a good shot if all turns out well with their clinical trials. I have more confidence in RCPI than others because they did have some 'human' trials with negligible side effects. My reading is even some big name pharmaceuticals who have dominated this market have failures up the phase 3 where the efficacy targets/issues are to be demonstrated. Many large pharmas buyout/license drugs from small bio firms after they see confidence that the preliminary human trials show some success. Maybe that is what Mullan is trying to do with the tissue analysis in phase 1 that normally covers only dosage/safety issues. This may be his leg up in this race. None of us have any idea of the effective dosage levels except from the user guesses with Anatabloc (most of us) for a particular application. Most small bio firms lose money during the research phase and don't hit financial solvency until and if their drug hits big with the medical community with successful efficacy ratings.We longs, are betting Mullan will hit a home-run when anatabine citrate applications are better understood with some clinical trials under his belt. I wouldn't be surprised if Mullan is already experimenting with a 'cocktail' and hybrids thereof. Again, that's my guess---others are entitled to their guess also, both postive and negative.
GliaCure raises $5.8 million for Alzheimer’s drug that treats the glial cells in MedCity News, August 4, 2014 12:24 pm by Meghana Keshavan
Article:
"Boston-based GliaCure is taking a slightly different approach to treating Alzheimer’s disease – instead of targeting the neurons, its drug compound focuses on glial cells – a cell type that’s generally overlooked in drug development.
It has raised a $5.8 million oversubscribed Series B round, exceeding its initial goal of $5 million. The funding comes from a network of private investors and high net worth individuals. The company, founded in 2011, closed its $2.75 million Series A in 2012.
The company’s lead product, GC021109, is a small molecule drug that works in two ways – it stimulates phagocytosis and reduces pro-inflammatory cytokines.
It’s slated to enter clinical trials for its Alzheimer’s target in the third quarter of this year. The company is finding that the phagocytic and anti-inflammatory properties of the drug could help treat other conditions, including psoriasis, Parkinson’s disease, multiple sclerosis and glaucoma.
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GliaCure has licensed this lead compound exclusively from Tufts University; however, it has several other programs under development. For instance, it has a therapeutic line with astrocytic targets related to sleep disorders and depression, the company said.
The company is led by Philip Haydon, the chair of neuroscience at Tufts University. GliaCure’s site outlines the case for choosing glial cells as a target quite nicely:
The brain is composed of two cell types: the much-studied and electrically active neurons and glia, a second cell type that is electrically inactive. For many years work in the neurosciences focused exclusively on neurons; glia were left largely unstudied until a seminal discovery made by Philip Haydon in the early 1990’s. This work, demonstrating that glia are active signaling components of the brain, was published in the journal Nature in 1994.
For the past 19 years, Philip Haydon’s laboratory has focused on the study of glia with a goal of understanding the importance of these cell types in the control of brain function in health and disease. From this a range of disease areas has been identified as having potential for new therapy development. These disorders include Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, Down’s syndrome, glioblastoma, pain and neuropathic pain, epilepsy, and such debilitating and widespread psychiatric disorders as depression, schizophrenia and disorders of sleep.
Exciting new research in Philip Haydon’s laboratory at Tufts University School of Medicine has identified a novel target for the development of therapeutics for the treatment of Alzheimer’s. This target is known to stimulate phagocytosis by glia. Target activation reduces amyloid plaque burden, restores plasticity in the brain and restores learning and memory."
Article at:
http://medcitynews.com/2014/08/gliacure-raises-5-8-million-alzheimers-drug-treats-glial-cells/
GliaCure’s Lead Product, GC021109, Receives FDA Fast Track Designation
GLIACURE’S LEAD PRODUCT, GC021109, RECEIVES FDA FAST TRACK DESIGNATION in Gliacare website
Announcement:
"GliaCure’s lead product candidate for Alzheimer’s disease, GC021109, has been awarded Fast Track status by the FDA. Biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. The Fast Track designation facilitates more frequent meetings with the FDA to discuss all aspects of development and allows submission of a new drug application on a rolling basis as data become available.
GliaCure board member Joseph Zakrzewski said, “Being awarded Fast Track status for GC021109 is a major achievement for the company. This designation for GC021109 by the FDA is a recognition of the significant unmet medical need for patients with Alzheimer’s disease and the potential our approach offers for these patients.”
As reported previously, a first-in-human Phase 1a study of GC021109 began on September 22, 2014. GliaCure is currently planning its Phase 1b trial, a multiple ascending dose study in mild-to-moderate Alzheimer’s patients."
Announcement at:
http://gliacure.com/gliacures-lead-product-gc021109-receives-fda-fast-track-designation/
GliaCure Enters First-in-Human Clinical Trial in Alzheimer's Disease in PR Newswire, Sept. 25, 2014
News Release:
"BOSTON, Sept. 25, 2014 /PRNewswire/ -- GliaCure, a privately-held biotechnology company focused on the development of novel therapies for neurological and neuropsychiatric disorders based on glial targets, announced today that has initiated dosing of healthy volunteers in a first-in-human Phase 1a clinical trial of its lead product candidate, GC021109, a novel compound developed as a disease-modifying treatment for Alzheimer's disease. In pre-clinical animal studies GC021109 has demonstrated a unique, dual mechanism: it both reduces inflammation and reduces amyloid beta, two important factors in the etiology of Alzheimer's disease. These studies of GC021109 also suggest that it is highly orally bioavailable and has a broad therapeutic window.
"Since its inception GliaCure has pursued an aggressive development timeline yet aimed to be very cost effective, so we are exceptionally pleased that we have been able to move from compound development to first-in-human dosing in less than three years," said GliaCure President Phil Haydon. "Much of the credit for reaching this milestone has to go to our consultant development team and to our committed investors. Together, they have offered us the resources and expertise to make fast, well thought out decisions to develop a robust study."
GliaCure's Phase 1a trial of GC021109 began on September 22. The trial is a randomized, double-blind, placebo-controlled, study of single ascending doses in healthy subjects and is intended to determine the safety, tolerability, and pharmacokinetics of GC021109. GliaCure is currently planning its Phase 1b trial, a multiple ascending dose study in mild-to-moderate Alzheimer's patients.
About GliaCure, Inc.
GliaCure is a privately held company that is pioneering the development of novel therapeutics aimed at treating neurological and neuropsychiatric disorders of the brain. The company's approaches are based on glial targets, a cell type in the brain that has previously been largely overlooked in drug discovery. GliaCure's lead product candidate, GC021109, is a small molecule that in preclinical studies has demonstrated two primary actions downstream of target engagement: the stimulation of phagocytosis and anti-inflammatory actions in which levels of pro-inflammatory cytokines are reduced. GC021109 is currently being developed primarily as a disease modifying treatment for Alzheimer's disease and commenced a Phase 1a clinical trial for the disorder in Q3 2014. The dual phagocytic and anti-inflammatory actions of GC021109 have the potential to affect other disorders, including psoriasis, Parkinson's disease, and multiple sclerosis. GliaCure has an exclusive license to the GC021109 compound and related technology from Tufts University. GliaCure also has a pipeline program for the development of therapeutics for astrocytic targets related to sleep disorders and depression. The company is based in Boston and is led by Professor Philip G. Haydon, who also holds the position of Chair of Neuroscience at Tufts University.
CONTACT: Yolande Haydon, 610-246-6012, yolande.haydon@gliacure.com
SOURCE GliaCure, Inc.
News Release at:
http://www.prnewswire.com/news-releases/gliacure-enters-first-in-human-clinical-trial-in-alzheimers-disease-277105411.html
Creative Minds: REST-ling with Alzheimer’s Disease in National Institutes of Health, March 25, 2014 by Dr. Francis Collins
Article:
"Why do some people remain mentally sharp over their entire lifetimes, while others develop devastating neurodegenerative diseases that destroy their minds and rob them of their memories? What factors protect the human brain as it ages? And can what we learn about those factors enable us to find ways of helping the millions of people at risk for Alzheimer’s disease and other forms of senile dementia?
