Michigan Medicine and the University of California at San Diego scientists in a collaboration have found that a 30 year old drug- Amlexanox, prescribed in Japan for the treatment of Asthma is effective in the treatment of Type 2 Diabetes, the form caused by obesity.
The drug was previously shown to improve diabetes and weight loss in obese mice by Dr. Alan Saltiel, director of the Institute for Diabetes and Metabolic Health at U-C San Diego, “ “We know that amlexanox works to reverse obesity and insulin resistance in part by resolving chronic inflammation and increasing energy expenditure, but that’s not the whole story of the drug’s effects,” said lead author of the current study, Shannon Reilly, Ph.D.
“Understanding how the drug also enables crosstalk between fat cells and the liver in obese mice allows us to see more of the amlexanox picture, and also sheds light on communication between different tissues in the body.”
Amlexanox is an inhibitor of two enzymes, IKKɛ and TBK1 tha
t caused a drop in energy expenditure or reduction in calories burned; this was revealed in this study using mice which prompted the scientists to further look for inhibitors of these enzymes by screening a library of 150,000 chemicals which is how they rounded on amlexanox.Presently, researchers tested amlexanox for 12 weeks 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.
“When we looked at the drug-treated group we saw a bimodal distribution, that is, there were some responders and some nonresponders. We didn’t understand why, so we did a molecular analysis from biopsies of fat cells we took from patients at the beginning and end of the study,” says Saltiel, And when biopsied, 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, “In the responder group, the level of inflammation in fat was higher than in the nonresponder group at the beginning of the study, indicating that there is something about inflammation that predisposes a person to respond. And, what was really amazing was that there were more than 1,100 gene changes that occurred exclusively in the responders.”
Hence the human trial revealed that gene changes that occurred in the mouse model also happened in the human responder group. Blood sugar in the clinical trial patients went down as genes involved in the expenditure of energy changed.
“The most exciting part of this is that we have a new drug that has never been studied before,” says Saltiel. “It’s a new mechanism for a diabetes and fatty liver drug. It’s promising, but there are a lot of questions that need to be answered still.”
