Sierra Natl BK Tehachapi Calif (MM) (NASDAQ:SIRT)
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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.