Most Sirtuin Investor Readers Using Resveratrol

The SI Blog Resvertrol Usage Poll is has closed. Not suprisingly 80% of those polled are taking resveratrol. Almost 1/2 of those polled are taking in excess of 200mg per day. Here are the final results:

I don't take any --- 19%
Up to 100 mg ----- 11%
Up to 200 mg ---- 20%
Up to 1,000 mg -- 26%
Over 1,000 mg --- 22%

Given that Sirtris dosed at 5,000 mg and 2,500 mg in its recent Type 2 Diabetes clinical trial without any significant adverse effects it does not seem surprising that those somewhat knowledgable about sirtuins are taking rather high doses.

Cancer and Sirtuins: Activate or Supress??

There seems to be some conflicting ideas with regard to targeting sirtuins to fight cancer. Sirtris is researching how activation of sirtuins can stop cancer growth while others are looking to de-activate sirtuins to achieve the same result:

From Sirtris 2/20/08:

CAMBRIDGE, Mass., Feb 20, 2008 (BUSINESS WIRE) -- Sirtris Pharmaceuticals, Inc.
(NASDAQ: SIRT), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced that Sirtris co-founder David Sinclair, PhD, Harvard Medical School Associate Professor of Pathology, will present data showing that SIRT1 activation can suppress tumor formation and growth in the intestine and colon in a preclinical model of colon cancer. These are the first in-vivo data showing that SIRT1 overexpression can suppress tumor formation and growth. These data are the work of Sirtris Scientific Advisory board co-chairs Sinclair and Leonard Guarente, PhD, the Novartis Professor of Biology at the Massachusetts Institute of Technology

From Sirtris 2/21/08:

The National Cancer Institute will test the compounds in well-established cancer cell lines which were previously used in the development of novel and existing chemo-therapeutics. The cell lines to be tested include some of the most common cancer types. The program will also test Sirtris' compounds using in-vivo mouse tumor models to determine if the compounds reduce or limit the growth of the tumor cells. Previous studies have shown that calorie restriction--a method which has been shown to increase SIRT1 activation--can exert strong tumor suppressor effects in mammals and increase lifespan in organisms. Through direct activation of the SIRT1 enzyme with Sirtris' compounds, researchers in this study will be able explore the enzyme's role in tumor suppression along multiple pathways.

Exerpt from From University of Bath press announcement (undated, but recent):

"...Studies have shown that increased levels of these enzymes, known as sirtuins,
are found in tumours from a range of different cancer types.

This suggests that, by finding a way of preventing these enzymes from working, it may be possible to halt the progression of cancer by stopping tumour cells from
dividing and growing. "

Sirtuins In Men's Skin Beauty Product??

Sirtuin activation has now found its way into men's high end skin care products as a company called Alford & Hoff has jumped on to the band wagon. As sirtuin research expands exponentially and continues to show expanding potential health benefits, the roster of companies looking to capitalize also continues to expand. Are we in the early stages of a mania? Time will tell. An interesting aspect of this sirtuin based product expansion is whether any of these companies are researching patent infringement issues before coming to the market. The other angle is whether these products really do anything!

Chris Westphal Comments on Stock Price

At the BIO CEO & Investor conference today, Chris Westphal commented on the stock price action of SIRT since the IPO. He mentioned how the stock rallied strongly after the IPO and corrected down significantly after the 6 month lock-up expired and venture capitalists sold off 20% of the market capitalization over the last six weeks. Of most interest to the Sirtuin Investor was his comment regarding SIRT's stock price... "...has corrected down significantly. We view this as a buying opportunity for the company."

I'm glad to hear Dr. Westphal say this and I expect that he and other top SIRT employees will refrain from any further insider sells, 105b-1 plan or not, for the forseeable future as discussed in previous blog entry dated January 31st.

SRT501 Not Likely a Stand Alone Type 2 Diabetes Drug

In the Q&A at the BIO CEO & Investor Conference, Christoph Westphal mentioned that SRT501's future as a drugable treatment of Type 2 Diabetes may lie in the pairing of it with other drugs such as metamorfin. The NCE, which is 1,000 times more potent than SRT501, is viewed within the company as the better candidate for stand alone type 2 diabetes treatment. Data in the next few months should provide the information necessary to make this determination on SRT501.

Do your own DD.

SRT501 To test Against Cancer in 2008

At the BIO Investor & CEO Conference today, Dr. Chris Westphal disclosed that Sirtris Pharmacueticals would commence SRT501 clinical trials in humans for the treatment of cancer. He mentioned that many resveratrol studies have shown effects on cancer.