Those are just a few of the tough questions that Bruce Yankner, a 2010 recipient of the NIH Director’s Pioneer Award, has set out to answer by monitoring how gene activity in the brain’s prefrontal cortex (PFC) changes as we age. The PFC is the region of the brain involved in decision-making, abstract thinking, working memory, and many other higher cognitive functions; it is also among the regions hardest hit by Alzheimer’s disease.
A professor of genetics and neurology at Harvard Medical School in Boston, Yankner’s initial work uncovered age-specific changes in activity of certain genes associated with learning and memory [1]. A computational analysis suggested that a master regulator protein, with the awkward name repressor element 1 silencing transcription factor (you can understand why scientists just call this “REST”), may be controlling these genes in older brains. This discovery was surprising, because while REST was known to be active during early fetal development, it was thought that REST was turned off for the rest of a person’s life.
Now, in a new study published in Nature, Yankner has found evidence suggesting that the gene that codes for the REST protein switches on again as our brains age [2]. In this biological “second act,” REST plays a role in the activation of an anti-stress response that protects aging brain cells from destructive molecules called free radicals and toxic misfolded proteins, such as amyloid, that cause them to degenerate and die.
In their latest work, Yankner and his colleagues compared the levels of REST in a type of brain cell, called a neuron, in the PFCs of young adults (20–35 years) and healthy elderly adults (73–106 years) without Alzheimer’s disease. They found that REST was present at low levels in the PFC neurons of young adults, but rose steadily with age. Further examination revealed that REST switches off genes that trigger cell death, along with other genes that have been implicated in Alzheimer’s disease.
The researchers went on to look at REST activity in the PFC neurons of people with Alzheimer’s disease: some with early and others with late stage disease. It turns out that if a person showed any signs of Alzheimer’s disease, REST was almost absent from the control center—the nucleus—of these brain cells. Somehow, REST was evicted from the nucleus and exiled to the cell’s “dumpsters,” where, along with toxic misfolded proteins, it was destroyed. Similar changes were also seen in the PFC neurons of people suffering from other forms of degenerative brain disease, including conditions such as frontotemporal dementia and dementia with Lewy bodies.
These findings suggest REST may provide a clue to the puzzle of why some older people whose brains contain what’s long been considered the hallmark of Alzheimer’s disease—amyloid plaques—do not develop the disorder. To investigate this further, Yankner’s team tapped into the wealth of clinical information and tissue carefully gathered by the NIH-funded Religious Orders Study, a prospective, long-term human study begun in 1993. In this study, more than 1,000 older members of various Catholic communities have volunteered to undergo annual assessments of their memory and other cognitive skills while they are alive, and, upon their deaths, to donate their brains to research. Yankner and his colleagues focused on the subset of volunteers who had retained strong memory skills until their deaths, despite having brains that showed classic signs of Alzheimer’s disease. The researchers’ analysis found that these individuals’ neurons contained significantly higher levels of REST than did those of their counterparts who had suffered from dementia.
In addition to human studies, Yankner’s team explored the function of REST in various model systems, including worms, mice, and brain cells grown in laboratory dishes. Their work showed that when they lowered the activity of the equivalent of the REST gene in the roundworm Caenorhabditis elegans, the microscopic worms were more sensitive to the damaging effects of free radicals and amyloid protein. When the REST gene was added back in, the worms were protected.
Next, the researchers knocked out the REST gene in the brains of mice—a move aimed at mimicking the situation in humans with Alzheimer’s disease. When the REST-deficient mice were young, their neurons appeared to be alive and well. However, as these mice grew older, a significant number of neurons died and degeneration set in. In addition, when the investigators removed neurons from the REST-deficient mice and grew them in a lab dish, the brain cells were far more likely to die when exposed to toxic agents, such as free radicals, than those from normal mice. Encouragingly, when researchers inserted the REST gene back into the deficient neurons, they recovered and became more resistant to toxic agents.
There are important implications from this groundbreaking work. First, these lab results suggest that REST may be necessary to keep aging brain cells alive and well. Furthermore, these data suggest that it might be possible to develop ways to restore protective levels of REST, thereby preventing, halting, or maybe even reversing the damage done to neurons in Alzheimer’s disease.
Yankner’s team is now beginning to search for molecules that safely boost REST levels in brain cells. Intriguingly, lithium, which is currently used as a treatment for bipolar illness, raised levels of REST and increased its function in brain cells grown in the laboratory. However, it will take considerably more research to figure out whether this could be a safe and effective treatment for Alzheimer’s disease, or whether other drugs that target the REST pathway might be promising.
Intriguingly, Yankner’s group happened to detect the very highest levels of REST in the brains of people who lived to an extremely old age, such as centenarians. They’ve also discovered that REST stimulates genes that are known to increase lifespan in animal models. So, as you might imagine, this group of REST researchers won’t be resting anytime soon! In addition to all of their work on Alzheimer’s disease, they are now keen to explore whether this protein might play an even broader role in healthy aging."
Article at:
http://directorsblog.nih.gov/2014/03/25/creative-minds-rest-ling-with-alzheimers-disease/
REST and stress resistance in ageing and Alzheimer’s disease in Nature International Journal of Science, March 204,
Tao Lu, Liviu Aron, Joseph Zullo, Ying Pan, Haeyoung Kim, Yiwen Chen, Tun-Hsiang Yang, Hyun-Min Kim, Derek Drake, X. Shirley Liu, David A. Bennett, Monica P. Colaiácovo & Bruce A. Yankner
Abstract:
"Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer’s disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer’s disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid ß-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid ß-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer’s disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain."
Article at:
http://www.nature.com/nature/journal/v507/n7493/abs/nature13163.html
Proteins Can Help Treat Alzheimer’s Discovered By Scientists in Capital Wide, January 3, 2015 by Gilles Legault
Article:
"Making of the protein is one of the most important functions that any cell has to do, well the good thing is that now scientist have said that the proteins can help treat the condition of the Alzheimer’s. As some proteins do not require any DNA to produce more proteins so they can actually help in this matter, due to this there is an odd behavior of the Rqc2 which can be utilized as the unit to control the activity of the cells. This result in treating the Alzheimer’s or Huntington’s diseases, with the passage of time it can surely treat other conditions too.
But in people with Alzheimer’s and other dementias, the protein was sharply depleted in key brain regions.
‘Our work raises the possibility that the abnormal protein aggregates associated with Alzheimer’s and other neurodegenerative diseases may not be sufficient to cause dementia; you may also need a failure of the brain’s stress response system,’ said Bruce Yankner, Harvard Medical School professor of genetics and leader of the study.
‘If true, this opens up a new area in terms of treatment possibilities for the more than five million Americans currently living with Alzheimer’s disease,’ said Yankner, who in the 1990s was the first to demonstrate the toxic effects of amyloid beta, the hallmark abnormal protein in Alzheimer’s.
The research underscores a different way of looking at neurodegenerative diseases.
Instead of focusing on the negative changes that cause disease, researchers examined trouble spots in the brain’s ability to protect itself over time.
Yankner said the study suggests a person may be able to resist the toxic effects of Alzheimer’s if REST levels remain high.
‘If we could activate this stress-resistance gene network with drugs, it might be possible to intervene in the disease quite early,’ he said.
But they cautioned that much more needed to be determined, including whether the decline of REST was a cause, or an effect, of brain deterioration, and whether it was specific enough to neurological diseases that it could lead to effective therapies.
He also has thoughts about a potential treatment, lithium, which he said appears to stimulate REST function, and is considered relatively safe.
As dementia rates rise, researchers believe preventive studies such as this will be critical in finding a cure. Some estimates say the number of people living with dementia will double to nearly 70 million by 2030.
‘This is an extremely important study,’ said Li-Huei Tsai, director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, who was not involved in the research but wrote a commentary accompanying the study.
‘This is the first study that is really starting to provide a plausible pathway to explain why some people are more vulnerable to Alzheimer’s than other people.’
