Friday, September 5, 2008

Dana Farber researcher makes ‘bad’ fat ‘good’

By Stephen DeSantis

A Dana Farber Cancer Institute researcher could be leading the way down a whole new road in treating obesity. It turns out that fat cells have a benevolent twin brother, researchers say. In fact, these “good” fat cells, called brown fat, help to burn away those troublesome white fat cells that store our unused calories.

Research published last month by Bruce Spiegelman, a Dana Farber investigator and a professor of cell biology at Harvard Medical School, indicates that a commercial application using brown fat may not be far off.

Spiegelman’s research has been instrumental in finding ways to create brown fat; in this latest case using a gene that acts as a “molecular switch” called PRDM16.

Last year Spiegelman’s research team inserted PRDM16 genes into regular fat cells and converted them into good, calorie-burning fat. Spiegelman’s newest discovery is even more promising, he said, because it can be used to make brown fat from muscle cells that have not fully formed yet.

He stressed that although there are surgical and lifestyle approaches in treating obesity, the need is still high for a medical alternative. His lab has already filed patents on the use of this approach.

“I believe in the idea. It’s an idea that could form the flagship of a new company. I’m positive about that. I’m in discussion with a number of VCs and if the right pieces fall into play, I’m interested,” he said.

The market for anti-obesity treatments rose from $800 million in 2000 to a predicted $3 billion in 2008, according to the London-based market research firm Datamonitor Ltd. Obesity has been linked to myriad diseases, including Type 2 diabetes, heart disease and even cancer.

A number of local biotechs have tried their hand in the obesity market with mixed results. Peptimmune Inc., for example, tried to develop a system that blocks the absorption of fats. The program ultimately failed and the Cambridge-based company has since exited the obesity area. Also in Cambridge, Syndexa Pharmaceuticals Corp. is developing a drug to treat metabolic disorders by targeting inflammatory-metabolic signaling.

Spiegelman’s research would be a novel approach in tackling obesity.

“I certainly think his (Spiegelman’s) recent discovery around the development of brown fat is really one of the top basic research breakthroughs in adipose (fat metabolism) biology within the last few years,” said Lou Tartaglia, a partner at Third Rock Ventures.

Tartaglia is Third Rock’s specialist in the field of obesity and metabolism. Tartaglia was instrumental in Third Rock’s funding of the obesity-focused Boston-based biotech Zafgen Inc.

But Spiegelman may soon have competitors in the brown fat race. A similar, although independent, study on brown fat was performed at the Joslin Diabetes Center and was published in the same Aug. 21 issue of the journal Nature. That group, led by Yu-Hua Tseng, found that mice that were injected with different a protein, known as BMP-7, made more brown fat and gained less weight than normal mice.

Spiegelman’s research team is now collaborating with the Broad Institute of MIT and Harvard in order to try and find chemical agents that can mimic the PRDM16 gene action — step one in developing a new drug.