Star Scientific (STSI):
The tortuous history of drug discovery and development is filled with examples of long, quirky, unpredictable and often serendipitous discoveries and then, much as the substance in a mosaic reveals itself, its relevance and significance becomes vibrantly clear. To view a celebrated tesserae link here.
Major medical breakthroughs never happen overnight. Science marches to the beat of its own drum, and discoveries typically emerge over the course of years, decades, or even centuries, before culminating in disruptive technologies and important medical advances.
A striking example of a major medical advance occurring over a long timeline is the discovery and development of statins, the class of medicines that are now the first-line treatment for lowering cholesterol levels. In the late 1800s, German scientist Rudolf Virchow discovered that large amounts of cholesterol were deposited on the artery wall of patients who died from cardiovascular disease. Fast forward 50-years to the celebrated Framingham heart study, which demonstrated a correlation between blood cholesterol levels and coronary heart disease. Yet it took another 20 years until Japanese researchers discovered the first compounds that inhibited the biosynthesis of cholesterol in the 1970s, and still another 20 years until the development of Lipitor, the biggest selling medicine off all time. Lipitor sales exceeded $12.8 billion in 2006 alone, and have been worth over $100 billion to Pfizer (PFE) since receiving FDA approval in 1996. Aside from the astonishing sales figures, the statins have saved countless lives by preventing hyperlipidemia and associated cardiovascular diseases.
The story of anatabine, the active component of Star Scientific's Anatabloc, is no different. The science has been evolving for over 25 years, and Anatabloc has been unequivocally demonstrated to effect many important pathways of inflammatory, neurological, and autoimmune diseases such as rheumatoid arthritis, Alzheimer's disease, and Parkinson's disease. Let's take a retrospective examination of the science, the timeline, and at what we now know, and then look toward to what the future holds.
1988 - Researchers at the University of Colorado Health Sciences Center in Denver found that smoking slowed disease progression in ulcerative colitis patients, with lower rates of flares-ups and hospitalization. They published their findings in The Scandinavian Journal of Endocrinology. Link here.
1998 - The Mayo Clinic publishes positive results of a clinical trial using nicotine as a treatment for ulcerative colitis. "Ulcerative colitis is predominantly a disease of nonsmokers. Transdermal nicotine may help control clinical manifestations of this condition." Link here.
1999 - A publication in the British Journal of Clinical Pharmacology describes the positive effects of tobacco use in patients with inflammatory bowel disease. "…there is overwhelming epidemiological evidence that smoking protects against ulcerative colitis, the risk of developing the disease being significantly lower in smokers than in non-smokers or former smokers." Link here
2003 - Dr. Paul Ladenson, directory of the division of Endocrinology at Johns Hopkins, discloses the results of a large epidemiological study on over 16,000 people demonstrating that tobacco use has a beneficial effect on autoimmune thyroid conditions such as Hashimoto's disease. Link here
2004 - Dr. Paul Ladenson and his team at Johns Hopkins publish the results of a study conducted among a group of flight attendants with chronic exposure to cigarette smoke. This pivotal study found a reduction of autoimmune thyroiditis (Hashimoto's disease) related to inhalation of second hand cigarette smoke. The link to the Johns Hopkins / Ladensen study of 18,148 persons who underwent thyroid testing here.
2007 - A Harvard School of Public Health study showed that smokers were 73% less likely to suffer from Parkinson's than people who didn't smoke. According to Dr. Honglei Chen, the study's lead researcher "the information could guide the development of studies on various tobacco components ... to help understand the relationship between smoking and Parkinson's disease … further research could determine which chemicals are responsible for bolstering the brain against the illness." Link here.
2009 - 2010 - Researchers at Star Scientific discover that anatabine, one of the 4,000 chemicals found in tobacco, has the capacity to reduce the urge to smoke. Scientists at Star have subsequently determined that anatabine, the active ingredient in Anatabloc, has numerous additional benefits and is likely the key active component of tobacco responsible for its positive effects on autoimmune and inflammatory diseases.
2010 - Harvard University's McLean Hospital completes a comprehensive two year preclinical research program demonstrating the safety and tolerability of anatabine, as well as complete lack of addictive potential. Link here.
October 2010 - The Roskamp Institute begins clinical trials of RCP-006 (anatabine) for the treatment of Alzheimer's disease. In addition, Roskamp scientists begin a collaboration with Johns Hopkins to investigate additional therapeutic applications of RCP-006. Links here and here.
March 2011 - Star Scientific files an international patent application (WO 2011/119722 A2) describing the use of anatabine to lower key inflammatory biomarkers. From the summary: "A pharmaceutical composition comprising a therapeutically effective dose of an isolated form of anatabine or a pharmaceutically acceptable salt thereof can be administered to an individual to reduce a symptom of a disorder comprising an NF-kB mediated inflammatory component or to reduce the risk of developing such a disorder."
March 2011 - The Roskamp Institute demonstrated the striking anti-inflammatory effects of anatabine, as evidenced by the reduction of key pro-inflammatory cytokine IL-1beta. Anatabine was shown to over three times more effective than Lipitor at lowering this marker of inflammation. Link here.
