2 min readResearch Shows Canker Sore Drug May Aid in Weight Loss

La Jolla, CA – A team of scientists, including researchers from the Salk Institute for Biological Studies, has discovered that a drug used to treat canker sores appears to reverse obesity in mice.

The findings, published February 10 in Nature Medicine, may lead to new weight-loss medications that could have an impact on growing obesity and diabetes rates in the United States. The drug, amlexanox, has been on the market for more than 15 years. Different formulations of the drug are used in Japan to treat asthma and in the United States to treat canker sores. Human clinical trials for weight loss are expected to begin later this year.

“Amlexanox seems to be a relatively safe drug with a long history of use in patients,” says Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory and lead researcher in the Institute’s new Helmsley Center for Genomic Medicine, who participated in the study with researchers from the University of Michigan and the University of California, San Diego. “As such, there might be an interesting opportunity for repurposing this agent for diabetes and obesity.”

The researchers fed mice a high-calorie diet. Once they became obese, the mice were injected with amlexanox. Despite eating the same amount of calories as control mice, the animals injected with amlexanox lost weight. In addition, the drug reduced their body fat and reversed type 2 diabetes and fatty liver that was a result of the mice’s obesity. When the mice were taken off the drug, they gained back all the weight they had lost.

While screening nearly 150,000 drugs, the researchers discovered that amelexanox changed the way the mice’s genes controlled their metabolism. Rather than acting as an appetite suppressant, the drug increased metabolism. Amlexanox appears to inhibit two genes in mice―IKKE and TBK1―which senior author Alan Saltiel of the University of Michigan previously found play a critical role in maintaining metabolic balance. The drug acts as a sort of brake on metabolism. By releasing the brake, amlexanox frees the metabolic system to burn more and store less energy.

“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,” says Saltiel. “Amlexanox seems to tweak the metabolic response to excessive calorie storage in mice.”

To ensure that the drug itself was making the mice lose weight and not something else, the researchers used a laser-based device to see if the mice lost weight because they moved around more while on the drug. Rather, they discovered that a physiological process called thermogenesis, the process of heat production in an organism, increased the mice’s energy expenditure and fat oxidation, leading to the weight loss.

Because amlexanox is already approved by the Food and Drug Administration for canker sores, it could potentially be available for weight loss more quickly than other drugs awaiting approval. First, however, it must be proven safe and effective in weight-loss clinical trials. One concern the researchers have is that by increasing energy expenditure and body temperature, amelexanox may also affect other body systems. And, because the effects of the drug are reversible upon withdrawal, patients may need to stay on the drug indefinitely―or gain back they weight they have lost.

To read the article, see: http://www.nature.com/nm/journal/v19/n3/full/nm.3082.html

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