Article at:
http://www.thecapitalwide.com/2509/proteins-can-help-treat-alzheimers-discovered-by-scientists/
Interesting forum/blogs on longetivity can be found at:
http://www.longecity.org/forum/page/index2.html/_/feature/about-r28
Some interesting views and data are supplied in a constructive atmosphere. Follow what interests you and participate if you have a kin to do so.
NF-Kappa B Forum: NF-kappaB, a critical key to life extension?
Interesting discussion regarding NF-kappaB at:
http://www.longecity.org/forum/topic/25261-nf-kappab-a-critical-key-to-life-extension/
Centenarians in longerhealthylife.net,
Article:
"Starting closer to us, human centenarians (living over 100 years) have been studied to determine what characteristic biologic factor(s) leads to long life. These people are a very widely varying group. Diets of these centenarians have considerable variation with no food outstanding as a common source of their longevity. Some smoke, some drink, some are good tempered, and some are mean as nails. Cholesterol levels vary considerably. The oldest ever recorded (well documented) was Jean Calumet of France who died at 122 years of age. She smoked and drank all of her life until about 100 years of age. She claimed that chocolate had kept her alive so long. We can set the maximum human life span by this 122 years of age, as we have no other documented examples of greater human life span.
The only common finding shared by all centenarians(besides being from relatively long lived families is 1.) a very well preserved insulin response to rising dietary incoming blood sugar with a rather Low Body Mass Index (=weight divided by (height)^2 in kilogram/meter system-meaning that they were relatively slim) AND 2.) a much lower rate of chronic inflammatory activation with age .
You can calculate your own BMI at the NHBL site. Notice that too high a value and too low a value are both considered less healthful.
This absence of age adjusted higher levels of resistance to insulin and lower chronic inflammation levels in centenarians is critical.
This better handling of glucose compares to the far more common finding of a continual rise in insulin resistance with rising fasting insulin levels and some rise in fasting blood glucose levels in normal middle aged humans. Insulin sensitivity and insulin resistance are both focused on the ability to handle an increased level of glucose entering the blood stream from meal with low insulin levels (low insulin resistance = high Insulin sensitivity). Conversely, very high blood circulating insulin levels are harmful. High insulin resistance in response to rising blood sugar means that cells are not as sensitive to low level of insulin to absorb the blood sugar. This forces the body to produce and release into the blood stream much more insulin. Insulin resistance means the body does not efficiently remove glucose from the blood stream. Higher blood stream levels of glucose damage proteins by complex free radial mechanisms. AIn addition to better control over glucose by low levels of insulin, centenarians also have lower levels of blood circulating triglycerides (triglycerides are are the typical fats and oils we buy in the market). Centenarian's levels of insulin and triglyceride have risen over life, just like other people, but not as much as others. Notable among centenarians is the post mortem finding of virtually no evidence of Alzheimer's disease or similar dementia manifestations ( http://www.allbusiness.com/professional-scientific/scientific-research/258199-1.html ).
What researchers are finding from these major centenarian studies is that there is hardly anything in common among these people. They have high cholesterol and low cholesterol, some exercise and some don't, some smoke, some don't. Some are nasty as can be, some nice and calm and some are ornery... But, they all have relatively low sugar for their age, and they all have low triglycerides for their age... And, they all have relatively low insulin... If there is a single marker for lifespan, as they are finding in the centenarian studies, it is insulin, specifically insulin sensitivity. Low Grain and Carbohydrate Diets Treat Hypoglycemia, Heart Disease, Diabetes Cancer and Nearly ALL Chronic Illness Joseph Brasco, MD
In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action." Glucose tolerance and insulin action in healthy centenarians G. Paolisso, A. Gambardella, S. Ammendola, A. D'Amore, V. Balbi, M. Varricchio and F. D'Onofrio Am J Physiol. 1996 May;270(5 Pt 1):E890-4
...studies comparing adults of various ages with centenarians on various aspects of body composition and insulin action found that centenarians had a lower body mass index, lower levels of body fat, lower plasma triglycerides, and lower indicators of oxidative stress(Barbieri et al. 2003;Paolisso et al. 1997). Centenarians also had a higher insulin sensitivity than that of much younger adults (i.e., their insulin resistance was much lower). Although the centenarians had low absolute levels of insulin like growth factors (IGF-1), their levels of active IGF-1 (i.e. not bound to a transport protein) was higher than that of aged adults (75-99 yrs) but lower that that of younger adults < < 50 yrs). Thus, the possibility exists that these centenarians have somehow preserved their IGF-1 and insulin sensitivity. The Biology of Aging (1998) Robert Arking
The way to treat virtually all of the so-called chronic diseases of aging is to treat insulin itself... Insulin resistance is the basis of all of the chronic diseases of aging, because the disease itself is actually aging. Insulin and Its Metabolic Effects Ron Rosedale, M.D.
The gradual age-related decline in physiologic function and the late life exponential rise of a diverse group of age-associated diseases are explained by imbalance in specific hormonal axes and cumulative growth factor exposure, respectively. Nutritionally driven 'normal' insulin exposure is central to both cumulative growth factor exposure and imbalance of the insulin-growth hormone axis. Halving normal young adult insulin levels by increased insulin sensitivity may slow the aging process. Insulin exposure controls the rate of mammalian aging. Parr, Tyler Mech Ageing Dev. 1996 Jul 5;88(1-2):75-82.
The present nationwide census-based study of Japanese centenarians found that 10.4% centenarians were autonomous centenarians, in other words, had preserved ADL, cognitive status, and psychosocial status. In this study, such centenarians were considered to be models of successful aging.http://onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2006.01019.x/full
The Japanese Centenarian Study: Autonomy Was Associated with Health Practices as Well as Physical Status
1. Akiko Ozaki RN, PhD1, Makoto Uchiyama MD, PhD2, Hirokuni Tagaya MD, PhD4, Takashi Ohida MD, PhD3, Ryuji Ogihara MD, PhD5
Article first published online: 12 DEC 2006 J Amer Geriat Soc Volume 55, Issue 1, pages 95–101, January 2007
While most centenarians show various levels of age associated diseases, some CENTENARIAN humans show no known diseases of age that are common in much younger humans. Now we are beginning to realize that we are PREMATURELY dying by an INFLAMMATION driven age-associated diseases is not necessary.
This also applies to the high fat (modest or minor to major obesity) driven insulin insensitivity (typically type 2 diabetes) that generates elevated inflammatory levels that then further worsens the type 2 diabetes in to an ever worsening condition while also accelerating the dev elopement of all the other age-associated diseases. What is AMAZING is that it does not take much increase in "inside the belly fat" to begin this process, then it amplifies on its OWN ! This is not "NORMAL AGING", but it is the commonplace in all animals who can eat as much as they want. This was never factored into evolution because wild animals are almost never obese unless they live in extremely cold climates where this is a survival necessity. The food bounty of civilization that is enjoyed by humans and domesticated animals is almost unheard of in wild nature. Nature is much more cyclic abundance and dearth of nutrition. Under the lucky unusual conditions when abundant food was present for the life of a wild animal (say early colonizers of a food rich, competition low environment), the animals offspring would have a shorter life span by epigenetic changes as we have examined in the ORIENTATION section table of article blurbs"
Article at:
http://longerhealthylife.net/SUBS%20(Read%20More...)/Centenarians.html
Read More About Medicines in Development for Alzheimer's Disease in Pharma
Excerpt:
"America’s biopharmaceutical research companies are investigating or developing 93 medicines to help the more than five million patients in the United States who are living with Alzheimer’s. The medicines in development – all in either clinical trials or under review by the Food and Drug Administration – include 81 for Alzheimer’s, 11 for cognition disorders and 2 for dementias, according to a new report released by the Pharmaceutical Research and Manufacturers of America (PhRMA)."
Article at:
http://www.phrma.org/research/medicines-development-alzheimers-disease
'First Baby Step' Toward Anti-Aging Drug in Web MD, Dennis Thompson,Dec. 24, 2014
Excerpt:
" Those who received the experimental version of rapamycin developed about 20 percent more antibodies in response to the flu vaccine, researchers found. Even low doses of the medication produced an improved immune response.
