Wednesday, November 26, 2008

Sirtris finds ageing-associated enzymes offer disease protection

By Marc Songini

Researchers at Cambridge-based Sirtris Pharmaceuticals Inc. may have found a potential way to activate the body’s own genetic mechanisms related to ageing to ward off or treat diseases such as cancer, showing for the first time that the body mechanism it is studying works in mammals.

Sirtris believes that there may be a way to use enzymes called sirtuins to prevent DNA injury or repair existing damage that causes diseases. “Certain diseases are due to certain DNA getting damaged,” said Michelle Dipp, Sirtris’ vice president of corporate development. “As we age, there are certain changes, and the gene expression pattern changes, and certain DNA that should be repaired don’t get repaired. We know that directly causes cancer,” she said. 

Sirtris, a subsidiary of U.K.-based GlaxoSmithKline PLC, is focused on developing drugs to treat aging-related diseases. In a study being published today, the scientists unveiled data demonstrating that as a cell’s ability to manage gene expression diminishes, the human body ages. Gene expression is the mechanism by which genes are switched on and off.

Researchers examined sirtuins, a class of enzymes believed to be connected to ageing. They discovered that sirtuins regulate the process of turning genes off as the body ages. Secondly, they also claim that it’s sirtuins’ task to repair damaged DNA. The researchers conducted their studies on a sirtuin called SIRT1, the best known of these enzymes, which is switched on during exercise or dieting. The researchers found that as a body ages, the DNA damage rate increases, and in turn, the SIRT1 enzyme must play a greater role in repairing the DNA.

While scientists have known for almost a decade that SIRT1 repaired DNA and regulated genes in yeast, this is the first time it’s been revealed that it also does so in mammals, the Sirtris researchers found. 

While drugs that are capable of activating SIRT1 currently exist, they are of limited potency, said Dipp. However, Sirtris is already finishing Phase 1 tests with two new SIRT1 activators that have greater power. Sirtris plans to conduct a Phase 2 study early next year using cancer and diabetes patients. “We’re committed to finding drugs that activate SIRT1,” said Dipp. “This gives us confidence we will see benefits.”