Sirtris Pharmaceuticals, Inc (SIRT), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced that the United States Food and Drug Administration has granted the company orphan-drug designation for resveratrol in the treatment of MELAS syndrome (Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). Orphan-drug designation for resveratrol in MELAS syndrome provides Sirtris with seven years of marketing exclusivity upon receipt of FDA approval.

"MELAS can have a devastating effect on the quality of life of patients and their families," says Professor Patrick Chinnery of Newcastle University, who is leading a MELAS phase 1b clinical trial in the United Kingdom with SRT501, Sirtris' proprietary formulation of resveratrol. "Finding treatments for MELAS and the many other mitochondrial-related illnesses is essential," says Chinnery, whose focus is the treatment and research of mitochondrial disorders.

"Many diseases of aging, such as type 2 Diabetes, exhibit impaired mitochondrial function," says Peter Elliott, PhD, Sirtris Senior Vice President of Development. "As we target SIRT1, a gene tied to the aging process and improved mitochondrial function, we hope to develop new therapies for diseases like MELAS and type 2 diabetes".

"We are extremely pleased to have received orphan-drug designation in MELAS," says Christoph Westphal, MD, PhD, CEO and Vice Chair, Sirtris Pharmaceuticals, Inc. "Clinical testing with SRT501 in this mitochondrial disorder offers the potential to provide an exciting, novel treatment option for the future."

MELAS is a progressive and fatal disorder with no known treatments. The earliest symptoms include muscle weakness, fatigue, recurrent headaches and seizures. The reported age of onset varies between 3 and 40 years, with most patients presenting between the ages of 5 to 15 years. The syndrome can manifest as stroke-like episodes in patients under 20 years of age. Seizures, dementia, impaired muscular function and neurodegeneration can be observed as the disease progresses. MELAS patients also have high glucose levels and approximately 30 per cent have type 2 diabetes.

MELAS is caused by a point mutation in mitochondrial DNA, leading to the development of poorly functioning mitochondria, which supply cellular energy. The diagnosis can be confirmed through genetic testing.

In preclinical testing, activation of the SIRT1 enzyme with SRT501 has been shown to increase the number and function of mitochondria. SRT501 has also been shown to be safe and well-tolerated in two earlier human Phase 1a clinical trials. In a phase 1b clinical trial with type 2 diabetes patients naive to treatment, SRT501 was shown to be safe and to significantly lower glucose at the two-hour time point in an oral glucose tolerance test conducted as part of the 28 day trial.

The Phase 1b trial for MELAS conducted at Newcastle University is designed to test the primary endpoints of safety and pharmacokinetics of SRT501 in patients with MELAS. SRT501 is being administered to a group of 15 patients once daily for three months and an additional group of five patients will receive a placebo. Secondary endpoints include exercise tolerance, and fasting blood glucose and insulin levels. Sirtris expects data from this trial in the first half of 2009.

The United States Orphan Drug Act of 1983 was created to provide incentives for companies to develop and market treatments for diseases affecting fewer than 200,000 people in the United States. Under the Orphan Drug Act, more than 300 new drugs have been developed and approved.

Sirtris plans to seek orphan drug status for SRT501 in Europe.

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.