Third Rock seeds a new approach to treating diabetes and obesity

Boston venture capital group Third Rock Ventures has gathered together several prominent scientists working in the diabetes and obesity fields under the banner of a newly seeded biotech company as it ponders an ambitious new launch.

The fledgling Adipothermics was initially co-founded by Pat Griffins, chairman of the department of molecular therapeutics at Scripps' Florida research campus, where he's been collaborating with Dana-Farber's Bruce Spiegelman, a professor of cell biology at Harvard Medical School, on PPAR gamma. A third scientist, Ron Kahn of the Joslin Diabetes Center in Boston, is contributing his insights on brown fats, which are known to burn up calories.

Spiegelman and Griffins garnered significant attention in scientific circles last fall when they unveiled new research they believe pinpoint the reasons why Avandia and Actos sometimes cause weight gain, the erosion of bone density and water retention among diabetics. While the drugs activate PPAR-gamma, making cells more sensitive to insulin and improving blood sugar, the scientists confirmed just weeks ago that when PPAR-gamma undergoes a process called phosphorylation by the kinase Cdk5, it disrupts various genes. Their new compound, SR1664, tested in mice, provided preclinical confirmation of the science behind a new drug program that blocks the Cdk5 enzyme, eliminating the side effects.

"We established proof of concept that you can dial out the agonism to essentially zero while blocking the phosphorylation event and maintaining efficacy," says Griffins.

"It overlaps and it's a bit technical in terms of how they overlap," says Third Rock partner Lou Tartaglia about the work of Spiegelman and Griffins and Joslin's Kahn. "The projects are also frankly separable. PPAR-gamma acts at the level of insulin resistance while many of the other projects we're putting together act directly in brown fat activation."

The seed stage, which has consumed a couple of million dollars at Third Rock, according to Tartaglia, snugly fits the venture group's model for biotech startups. The VC group brings together leading researchers and cutting-edge science, considers the costs involved and potential rewards, and decides whether the new outfit warrants a significant round in a push toward clinical proof-of-concept data. That go/no go decision, says Tartaglia, should come before the end of the year.

He added that if Third Rock does decide to go ahead with a formal launch, the new company will be based in Boston.

- here's the story from Scripps on the research