ANN ARBOR Researchers at the University of Michigan's Life Sciences Institute have found that amlexanox, an off-patent drug currently prescribed for the treatment of asthma and other uses, also reverses obesity, diabetes and fatty liver in mice.
The findings from the lab of Alan Saltiel, the Mary Sue Coleman director of the Life Sciences Institute, are scheduled to be published online Feb. 10 in the journal Nature Medicine.
"One of the reasons that diets are so ineffective in producing weight loss for some people is that their bodies adjust to the reduced calories by also reducing their metabolism, so that they are 'defending' their body weight," Saltiel said. "Amlexanox seems to tweak the metabolic response to excessive calorie storage in mice."
Different formulations of amlexanox are currently prescribed to treat asthma in Japan and canker sores in the United States. Saltiel is teaming up with clinical-trial specialists at U-M to test whether amlexanox will be useful for treating obesity and diabetes in humans. He is also working with medicinal chemists at U-M to develop a new compound based on the drug that optimizes its formula.
The study appears to confirm and extend the notion that the genes IKKE and TBK1 play a crucial role for maintaining metabolic balance, a discovery published by the Saltiel lab in 2009 in the journal Cell.
"Amlexanox appears to work in mice by inhibiting two genesIKKE and TBK1that we think together act as a sort of brake on metabolism," Saltiel said. "By releasing the brake, amlexanox seems to free the metabolic system to burn more, and possibly store less, energy."
Using high-throughput chemical screening at LSI's Center for Chemical Genomics to search for compounds that inhibit IKKE and TBK1, the researchers hit upon an approved off-patent drug: amlexanox. They then demonstrated that amlexanox had profound beneficial effects in both genetic and dietary-induce
|Contact: Laura J. Williams|
University of Michigan