The researchers also found that the group given the drug generally had fewer white blood cells associated with age-related immune decline.
Mannick called this study the "first baby step," and was reluctant to say whether it could lead to immune-boosting medications for the elderly.
"It's very important to point out that the risk/benefit of MTOR inhibitors should be established in clinical trials before anybody thinks this could be used to treat aging-related conditions," she said.
Barzilai was more enthusiastic. Research such as this could revolutionize the way age-related illnesses are treated, he said.
"Aging is the major risk factor for the killers we're afraid of," he said, noting that people's risk for heart disease, cancer and other deadly illnesses increases as they grow older. "If the aging is the major risk, the way to extend people's lives and improve their health is to delay aging."
Until science focuses on aging itself, "you're just exchanging one disease for another," Barzilai said. For example, he said, a person receiving cholesterol-lowering treatment to prevent heart disease likely will instead fall prey to cancer or Alzheimer's disease."
Article at:
http://www.webmd.com/healthy-aging/news/20141224/researchers-take-first-baby-step-toward-anti-aging-drug
Mouse study finds immune system could promote hair growth in Medical News Today, James McIntosh, 24 December 2014
Excerpt:
"Perez-Moreno made an initial discovery while conducting a separate study on mice. She noticed that the mice she was working with for that project started to grow new hair after receiving anti-inflammatory drugs."
""This line of research should facilitate the development of novel therapeutic strategies for the manipulation of undesired human hair loss or growth that target perifollicular immunocytes, such as macrophages.""
Article at:
http://www.medicalnewstoday.com/articles/287367.php
CTA 14 day approval for trials to begin. See following link for details:
http://www.ct-toolkit.ac.uk/routemap/cta-submission
You can go forward or backwards from this page to see the entire process. Assuming RCPI is at the CTA stage, this is where they appear to be.
The 'routemap' or flow diagram is here:
http://www.ct-toolkit.ac.uk/routemap
It is possible that this may have changed since it is dated 2004, 10 years ago.
European Clinical Trials Authorization (CTA):
Clinical trial authorisation framework in Europe - overview
Dr Chantal Bélorgey, Head, CTs Department, Afssaps, France
Chair of CTFG, EMA – SME meeting 28 May 2010
Authorization looks like as early as 60 to as late as 90 days.
PDF document at:
http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2010/06/WC500093373.pdf
A Clinical Trial of Progesterone for Severe Traumatic Brain Injury in The New England Journal of Medicine, December 2014
Brett E. Skolnick, Ph.D., Andrew I. Maas, M.D., Ph.D., Raj K. Narayan, M.D., Roland Gerritsen van der Hoop, M.D., Ph.D., Thomas MacAllister, Ph.D., John D. Ward, M.D., Neta R. Nelson, M.P.H., and Nino Stocchetti, M.D. for the SYNAPSE Trial Investigators
Article:
"BACKGROUND
Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. We investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized clinical trial.
METHODS
We conducted a multinational placebo-controlled trial, in which 1195 patients, 16 to 70 years of age, with severe TBI (Glasgow Coma Scale score, =8 [on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness] and at least one reactive pupil) were randomly assigned to receive progesterone or placebo. Dosing began within 8 hours after injury and continued for 120 hours. The primary efficacy end point was the Glasgow Outcome Scale score at 6 months after the injury.
RESULTS
Proportional-odds analysis with covariate adjustment showed no treatment effect of progesterone as compared with placebo (odds ratio, 0.96; confidence interval, 0.77 to 1.18). The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo.
CONCLUSIONS
Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials. (Funded by BHR Pharma; SYNAPSE ClinicalTrials.gov number, NCT01143064.)
Article at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1411090?query=TOC
Delayed Aging Is the Ultimate Preventative Medicine in Patrick Cox's Transformational Technologies, October 2014
Excerpts:
"A new paper in the journal Health Affairs makes the point that preventing the cause of disease is better than trying to cure diseases. The title is “Substantial Health and Economic Returns from Delayed Aging May Warrant a New Focus for Medical Research” and the abstract is online here'
"While many scientists are interested in the underlying cause of most diseases, which is aging, our legal and regulatory system is so biased against modification of the aging process, it isn’t even recognized as a legitimate therapeutic target. If you had a compound that helped delay aging by maintaining a state of health for five or ten years, you couldn’t get it approved as a drug. In fact, an investigational new drug (IND) application to the Food and Drug Administration would be rejected because aging is not recognized as a medical problem.
In fact, aging is “THE” medical problem. With the exception of a relatively few genetic disorders and communicable diseases, all diseases are directly correlated to aging. As our biological systems get older, they lose functionality. Eventually, this lack of functionality cascades into all the major killers. We’re talking about cardiovascular disease, cancers, Alzheimer’s, type 2 diabetes, arthritis, hypertension, COPD, and even depression and obesity-related conditions. From a policy perspective, these diseases are the major drivers of federal debt and deficit."
"Chronic Inflammation
Chronic inflammation, dubbed inflammaging by gerontologist Claudio Franceschi, is actually a form of autoimmune disorder. Three scientists won the 2011 Nobel prize in medicine for their work explaining how our innate immune systems, which protect us when we’re young, can shorten our lives.
A major player in this process is the immune system’s alarm, nuclear factor kappa B (NF-kB). When we are young, NF-kB activates an immune response when we are injured or infected, then promptly turns off when it’s no longer needed. For various reasons, NF-kB increasingly activates as we age, apparently interpreting the effects of aging as injury, and never really shuts down. Cytokines and other immune system weapons are turned against us, leading to a wide variety of inflammation-related diseases."
"The Albert Einstein College of Medicine has published research showing that down-regulation of NF-kB in the hypothalamus seems to slow our primary clock of aging. Work from the Ohio State University Wexner Medical Center implicates NF-kB over-activation as an important mechanism whereby cancers protect themselves from the immune system. Anecdotal evidence from anatabine citrate users supports that theory. If you haven’t watched this overview of the effects of anatabine citrate, you should. There has never been anything, drug or not, that produces this kind of benefits.
Anatabine citrate may be the best example of our system’s misplaced emphasis on diseases rather than aging. The company that owns the rights to the compound had to declare a disease target, but the FDA then used that fact to treat the natural substance as a drug. This, in turn, forced the company to withdraw it from the market. This is madness and people will suffer and die prematurely until we change the focus from diseases to the relatively easy and inexpensive ways of preventing them."
Article at:
http://www.mauldineconomics.com/tech/tech-digest/delayed-aging-is-the-ultimate-preventative-medicine
Longevity - Live to 140 Years of Age in Good Health ? at:
http://www.alkalizeforhealth.net/longevity.htm
Excerpt:
""The key to successful aging and longevity is to decrease chronic low-level inflammation without compromising an acute response when exposed to pathogens." - Dr. Claudio Franceshci
Why Isn't Google A Health Company? Look At Today's News in Forbes Pharma and Healthcare, 12/22/2014
Excerpts:
"Google is funding, within its walls, a biotech startup called Calico headed by Art Levinson, the legendary former Genentech CEO, to look for drugs to slow aging."
"The power to control drug prices in the U.S. now has shifted firmly to cost-cutting insurance carriers and pharmacy benefit managers. This means biotech companies, especially those facing competition, can’t guarantee the outsized profits investors have come to expect and crave."
Article at:
http://www.forbes.com/sites/matthewherper/2014/12/22/why-isnt-google-a-health-company-look-at-todays-news/
Ibuprofen use leads to extended lifespan in several species, study shows, Science Daily, December 18, 2014
Summary:
A common over-the-counter drug that tackles pain and fever may also hold keys to a longer, healthier life, according to a Texas A&M AgriLife Research scientist. Regular doses of ibuprofen extended the lifespan of multiple species.
Excerpt:
"Ibuprofen is a relatively safe drug that was created in the early 1960s in England. It was first made available by prescription and then, after widespread use, became available over-the-counter throughout the world in the 1980s. The World Health Organization includes ibuprofen on their "List of Essential Medications" needed in a basic health system. Ibuprofen is described as a"nonsteroidal anti-inflammatory drug used for relieving pain, helping with fever and reducing inflammation."
