Fat-Burning Roche Medicine Stops Diabetes in Mice Study, Researchers Say
One injection of an experimental fat-burning drug from Roche Holding AG (ROG) normalized diabetes in mice for more than a week and helped them lose weight, researchers said.
The medicine may activate a rare type of fat that helps the body keep warm, according to the results published in Science Translational Medicine. The company-sponsored research suggests that treatments aimed at the so-called brown fat may be able to combat obesity-related diseases in a new way. The compound increased energy expenditure and lowered fat levels in the liver in addition to lowering blood sugar, the study said.
“This is an unprecedented effect,” said Junichiro Sonoda, a molecular biologist at the Basel, Switzerland-based company who led the research. “I have never seen anything like this before.” The drug modifies the disease state and removes liver fat so that “the body remains in better shape.”
While most fat stores energy, the brown kind burns it to help keep the body warm. It was thought to be found only in babies until 2009, when three groups of researchers showed that there were small amounts in adults, according to studies published in the New England Journal of Medicine. Brown fat is found in the neck and shoulder blades, and along the spine.
The finding triggered a surge of interest in finding ways to activate the fat, C. Ronald Kahn, an endocrinologist at the Joslin Diabetes Center in Boston, said in a telephone interview. “There is a growing interest in the business world,” said Kahn, who was part of one of research groups two years ago.
“If we can get people to have better activation of brown fat they might burn off more calories, and this would be beneficial in the long run to produce weight loss,” said Kahn, who co-authored a commentary accompanying the Roche study. Kahn is a co-founder of a company focused on brown fat biology that is backed by Boston-based venture capital firm Third Rock Ventures.
One hormone that stimulates brown fat is called FGF21, Kahn said. In 2005, researchers at Eli Lilly & Co. (LLY) published results that showed the hormone normalized blood sugar levels in diabetic mice and reduced fatty particles in the blood called triglycerides.
“A lot of companies tried to make recombinant FGF21 as a drug,” said Sonoda, who works at Roche’s Genentech unit in South San Francisco. The compound cleared from the bloodstream within a couple of hours, however, making it impractical as a treatment, he said.
The Roche researchers made antibodies that would bind to receptors that receive signals from FGF21, including one called FGFR1. Unlike most antibody drugs used to fight cancer, which block incoming growth signals, these antibodies work to stimulate the receptors and thus mimic the effects of the FGF21 hormone.
The effect in mice was better than the Roche scientists anticipated, Sonoda said.
In the study, one injection reduced blood sugar in diabetic mice for 30 days, while also helping mice shed about 10 percent of their weight, Sonoda said. The drug didn’t reduce blood sugar too much, a potential side effect of treatments such as insulin, he said. The antibody boosted the expression of many genes involved in energy expenditure, he said.
“It produces a very sustained effect,” Kahn said. “This is working by a completely different mechanism” from existing drugs.
Almost 26 million Americans have diabetes, according to the American Diabetes Association.
Sonoda said it would take “many years” for a drug based on the research to reach the market. He declined to comment on when Roche might bring the drug into human trials. Three stages of testing are generally required for approval.
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