SIRT Sierra Natl BK Tehachapi Calif (MM)

Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced that a research team led by the company�s two Scientific Advisory Board co-chairs has demonstrated that overexpression of the SIRT1 enzyme can suppress tumor formation and growth in a preclinical mouse model of colon cancer, providing the first in-vivo data that SIRT1 can suppress tumor cell development. The paper, titled SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth, appears in today�s issue of the scientific journal PLoS One. �Research data suggest that calorie restriction (CR), which is known to cause SIRT1 expression, has a tumor suppressive effect in mammals,� says paper co-author David Sinclair, PhD, Sirtris Scientific Advisory Board Co-Chair and Associate Professor of Pathology at Harvard Medical School. �In this study, we proposed that the SIRT1 enzyme is responsible for many of the effects of CR, including tumor suppression.�This study clearly shows that SIRT1 can suppress tumor development and may mediate the effect of CR. Sirtris plans to initiate a cancer trial in humans in the second-half of this year.� �Additional studies are underway to determine other cancer models where SIRT1 overexpression may suppress tumor development,� says paper co-author Leonard P. Guarente, PhD, Sirtris Scientific Advisory Board Co-Chair and the Novartis Professor of Biology at the Massachusetts Institute of Technology. The research team tested a strain of mice that physiologically mimics the early events of human colon cancer. A mutation in the strain allows the protein B-catenin to localize in the nucleus of cells and initiate a pathway that drives unchecked cell proliferation. Activation of the B-catenin pathway has been found in 90 percent of colorectal cancers, and is also activated in other cancers, including prostate, breast, ovarian and melanoma. The team chose this particular strain of mice because previous research showed that calorie restriction in this strain could slow tumor development. They bred the B-catenin colon cancer mice with mice that overexpress the SIRT1 enzyme in the gut. At four months of age, the SIRT1 overexpressing mice had a three- to four-fold reduction in the number and size of adenomas. Adenomas are benign growths, but over time may progress to become malignant. The research team also found that the adenomas found in SIRT1 overexpressing mice had a significant reduction in Ki-67, a protein expressed in proliferating cells, used as a marker for tumor growth. At 16 weeks of age, the study�s control mice�those that did not overexpress SIRT1�began to show signs of weight loss, fatigue, loss of appetite, weakness and anemia, which occurs when the level of healthy red blood cells in the body becomes too low. The SIRT1 overexpressing mice did not display such overt signs of sickness. The research team then demonstrated that the reduction in tumor development was caused by the ability of SIRT1 overexpressing mice to suppress B-catenin. Using human colon cancer cell lines whose growth is driven by active B-catenin, the team was able to greatly reduce cancer cell proliferation with increased SIRT1 expression. In another cell line, the researchers were able to show that SIRT1 promoted the deacetylation and inactivation of B-catenin. B-catenin, when found in large amounts in the nucleus of tumor cells, is associated clinically with poor patient prognosis. The team examined 81 human colon cancer tissue samples to determine the relationship between SIRT1 and B-catenin expression. There was a significant inverse relationship between the level of SIRT1 expression and the levels of B-catenin in the nucleus of these cancer cells. �This research suggests that SIRT1 activation is a potential therapeutic avenue for certain cancers,� says Sirtris Pharmaceuticals Chief Executive Officer and Vice Chair, Christoph Westphal, MD, PhD. �Our recently announced research effort with the National Cancer Institute to test our SIRT1 activators in multiple cancer models, as well as ongoing work by these investigators, will help guide our programs.� About Sirtris Pharmaceuticals Sirtris Pharmaceuticals is a biopharmaceutical company focused on discovering and developing proprietary, orally available, small molecule drugs with the potential to treat diseases associated with aging, including metabolic diseases such as Type 2 Diabetes. Our drug candidates are designed to mimic certain beneficial health effects of calorie restriction, without requiring a change in eating habits, by activation of sirtuins, a recently discovered class of enzymes that the Company believes control the aging process. Sirtris Pharmaceuticals is engaged in human clinical trials for Type 2 Diabetes, and is planning similar trials in cancer, another age-related disease. Sirtris is also engaged in a human clinical trial for MELAS syndrome, a mitochondrial disorder. The company's headquarters are in Cambridge, Massachusetts. This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, the potential therapeutic effects of SIRT1 expression and activation for diseases of aging, such as Type 2 Diabetes and Cancer; the progress, timing and results of preclinical and clinical studies of SIRT1 activators; the success of new therapies for Type 2 Diabetes and Cancer; and the potential of sirtuin modulators to receive regulatory approval. These forward-looking statements about future expectations, plans and prospects of Sirtris Pharmaceuticals involve significant risks, uncertainties and assumptions, including risks related to the lack of results that would provide a basis for predicting whether any of the Company's product candidates will be safe or effective, or receive regulatory approval, the possibility that results of preclinical studies are not necessarily predictive of clinical trial results, the Company's potential inability to initiate and complete preclinical studies and clinical trials for its product candidates, the fact that none of the Company's product candidates has received regulatory approvals, the potential inability of the Company to gain market acceptance of the Company's product candidates, and those other risks factors that can be found in the Company's filings with the Securities and Exchange Commission. Actual results may differ materially from those Sirtris Pharmaceuticals contemplated by these forward-looking statements. Sirtris Pharmaceuticals does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release.