Polymenis said the three-year project showed that ibuprofen interferes with the ability of yeast cells to pick up tryptophan, an amino acid found in every cell of every organism. Tryptophan is essential for humans, who get it from protein sources in the diet.
"We are not sure why this works, but it's worth exploring further. This study was a proof of principle to show that common, relatively safe drugs in humans can extend the lifespan of very diverse organisms. Therefore, it should be possible to find others like ibuprofen with even better ability to extend lifespan, with the aim of adding healthy years of life in people.""
""Ibuprofen is something that people have been taking for years, and no one actually knew that it can have some benefits for longevity and health span."
HINT: Anatabine Citrate
Article at:
http://www.sciencedaily.com/releases/2014/12/141218141004.htm
Low glycemic diet does not improve risk factors for cardiovascular disease and diabetes in World Pharma News, 17 DECEMBER 2014
Excerpt:
""The study results were very surprising. We hypothesized that a low glycemic index would cause modest, though potentially important improvements in insulin sensitivity and CVD risk factors," explained Frank M. Sacks, MD, a physician and researcher in BWH's Channing Division of Network Medicine BWH and lead author of this study. "Our findings demonstrated that using glycemic index to select specific foods did not improve LDL cholesterol, HDL cholesterol, triglycerides, blood pressure or insulin resistance.""
Article at:
http://www.worldpharmanews.com/research/2970-low-glycemic-diet-does-not-improve-risk-factors-for-cardiovascular-disease-and-diabetes
"We may be able to reverse signs of early Alzheimer's disease"
By Stephanie Smith, CNN, December 8, 2014
Excerpts:
"Alzheimer's disease affects as many as 5 million Americans. It is the sixth leading cause of death in the United States, and there is no cure.
Yet a very small study out of UCLA is offering a glimmer of hope for those with what is often a hopeless diagnosis. Nine out of the 10 patients involved in the study, who were in various stages of dementia, say their symptoms were reversed after they participated in a rigorous program. The program included things like optimizing Vitamin D levels in the blood, using DHA supplements to bridge broken connections in the brain, optimizing gut health, and strategic fasting to normalize insulin levels.
A few months after starting the extreme program, patients in the study, aged 55 to 75, noticed their cognition had either improved or returned to normal. Only one patient, a 60 year-old female who was in the late-stages of dementia when she began the program, continued to decline.
The results, published this fall in the journal Aging, support the idea that addressing the many contributing factors of Alzheimer's disease as a group, rather than one at a time, could potentially reverse the disease's early progression, said study author Dr. Dale Bredesen, director of the Mary S. Easton Center for Alzheimer's Disease Research at UCLA.
Those factors include 36 potential deficiencies, imbalances and sources of inflammation.
"Each one of these things contributes a small piece of the puzzle," said Bredesen. "It's like a roof with 36 holes in it. Some people have a big hole in, say, exercise, and maybe a smaller hole in another area."
The 10 patients in the pilot study underwent a battery of tests, including having their blood drawn and brains scanned, and had neuropsychological evaluations. Bredesen said that most of the study participants had between 10 and 24 problems that needed correcting.
The effect of focusing on so many targets at once runs counter to what Bredesen said is a prevailing — and flawed — notion of identifying single targets to treat a disease caused by many factors.
"Drug companies tend to come up with a really good patch for one hole," said Bredesen, founder and CEO of the Buck Institute. "It's not a surprise they don't work."
Article at:
http://www.cnn.com/2014/12/08/health/alzheimers-reversal/index.html?hpt=he_t4
Roche fails AD trials follow-up: From Forbes: Beta-amyloid: "The emperor really does have no clothes"
Article at:
http://www.forbes.com/sites/davidgrainger/2014/12/20/beta-amyloid-the-emperor-really-does-have-no-clothes/
Bottom line: reducing beta-amaloid by itself does not improve cognition of AD patients.
"---Roche--- Alzheimer's studies fail" in Reuters, BY SILKE KOLTROWITZ AND BEN HIRSCHLER, ZURICH/LONDON Fri Dec 19, 2014
Excerpt:
"The Swiss drugmaker said it was ending a late-stage study of experimental Alzheimer's drug gantenerumab after it failed to prove effective, underlining the difficulty of treating the memory-robbing disease and removing "blue sky" upside for the shares."
Article at:
http://www.reuters.com/article/2014/12/19/us-roche-alzheimers-idUSKBN0JX0H620141219?feedType=RSS&feedName=healthNews
Is phase one completed and no one knows?
Excerpt from the Daily Reckoning article dated February 2013:
"Jonnie Williams, the CEO of a company dedicated to lessening the harm of tobacco, Star Scientific, discovered that extra ingredient. After spending years and millions of dollars to find a safe food form of the substance, he proved safety with two years of Harvard University toxicity studies. Then, he put smoking cessation mints containing his anatabine citrate on the market"
Article at:
http://dailyreckoning.com/a-natural-elixir-good-for-what-ails-ya/
Some history of Anatabloc re smoking cessation (sample searches):
"Star Scientific And Anatabloc: Does Anatabloc Really Work? Nuke John, Jun 10, 2013
Excerpt:
"Star has been selling an Anatabine based product called CIGRx for the past four years as a smoking cessation product, and it apparently has some ability to curb the urge to smoke brought on by nicotine addiction"
Article at:
http://seekingalpha.com/instablog/377272-nuke-john/1935502-star-scientific-and-anatabloc-does-anatabloc-really-work
Anatabine Significantly Decreases Nicotine Self- Administration
Nancy K. Mello, Peter A. Fivel, Stephen J. Kohut and S. Barak Caine
Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, Belmont, MA
Excerpt:
"Anatabine is one of the most abundant of the minor tobacco alkaloids but relatively little is known about its interactions with the abuse-related effects of nicotine. The acute effects of anatabine (0.18–3.2 mg/kg, IM) or saline on nicotine- and food-maintained responding were examined in four rhesus monkeys. Nicotine (0.01 mg/kg/inj, base) and banana-flavored food pellets (1g) were available under a second-order schedule (FR 2, VR 16:S). Anatabine or saline injections were administered 15 min before the food self-administration session began. Saline control treatment was in effect after administration of each anatabine dose until monkeys returned to baseline levels of responding. Anatabine dose-dependently reduced nicotine self-administration (P<0.05) with no significant effects on food-maintained responding. There was no evidence of sedation or other adverse side effects. These data suggest that anatabine could be an effective medication for treatment of nicotine addiction. Supported by DA026892 from the National Institute on Drug Abuse, NIH."
Article at:
http://www.fasebj.org/cgi/content/meeting_abstract/27/1_MeetingAbstracts/1098.8?sid=93577563-d249-4345-867e-b65c9bb52781
A Natural Elixir…Good for What Ails Ya! Patrick Cox, February 203
Excerpt:
"In fact, this alkaloid was discovered while searching for an effective smoking cessation aid. Researchers have long known that there’s more than nicotine in tobacco that leads smokers to smoke. This was obvious due to fact that smoking has powerful and pleasurable calming effects, via MAO inhibition, that nicotine does not provide. Moreover, despite the clear dangers of smoking, the tobacco plant has known medicinal values.
Jonnie Williams, the CEO of a company dedicated to lessening the harm of tobacco, Star Scientific, discovered that extra ingredient. After spending years and millions of dollars to find a safe food form of the substance, he proved safety with two years of Harvard University toxicity studies. Then, he put smoking cessation mints containing his anatabine citrate on the market."
Article at:
http://dailyreckoning.com/a-natural-elixir-good-for-what-ails-ya/
You can find more, just do a Google search: "stop smoking anatabine citrate"
Users Clinical Trial?
