Re: [GRG] Dasatinib + Quercetin gerotrial?…

Edward,

Before any human studies in gerontology are done, I’d suggest very careful evaluation of the risk and etiology of the primary pulmonary hypertension (PPH) seen in a significant number of patients receiving 140 mg QD dose for cancer. I want more time and all the help I can get running that one to the ground. PPH is a uniformly fatal and very unpleasant way to die that is curable only by lung transplant, should you be lucky enough to get one and to live through the surgery and anti-rejection regimen. The myelodepressive and pleural effusion effects of dasatinib appear dose and time course related, and while of concern, are of less concern at such a low dose and (presumably) short duration of Tx. 

However, PPH is strange animal – a very strange animal. It is associated with a number of medications, as well as the chronic intermittent hypoxia of sleep apnea. Most cases are idiopathic, meaning the etiology is not known. The concern here is that it may result from alterations in receptor morphology, biochemistry, or from changes to the biochemistry of the pulmonary vascular endothelium, or even to central regulatory mechanisms that control lung capillary tone. As such, in cases of drug induced PPH, this adverse effect can sometimes occur over a wide range of doses. Thus, the incidence of PPH may not be a function of dose above a relatively small amount, and the same may be true of duration of Tx. I also suspect this only happens in humans.

What we really need is the Phase 1 and Phase 2 clinical trials data wherein they were doing dosage escalation studies. These trials are all about safety (especially Phase 1), rather than efficacy. Thus, I suspect the doses used in these initial studies were likely to have been in the range of 50 to 75 mg QD. The incidence of myleotoxicity and of PPH, if any, would thus be very indicative.

If you, or anyone else knows how to get this data, well then you should get it, LOL, and post it here or send to me, or both.

Mike Darwin

PS, if there is going to be a trial involving 20-30 people, it would be worthwhile to try and get the drug purchased in India and shipped to the U.S. via courier, such as Blue Dot. The current price in India is approximately $55 per 50 mg tablet and $104 per 100 mg tablet, or about $1.00 milligram. This is the OTC pharmacy price where you walk in the door and Kay your money on the counter: no RX is required in India. With those savings, you could afford to fly someone to Mumbai, just to make the purchase! I’ll check with my friends in India and see if any would be willing to make the purchase and do the shipping, presumably for a small “hassle fee”, though this unlikely. The biggest risk is theft en route, which the Indian pharmacies that supply the U.S. get round by paying generous bribes. 

PPS, the intrinsic cost of producing this molecule is almost nil. Cipla offered to produce dasatinib for $4.00 per adult dose, however U.S. pressure on the Indian government was successful in preventing this. 

MD

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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