July 2011 - Researchers at The Roskamp Institute disclose the results of a study demonstrating that anatabine (RCP-006) is over four times more effective than both Celebrex and Voltarol in reducing levels of damaging pro-inflammatory cytokines. Link here.
August 2011 - Star Scientific begins marketing of Anatabloc via a dedicated product website.
September 2011 - The Roskamp Institute demonstrates anatabine's ability to decrease LPS-induced NF-kB activity. More importantly, anatabine was shown to be effective at dose equivalent levels where Celebrex and aspirin demonstrate severe toxicity. Link here.
November 2011 - Researchers at The Roskamp Institue publish a peer-reviewed manuscript in the European Journal of Pharmacology entitled "Anatabine lowers Alzheimer's Aβ production in vitro and in vivo." For a brief abstract link here.
January 2012 - Star reports first completion of clinical trial showing anatabine lowers chronic inflammation measured by C-reactive protein [CRP] blood levels in humans. Up to this point in the timeline there had been no clinical evidence that anatabine worked as well in human studies as it did in cell and animal studies. Link here.
May 2012 - Researchers at the Roskamp Institute completed a successful animal study of nutritional supplementation anatabine in an animal model of multiple sclerosis (MS). Preliminary data all suggest the company's specially formulated anatabine supplement has a highly beneficial effect in this model of MS. Link here.
July 2012 - A team led by Dr. Paul Ladenson publish a peer-reviewed manuscript in the Endocrinology journal entitled "Anatabine Ameliorates Experimental Autoimmune Thyroiditis." The team found that anatabine was able to completely prevent the (thyroid) disease in many mice and significantly reduce the severity of disease in the entire population that received the treatment. In addition, the team found that the treatment with anatabine significantly reduced the presence of numerous proinflammatory agents such as interluken-1 receptors, interluken-18, COX2, and others. Link here.
September 2012 - Star Scientific launches Anatabloc face cream "that's been demonstrated to considerably improve the appearance of the skin in a broad variety of volunteers in a case series conducted by leading dermatologist Dr. Susan H. Weinkle of Bradenton, Florida, past President of the American Society for Dermatologic Surgery." Link here.
October 2012 - Researchers at the Roskamp Institute reported that in the "Flint" CRP study that "11 of 18 (61%) diabetic subjects on metformin (the first-line drug of choice for the treatment of type 2 diabetes) had a CRP reduction, as did 31 of 81 (38%) subjects in the general trial population not taking metformin. Overall, 42 of 99 (42%) subjects had a decrease in CRP after only one month with anatabine supplementation." The committee reviewing the data found that "the administered doses of anatabine were safe, well-tolerated, and showed clear evidence of a biological effect on CRP and the immune system, as manifested by CRP and an inflammatory marker called Tumor Necrosis Factor Alpha (TNF-alpha)." Link here and here.
January 2013 - Researchers at the Roskamp Institute publish a peer-reviewed manuscript in the European Journal of Pharmacology (EJP) entitled "Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation." The study demonstrated the effect of anatabine on the JAK-STAT pathway by suppressing STAT3 phosphorylation, inhibiting TNF-alpha and NF-kB levels in-vitro. Link the EJP abstract here. See an informative video re JAK-STAT link here.
January 7, 2013 - Star Scientific / Rock Creek Pharmaceuticals publish positive preliminary results of their research entitled "Anatabloc Supplementation Autoimmune Prevention." Results from the trial disclose that the anatabine science has demonstrated proof of concept and efficacy in all human study subjects in trials supervised by the distinguished physician / scientist Dr. Ladenson, as senior endocrinological consultant for the study. Link here.
January 30, 2013 - Researchers at the Roskamp Institute publish a peer-reviewed manuscript in PLOS ONE entitled "Amelioration of Experimental Autoimmune Encephalomyelitis (EAE) by Anatabine." The abstract revealed that; Orally administered anatabine markedly suppressed neurological deficits associated with EAE while significantly reducing Th1 and Th17 cytokines known to contribute to the development of EAE. Anatabine appears to significantly suppress STAT3 and p65 NFκB phosphorylation in the spleen and the brain of EAE mice and found that anatabine alleviated the infiltration of macrophages/microglia and astrogliosis and significantly prevented demyelination in the spinal cord of EAE mice. To view the 26 page PLOS ONE peer-review, link here.
The science of anatabine / Anatabloc has now progressed from lab bench through animal models and recently into the clinic with humans demonstrating success at every stage signifying clear signals of efficacy in major disease areas, and no - absolutely no adverse events related to toxicity. All the scientific and clinical data indicates that the compound is safe, effective and well tolerated. As interest compounds exponentially in the scientific and medical community, with clinical and anecdotal evidence piling up, anatabine / Anatabloc is taking its rightful place front and center in the fight against "inflammaging" driven by immunological and inflammatory diseases. One can only imagine what the future holds.
Because of the length of this report "What We Know / and Beyond" will be addressed in a following report.