Post/email CIGX VIPGROUP from"
izof_texas@yahoo.com [CIGX_VIPGROUP] CIGX_VIPGROUP@yahoogroups.com
to CIGX_VIPGROUP
Sorry I'm late here, but overwhelmed. I did send my letter to the co. "proposing" what I hope they are already considering ... something that an attendee at the 2013 annual meet said Dr. Mullan had suggested possible when asked about "what if" they have to stop marketing the product.
I originally figured that the cost of such a move would be an insurmountable blockade, but research turned up the fact that there is no prohibition to charging for clinical trials. I acknowledged that there are many considerations, for example it would be a trial of hundreds, perhaps thousands, and there are things like liability. However in that vein I pointed out that these all would be people who are now dependent on anatabine for quality of life and, some, even life itself, and that that should be an extremely low risk cohort.
I proposed a very simple trial as a minimal "keep it going" measure: simply collecting ongoing reports of "yes" or "no" to the continuing question "Do you believe you have experienced any (undesirable) side-effects?" Even at that I allowed that I do not know, but perhaps each participant would have to be "seen" by someone at least once (but it would seem that for this perhaps not? Don't know.). Even at that, for those of us who receive great benefit from anatabine, a day's RT to Sarasota to have our temperature taken and blood pressure checked would be much less expensive than the alternative (for me about $9500 in assessment in 2009-10 and NONE since starting taking CigRx in fall 2010; for my "Crohn's patient", dangerous treatments ever escalating for age 14-18 to NONE since starting Anatabloc in October of 2011, and NORMAL colon function since, saving $10s of thousands a year). Perhaps an interview over the phone and vital signs taken at a local CVS, etc. would do.
It's probably a long shot still, but I just had to say something. A letter was sent to each of Dr. Chapman and Dr. Mullan. I'll include pertinent parts (most of it) below ...
##########
Dr. Michael Mullan, CEO
Rock Creek Pharmaceuticals, Inc.
2040 Whitfield Ave.
Suite 300
Sarasota, FL 34243
Dear Dr. Mullan:
....
Now to my specific purpose in this communication. There is a need, urgent to an extreme, for RCPI to make some accommodation for, and provision for, the probably several thousand persons who have come to depend on the anatabine citrate in Anatabloc to provide continuing and often complete relief from diseases of a very serious nature, ranging from Crohn's and ulcerative colitis to asthma to arthritis and so on.
I personally can attest to a case of Crohn's in a 17 year old girl (diagnosed at age 14, rapidly becoming severe and worsening) whose situation went from the likelihood of spending her senior year in high school having parts of her colon removed to a reality of virtual complete freedom from the disease, as attested to by her doctors, in the blink of an eye when she started a trial of just two Anatabloc a day (at my suggestion), with approval of her doctors (because she had nothing to lose). Her doctors in Dallas, TX had of course tried everything else available. (I presume, if need be, her doctors would attest to these facts with her permission, without reference to her specific case/personal information.)
This young woman is 21 years old now and is leading a normal life. Who among you at RCPI would be willing to explain to her that she is going to have to go back to living in Crohn's hell, and risk her life with likely repeated surgeries to remove parts of an organ that is functioning within the range of "normal" with the aid of anatabine citrate?
(Also) I ... [have someone near] who "is autistic". He swears by his perception of, and so do we observe, improvements in his ability to cope and function with use of anatabine citrate, though it is difficult to qualify/quantify precisely what the differences are, even as they are quite genuine and evident (from his relative ease, if nothing else). He is speaking of suicide if he has to continue on without it.
These are just two of dozens of examples I could cite. I know you have heard from dozens of others in similar situations, and indeed I too am yet one more of them. I hesitate to add to the clamor, and yet there is a truly dire necessity.
I must state, assert, and emphasize this point: there is nothing more urgent for RCPI to consider and to accomplish (simultaneously with the effort to develop the drug path) than to find a way to accommodate these people with a continuing supply of anatabine citrate until such time as it is available as a drug and can be prescribed for their purposes.That is an obligation that this company owes which is, if one counts the state of human suffering above other things, unparalleled by any other with the possible exception of the effort to assure company survival.
The company simply and absolutely must put forth every effort to find a way.
To that end I have explored this problem with what little time I've been able to make. I keep coming to the conclusion that there may be one way, and perhaps only one practical, totally above-board and legal way, to enable current users of Anatabloc to continue being supplied by the company. That would be by clinical trial. I am sure the company has also considered this [endnote 1]. I certainly hope that the company has such concerns.
With due respect acknowledged, in regard to the capabilities of our new and very knowledgeable management team, may I offer (to be taken or left) my thoughts on this matter just to ease my own concerns that something might somehow be missed in this consideration?
AN ONGOING CLINICAL TRIAL FOR ANATABINE USERS
In thinking along that line, my first concern was that this would necessarily be very costly for the company, but that appears to not necessarily be the case.
It appears that it is possible to conduct a clinical trial and have patients (and/or their insurance) pay for the medication, and even help to fund the study! There appears to be no exclusion of the situation in which the sponsor asks or requires the participants to pay for the medication under study, and/or pay for other costs also.
This came as a surprise to me, though I know that you and Dr. Chapman et. al. are likely aware. I found many references to this fact. I will assume that you are aware of such.
Thus it appears to be perhaps possible that the company could in fact conduct this trial in a low-loss or no-loss fashion, and perhaps could even make it profitable, although I would urge the company to do so minimally (say no more than 20%) if at all. If the latter (a profitable trial) were the case, there would certainly be no argument to arise regarding those of us who continue to support the company through investment in its stock and who also depend on anatabine citrate, and there appear to be dozens or hundreds of us.
If you think about it, were the company able to arrange a trial in which participants paid much or all of the costs, it would certainly be a high recommendation (to potential partners, for example) if the company could show that there are hundreds, perhaps thousands, of persons willing to pay, perhaps to the point of profitability, to participate in an ongoing clinical trial of its banner property.
Appearing to have found a path to possibly ease what I thought may be the biggest concern, that being cost, with the clinical trial approach, I spent some additional time thinking on this subject.
I propose that the company consider the design of a clinical trial for participants who can qualify by demonstrating (perhaps among other criteria) that they have taken the study substance (SS) anatabine citrate in one or the other of the company's supplements (perhaps requiring a show of order information, confirmation, receipts, the company's records, etc., if necessary). For the few that may not be able to produce such a record, perhaps an affidavit would suffice.
One option appears to be that the company could provide the SS to the participants at cost, but at true cost including G&A, manufacturing and study cost, etc. If it wouldn't ruffle feathers at FDA, perhaps a small profit could be allowed.
Legal Liability?
I am sure clinical trials carry some legal liability, but in this case the trial would be enabling continued help for people who are absolutely dependent on the SS for quality of life or life itself. I would think there could hardly be a lower risk cohort. Still this is a consideration, I know.
The Study/Trial
As to the nature of such as study, a very simple study, just seeking continuing input from participants as to side effects or lack thereof for example, or any other parameters that would pass muster with regard to the law and rules that govern such trials would do, if the only purpose of the trial were to allow those dependent on the SS to continue with an improved quality of life.
Of course there could be much more gained from more detailed input, but a minimal approach would distract the least from the company's main effort at present: drug development.
Not knowing the details governing such an effort, and without time to research at present, I do not know if such a trial absolutely requires that each participant actually be "seen" or examined in person at some point, though I suspect so, and I acknowledge that this could be quite a barrier to doing such a study, perhaps even if most of us were willing to travel to Sarasota at least once for such purpose (I can tell you that most of us would, indeed, be willing). Still, perhaps such cost (seeing participants once) could be covered by participants. It would be best of course if the remainder of the data could be collected over time by mail, say, with monthly or quarterly input (on provided forms) from participants (say a mere report of, or of no, side effects, on a continuing basis). Perhaps if not possible in that fashion, might telephone contact be sufficient?
I know that there are many aspects to such an effort, and that there may be barriers to such a one of which I am unaware. With little knowledge about the subject and no time to research further, I will (though I had written much more) abandon the discussion at this point for the sake of your time.
