Could a 30-year-old asthma drug lead to a new treatment for diabetes?

The anti-inflammatory drug amlexanox was invented in Japan in the 1980s to treat asthma but was quickly eclipsed by more effective treatments. Now a team of scientists led by the University of California at San Diego is looking at repurposing the drug in an entirely new setting: Type 2 diabetes.

The UCSD team, working with scientists at the Salk Institute and the University of Michigan, discovered that two enzymes called IKKε and TBK1 are ratcheted up in obese mice, making it difficult for them to burn calories and expend energy. So they screened 150,000 chemicals in search of something that would inhibit those two enzymes, according to a press release from UCSD. That’s when they stumbled upon amlexanox. They’ve now shown that some people with Type 2 diabetes experience a significant drop in glucose after taking the drug.

The researchers tested amlexanox in 21 people with obesity and Type 2 diabetes, and compared them to a control group given a placebo. A third of people taking the drug responded to it, according to the release. Patients who had nonalcoholic fatty liver disease also responded well to it.

The researchers wanted to understand what separated the responders from the non-responders, so they took biopsies of fat cells from the patients at the beginning and end of the study. They discovered more than 1,100 genetic changes that occurred in people who responded to amlexanox, but that were absent in patients who didn’t respond.

The link to inflammation was also evident in those biopsies. "In the responder group, the level of inflammation in fat was higher than in the non-responder group at the beginning of the study, indicating that there is something about inflammation that predisposes a person to respond,” said Alan Saltiel, Ph.D., director of the UC San Diego Institute for Diabetes and Metabolic Health, in the release. The findings were published in the journal Cell Metabolism.

The UCSD-led project is among many aimed at finding new targets for treating metabolic disorders. Another approach that has been gaining steam lately involves turning unhealthy white fat into brown adipocytes—cells that burn energy and seem to fend off obesity. Last year, scientists at the University of Pennsylvania announced they had identified a signaling pathway that converts white fat to brown fat and might be able to be targeted with drugs.

Inhibiting inflammatory enzymes is an entirely new approach, UCSD’s Saltiel acknowledges, and it raises several challenges that still need to be addressed. His team is now working to figure out which of the thousands of gene changes are most important to address, what the proper dosage of amlexanox should be in people with diabetes and related disorders, and what other drugs might be able to be used in combination with the asthma treatment to make it more effective.

"It's a new mechanism for a diabetes and fatty liver drug,” Saltiel said. “It's promising, but there are a lot of questions that need to be answered still."