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Asthma Drug Reveals Potential as Diabetes, Obesity Treatment

Alan Saltiel (University of Michigan)

Alan Saltiel (University of Michigan)

A drug long prescribed for asthma and canker sores has been shown in tests on mice to reverse obesity and diabetes. Researchers from University of Michigan in Ann Arbor, and labs in California and Australia, published their findings yesterday online in the journal Nature Medicine (paid subscription required).

Alan Saltiel, director of Michigan’s Life Sciences Institute (pictured right), led the Michigan team, with colleagues from University of California in San Diego, Salk Institute for Biological Sciences also in San Diego, and University of Sydney in Australia. The team tested the drug amlexanox, prescribed in different formulations to treat allergic asthma and oral skin ulcers, such as canker sores.

Their investigation began as a search to find ways of inhibiting the genes IKKE and TBK1 that maintain metabolic balance, but also act as a brake on metabolism. “One of the reasons that diets are so ineffective in producing weight loss for some people,” says Saltiel, “is that their bodies adjust to the reduced calories by also reducing their metabolism, so that they are ‘defending’ their body weight.” In 2009, Saltiel’s lab highlighted the role played by the genes IKKE and TBK1 in maintaining metabolic balance.

The Michigan researchers used high-throughput genomic screening at the Life Sciences Institute to identify current drug compounds that inhibit IKKE and TBK1, and the results hit on amlexanox. The drug, for which patents have expired, is made by the Texas company Uluru Inc. in paste form to treat canker sores, and has been prescribed for more than 25 years in in Japan to treat allergic asthma.

The team fed mice a high fat diet to create obesity, but also gave some of the mice amlexanox. The results showed the mice given amlexanox increased their burning of energy, producing weight loss, improved insulin sensitivity, and decreased fatty liver disease known as steatosis. “Amlexanox seems to tweak the metabolic response to excessive calorie storage in mice,” notes Saltiel.

Getting results with animals does not always translate into clinical benefits for humans, however. With support from the Life Science Institute’s Innovation Partnership that provides funding and business mentorship to move research toward commercialization, the team will next examine if humans respond to the same pathway as mice, leading to a compound that is safe and effective for treating obesity and diabetes in humans.

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