From Wikipedia:

Cancer Prevention
In some lineages of cancer cell culture, resveratrol has been shown to induce apoptosis, which means it kills cells and may kill cancer cells.[35][36][37][38][39][40] Resveratrol has been shown to induce Fas/Fas ligand mediated apoptosis, p53 and cyclins A, B1 and cyclin-dependent kinases cdk 1 and 2. Resveratrol also possesses antioxidant and anti-angiogenic properties.[41][42]

Resveratrol is under extensive investigation as a cancer chemopreventive agent.[43][44] Indeed, there are studies showing that small doses of dietary resveratrol can reduce colon carcinogenesis in rats and mice.[45] One German study has already been shown to that under special conditions, resveratrol induces apoptosis in human fat cells. In addition, it inhibits production of cytokines which are involved in the development of obesity-related disorders.[46]

Do your own DD.

Hopping onto the Sirtuin Bandwagon

We are now seeing other groups hopping onto the sirtuin bandwagon. Here are a couple of non profit research centers, one in India and one in PA that are combining forces in the area of sirtuins.

Press Release
Wistar on Sirtuins

SI projects that before this year is done we will begin to see one or more OTC Bulletin Board stocks pop up (probably through reverse mergers) with no real hope of commercial success but with fantastic claims of grandeur. Their press releases will focus on the huge size of the market of drugs related to diseases of the aging. It happens all the time once a great idea catches fire.

Basic Foundation of Type 2 Diabetes Treatment Crumbles

In a startling development in Type 2 diabetes treatment, a wide held pillar of belief that aggressively keeping one measure of blood sugar (called HbA1c) below 6 instead of the standard 7.5 would reduce heart attacks and other cardiovascular events has crumbled. Businessweek has a very thorough article on this startling development.

How this will effect Sirtris Pharmaceutical’s SRT501 and NCE diabetes drug candidates cannot be known at this time. However, I find this excerpt from the Businessweek article particularly interesting:

"However, the evidence that aggressive blood sugar control using drugs brings benefits has always been weak. Proponents of more intensive drug treatment cite a landmark study started back in the 1970s called the U.K. Prospective Diabetes Study (UKPDS). In that trial, researchers followed thousands of patients with type 2 diabetes for more than a decade, comparing those who merely got advice on diet and lifestyle to those who took drugs to lower their blood sugar and keep it under tighter control. The researchers claimed the more aggressive treatment worked to reduce the complications of diabetes, which include kidney failure, blindness, amputation of infected limbs, and cardiovascular disease.

But in fact, the benefits seen in the trial were tiny or nonexistent. The study's authors had to torture the data to reach their conclusions, charges Dr. Robert Ewart, associate professor of family and community medicine at Southern Illinois University School of Medicine. "The UKPDS was a particularly egregious example of data manipulation," he says. "There just isn't any evidence that tight control of type 2 diabetes improves outcomes."

Ewart has plenty of company in doubting the trial. No oral diabetes drug "has ever been shown to do anything really good for any patient," adds Dr. Nortin Hadler, professor of medicine at the University of North Carolina at Chapel Hill. "No leg, eye, kidney, heart, or brain have ever been spared." And in a recent New England Journal of Medicine commentary, Dr. Clifford Rosen, chair of the Food & Drug Administration advisory committee that evaluated one such drug (GlaxoSmithKline's (GSK) Avandia), wrote that "the two largest randomized, placebo-controlled trials in patients with type 2 diabetes, the United Kingdom Prospective Diabetes Study and the University Group Diabetes Program, failed to find a significant reduction on cardiovascular events even with excellent glucose control.""

It is nearly impossible to come to any firm conclusions, with any level of certainty, that can interpret this new data. However, no one can argue that the best treatment for type 2 diabetes is what most humans seemingly don't want to hear: EAT LESS AND EXCERCISE MORE! In other words, live a healthy lifestyle. That is where it seems that targeting sirtuins may have advantages over other drug treatments. The basic premise behind sirtuin research is that the activation of certain sirtuins can mimic a calorie restriction diet (CRD). Long time readers on this blog understand that there are many studies that indicate that a CRD has been proven to increase longevity and fight off disease in many mammals (new readers should review early entries on the SI blog to learn about CRD). Could it be that mimicking a healthy diet may be the best way to treat Type 2 Diabetes for those who cannot live a healthy lifestyle on their own? Only time will tell. Interesting stuff.

Sirtris Signs Leonard P. Guarente to Exclusive

Sirtris Pharamcueticals today announced today Leonard P. Guarente, PhD, Novartis Professor of Biology at the Massachusetts Institute of Technology, has signed a new, exclusive consulting agreement with Sirtris Pharmaceuticals. Dr. Guarente first joined Sirtris’ Scientific Advisory Board as Co-Chair in November 2007. Prior to joining Sirtris, Dr. Guarente was formerly a co-founder of Cambridge, Mass. based Elixir Pharmacueticals, another sirtuin focused startup. Elixir recently postponed its planned IPO. Sirtris has establish a leading edge roster of sirtuin research expertise and this new agreement further solidifies its position.