I hope that the company will investigate this possibility (ongoing clinical trial) to its completion immediately. If you can, it would certainly be welcome if you let the community of those who are dependent on anatabine citrate for quality of life know with all haste as to a decision on this matter (perhaps if possible via an SEC filing, if necessary so as to avoid having it be "publicity"), so that other possibilities (if there are any) may be explored if this one is barren.
Another possibility I considered is whether the company could simply, acting as a "chemical supplier" (for research purposes), supply the chemical, anatabine citrate, in a reasonably stable form (in tablets if possible, for stability's sake, but any stable form would do), with stated grade of purity (unstated: [at a grade] suitable for human consumption), perhaps in-state in Florida only if necessary (avoiding interstate commerce), and perhaps in "wholesale" amounts if necessary, at reasonable price. The company could disclaim that the compound thus supplied is not intended for human consumption. Please let me know immediately if this is possible, regardless of consideration of the previous possibility or any others.
There are indeed other chemical suppliers who offer other compounds of anatabine (tartrate for example), and one or more of them (online) even cite the research done by you (on the citrate compound), although they generally then state that the product, though "pure", is not for human consumption ... in a less than convincing fashion. One fear I have is that soon the public (previous takers in dire need) will be experimenting with these compounds, either spurring this as "another source" (albeit expensive at present) if experiences are good, or tarnishing the worth of our anatabine citrate if bad.
In any event, either the company alone, or working with those of us with greatest health concerns, must try to discover a way to accomplish this truly dire need, and soon. Time is of the essence.
Thank you most sincerely for your time, attention, and your presence as an officer of our company.
..........
1 In fact it was a quote from an attendee to the 2013 shareholders' meeting, who said that Dr. Mullan had suggested that possibility [of a clinical trial as a means] in answer to a question after the meeting concerning continuing supplying anatabine to those who needed it if the company were forced to stop marketing it as a supplement that gave me the idea.
Rock Creek Pharmaceuticals Announces Listing Extension on NASDAQ (company announcement)
Dec 11, 2014
Excerpt:
"SARASOTA, Fla., Dec. 11, 2014 /PRNewswire/ -- Rock Creek Pharmaceuticals, Inc., (NASDAQ: RCPI), a drug development company focused on chronic inflammatory disease and neurologic disorders, announced today that it received notification from the Nasdaq Stock Market, Inc. granting a six-month extension of its Nasdaq listing. The Company has until April 27, 2015 to maintain a closing bid price of at least $1.00 for a minimum of 10 consecutive days to maintain compliance with Nasdaq listing requirements. The extension is also subject to the condition that the Company
provide certain written updates to Nasdaq during the extension period and that Rock Creek file, on or before February 23, 2015, a preliminary proxy statement for a shareholder meeting for a reverse stock split proposal.
Rock Creek Pharmaceuticals
In addition, the Company has applied to transfer its listing from The Nasdaq Global Market to The Nasdaq Capital Market, which should go into effect on December 15, 2014. The Company believes that The Nasdaq Capital Market is better suited to smaller companies, such as Rock Creek Pharmaceuticals."
Announcement at:
http://investors.rockcreekpharmaceuticals.com/2014-12-11-Rock-Creek-Pharmaceuticals-Announces-Listing-Extension-on-NASDAQ
Sarasota scientists maybe find Alzheimer's breakthrough
Isabel Mascareñas, WTSP 8:25 p.m. EDT October 29, 2014
Excerpt:
"Roskamp scientists say until now, drugs have been able to target one of the three disease triggers at a time, either the beta amyloid buildup in the brain known as plaque, the inflammation or a protein called tau.
Crawford said, "Because it targets all three pathologies instead of a single pathology, we have increased enthusiasm it might show positive effect."
Click here to read the study published in The Journal of Biological Chemistry
Crawford says Roskamp's discovery gives researchers a new target to develop new drugs and the connection to the blood pressure medication makes sense.
"We know cholesterol, hypertension and other vascular factors do raise our risk for Alzheimer's disease," said Crawford.
Scientists began their study 10 years ago to see if Nilvadipine helped combat the plaque buildup in the brain. Scientists then realized the drug also suppressed another trigger -- the inflammation in the brain -- and that's when they tested the chemical on the third trigger, the tau protein. It worked, too.
Scientists started breaking down the molecule structure of the three triggers to see which components of the triggers reacted to the drug. They found one enzyme they call syk or spleen tyrosine kinase, crossed all three.
Clinical trials are underway involving 500 patients in nine European countries. If successful, scientists say there could be a drug within five years.
Susan says, "It might be ready! Oh my goodness it's so exciting, so exciting. You have to live for a little bit of hope."
Alzheimer's currently affects 5.2 million Americans, or 1 in 9 adults over the age of 65. The number of cases is expected to triple in the next 35 years, as Baby Boomers age.
The study by the Roskamp Institute will be published in the December issue of The Journal of Biological Chemistry"
Article at:
http://www.wtsp.com/story/news/local/2014/10/29/sarasota-scientists-maybe-find-alzheimers-breakthrough/18122749/
December 5th issue of 'The Journal of Biological Chemistry' article "The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-ß Production and Tau Hyperphosphorylation*
Daniel Paris1, Ghania Ait-Ghezala, Corbin Bachmeier, Gary Laco, David Beaulieu-Abdelahad, Yong Lin, Chao Jin, Fiona Crawford and Michael Mullan
Abstract:
"We have previously shown that the L-type calcium channel (LCC) antagonist nilvadipine reduces brain amyloid-ß (Aß) accumulation by affecting both Aß production and Aß clearance across the blood-brain barrier (BBB). Nilvadipine consists of a mixture of two enantiomers, (+)-nilvadipine and (-)-nilvadipine, in equal proportion. (+)-Nilvadipine is the active enantiomer responsible for the inhibition of LCC, whereas (-)-nilvadipine is considered inactive. Both nilvadipine enantiomers inhibit Aß production and improve the clearance of Aß across the BBB showing that these effects are not related to LCC inhibition. In addition, treatment of P301S mutant human Tau transgenic mice (transgenic Tau P301S) with (-)-nilvadipine reduces Tau hyperphosphorylation at several Alzheimer disease (AD) pertinent epitopes. A search for the mechanism of action of (-)-nilvadipine revealed that this compound inhibits the spleen tyrosine kinase (Syk). We further validated Syk as a target-regulating Aß by showing that pharmacological inhibition of Syk or down-regulation of Syk expression reduces Aß production and increases the clearance of Aß across the BBB mimicking (-)-nilvadipine effects. Moreover, treatment of transgenic mice overexpressing Aß and transgenic Tau P301S mice with a selective Syk inhibitor respectively decreased brain Aß accumulation and Tau hyperphosphorylation at multiple AD relevant epitopes. We show that Syk inhibition induces an increased phosphorylation of the inhibitory Ser-9 residue of glycogen synthase kinase-3ß, a primary Tau kinase involved in Tau phosphorylation, by activating protein kinase A, providing a mechanism explaining the reduction of Tau phosphorylation at GSK3ß-dependent epitopes following Syk inhibition. Altogether our data highlight Syk as a promising target for preventing both Aß accumulation and Tau hyperphosphorylation in AD."
Capsule
Background: Spleen tyrosine kinase (Syk) mediates microglial activation and neurotoxicity elicited by Alzheimer Aß peptides.
Results: Syk regulates Aß production via NF?B-dependent mechanisms and Tau phosphorylation by controlling the activation of glycogen synthase 3ß.
Conclusion: Inhibition of Syk can interrupt the neuroinflammation, pathological Aß accumulation, and Tau hyperphosphorylation in AD.
Significance: Syk represents a therapeutic target for the key pathological lesions that define AD.
Article at:
http://www.jbc.org/content/289/49/33927.abstract
Click on the name of the poster in question and you will get a page with the poster's IHub profile info. On the left side is a column with 'actions' you can take, including "Ignore This Member"
Maybe you haven't looked recently but I just looked and prices range from $100 to $185 per bottle and most are the 'mint' flavored tablets. You are correct that Anatabloc is available---for a price.
Got Arthritis? Out of Anatabloc? You might want to try this. Sent to me from a friend:
"Cure" For Knee Problem - "Osteoarthritis"
Some of you know that I have osteoarthritis stabilised by knee exercises and Glucosamine and Controntin
For the last 8 years while a few of my peers had knee replacement during this time. Last November I went to Hanoi Bay and did quite a bit of climbing that aggravated the pain in my right knee and started the pain in the left. Still I persisted with my medication and knee exercises. It gave relief up to 70%.
One of my favourite fruits is pineapple. I realize that for weeks since my trip to Hanoi I have not eaten any pineapple. I really missed that so went out to purchase one. Walloped one big piece heartily. Lo and behold, next morning when I started my exercises, the pain was nearly gone. There was around 95% relief. Thinking it was the benefit of the exercises I increased the momentum another 5 to 10 minutes.
Later in the day I began to think how could the pain decrease so much overnight.
Aha. only difference was the pineapple that I ate. Yes you guessed it, I went and walloped some more and obtained more relief. Back to before I went to Hanoi Bay. Happy but too shy to tell anyone until my sister rang up to inform of her back ache and unable to stand straight. Rebuked her for not doing anything like rubbing ointment or seeing a Dr. Jokingly informed her of my pineapple experience. Laughingly she said she was going to try that. A week or so later she came over and proudly showed me that she could walk straight without any pain. With thumb up she informed that the pineapple worked.
So friends if you or anyone you know have arthritis pain, pineapple is worth the try.
I dare to inform you after receiving this e-mail.
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The Effective Sweet Treat that Relieves Arthritis Pain
By Jim Healthy On October 19th, 2012
Did you know that there are certain kinds of foods that actually help reduce or even stop arthritis pain? These "superfoods" are usually easy to find and inexpensive.
Of all the foods that help fight against arthritis -- delicious, sweet pineapple comes up close to the top of the list.
THE SWEET PAIN RELIEVER
For generations, people around the world have used fresh pineapple to ease their arthritis inflammation.
Loaded with joint-protecting vitamin C, pineapple is undoubtedly a superior arthritis-healing food.
Its anti-inflammatory ingredient -- bromelain -- is so potent that many boxers drink the juice after fights to heal their bruises.
A 1960 study compared boxers who took bromelain with those receiving a placebo. In just four days, an amazing 78% of those taking bromelain were inflammation-free, while only 14% of the control group had recovered.
Other than bromelain, pineapple also contains manganese, which strengthens bones and protects joints.
Here are 5 reasons you should be indulging in this delicious fruit if you struggle with joint pain and arthritis:
Reason #1: Joint Protection
Higher intake levels of the antioxidant vitamin C is essential for people with arthritis... And just one cup of pineapple has a whopping 94% of the recommended daily allowance (RDA)!
Research published in the Annals of the Rheumatic Diseases showed that vitamin C-rich foods protect against inflammatory polyarthritis, a type of rheumatoid arthritis in which two or more joints are affected.
If you have osteoarthritis, you may be concerned by warnings that you should not increase your vitamin C intake. But know that those warnings are based on a 2004 study on guinea pigs!
Studies on humans show vitamin C actually reduces pain, cartilage loss and disease progression.
Reason #2: Healthier Joint Tissue
Pineapple is a great source of the trace mineral manganese.
Manganese is absolutely essential for building healthy joint tissue and dense bones. One cup of pineapple provides 128% of the RDA for manganese.
Research shows that manganese tackles free radicals that can damage joint cartilage.
Tip: It's best to eat your pineapple raw. Fruit skewers alternating fresh pineapple chunks with strawberries is a great way to do that. Grilled and cooked pineapple is extraordinarily tasty too.
Reason #3: Smoother Joint Movement
Pineapple's enzymes literally clean up "rusty" joints. When you eat pineapple on an empty stomach, the enzymes go right to work on your joints.
Tip: If you eat pineapple with other foods, the enzymes divert their activity to digesting the rest of your meal instead of the gunk in your joints.
So keep pineapple around for between-meal snacks. Juice the hard inner core as well to take advantage of the concentrated bromelain located there.
#4: Pain Relief
For optimal arthritis pain-relief, eat fresh pineapple. The bromelain in pineapple is destroyed by heat, so fresh pineapple will give you the most benefit.
Frozen pineapple retains active enzymes but canned fruit and commercially processed juice don't provide the anti-inflammatory benefit of fresh fruit.
It's important to note bromelain causes anti-clotting activity...
So you should consult with your physician before combining pineapple with blood-thinning medications such as warfarin (Coumadin), heparin or aspirin.
Tip: If the fruit needs to ripen, keep it on your kitchen counter for a couple days. You'll know it's sweet and ready to eat when the bottom softens a bit.
Reason #5: Protection from Inflammation
Pineapple's bromelain halts inflammation. The sulfur-based enzyme bromelain in fresh pineapple is one of the best-researched natural anti-inflammatory agents around.
Bromelain clobbers inflammatory agents that trigger joint pain and cartilage degeneration.
A 2006 study cited in Clinical and Experimental Rheumatology found that supplemental bromelain is effective in easing discomfort from hip arthritis.
The Arthritis Foundation stated that pineapple's bromelain produces effects comparable to NSAIDs for relieving pain and inflammation.
UK researchers reviewed ten studies on osteoarthritis and bromelain. They found that every single one confirmed bromelain's benefits.
Tip: Most of the bromelain in pineapples is found in the core and the stem. So don't throw away that tough, fibrous core!
Just chop it up, throw it in a blender with some water and pulse to convert it to juice."
Haysaw, great info, I printed me a copy for reference
My brother the pharmacologist said: "They would not be required to meet purity and composition requirements for human consumption"---so be aware
Reference page for 'drugs' and 'supplements'.
Excellent compilation of both subjects at Medline Plus which is a service of the U.S. National Library of Medicine
From the National Institutes of HealthNational Institutes of Health
My comments: interesting that several supplements have the same MO as Anatabloc but Anatabloc gets singled out as a 'drug'. Only the infinite wisdom of the FDA can make that distinction.
http://www.nlm.nih.gov/medlineplus/druginformation.html
FDA definition of a drug:
"Drug
A drug is defined as:
A substance recognized by an official pharmacopoeia or formulary.
A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.
A substance (other than food) intended to affect the structure or any function of the body.
A substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device.
Biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process versus biological process.)
Drug Product
The finished dosage form that contains a drug substance, generally, but not necessarily in association with other active or inactive ingredients.
Drug Product
The finished dosage form that contains a drug substance, generally, but not necessarily in association with other active or inactive ingredients."
So, by the FDA definition, Anatabloc is a drug. Anatabine Citrate is a chemical compound and molecule. Anatabloc active ingredients are:
Anatabine Citrate, Vitamin A, and Vitamin D3
If you want to find out more about FDA definition of drugs, go to:
http://www.fda.gov/Drugs/InformationOnDrugs/ucm079436.htm
I suggest you use Google search more and you will find your answers to many of your questions that you post. You might also find useful information passed on by other contributors that have previously posted.
I can't answer your question but on the page that lists Anatabine, there is a warning:
"Warning This product is not for human or veterinary use."
The 'Product Information' page describes it as for use in laboratory research, it comes dissolved in ethanol. I guess if you tried this stuff, you could get drunk too and kill two birds with one stone.
I will ask my brother who has a PhD in Pharmacology about it and post any feedback he has to enlighten us with.
Product Info Page"
https://www.caymanchem.com/pdfs/11001.pdf
This post was in response to the question:
"Has Rock Creek applied for anatabine use patent for Alzheimer's?"
posted by idcc2006
I excerpted the part of the patent that showed RCPI had included Alzheimers in their 'use and synthesizing (manufacture)' patent.
You should read the link posted to understand the extensive coverage of the patent.
Patent description at:
http://patentscope.wipo.int/search/en/detail.jsf?docId=WO2011119722&recNum=2&maxRec=21&office=&prevFilter=&sortOption=Pub+Date+Desc&queryString=FP%3A%28rock+creek+pharmaceuticals%29&tab=PCTDescription#