Obscure Asthma Drug Has Potential for Obesity Treatment

A recent study in Nature Medicine found that a relatively unknown medication for asthma reverses obesity, diabetes, and fatty liver in mice. Amlexanox is a 25-year-old drug used for asthma in Japan and as a paste for canker sores in the U.S. Interest in amlexanox for obesity treatment stems from its inhibition of two genes, IKKE and TBK1, that may play an important role in obesity and diabetes. In obese mice amlexanox stimulated increased energy expenditure through increased basal metabolism. The result was weight loss and improved insulin sensitivity.

Drugs effective in mice are often not useful in humans, but the fact that amlexanox has considerable evidence of safety in humans suggests it might be a candidate for clinical evaluation in the treatment of obesity and related disorders. Dr. George Bray, chief of the Division of Clinical Obesity and Metabolism at LSU’s Pennington Biomedical Research Center, told CNN, “It is a tour de force and offers a new and potentially exciting opening for developments of new anti-obesity drugs — something which is badly needed.”

What led to this remarkable finding? Researchers at the University of Michigan’s Life Sciences Institute led by Dr. Alan Saltiel were looking for compounds that inhibit the IKKE and TBK1 genes, and using high-throughput chemical screening they discovered that the off-patent amlexanox had such properties. In their study in Nature Medicine, the researchers found that amlexanox constrains those genes in mice in the same manner found in the chemical screening, and this drug had profoundly useful effects in both genetic and dietary-induced obese mice. Injected with this medication, the mice lost weight and improved insulin sensitivity, and when they were taken off the drug, the mice gained all the weight back.

The researchers, however, do not yet know if humans respond with the same pathway, or if the discovery of amlexanox effectiveness in mice can lead to a medication that is safe and effective for treating obesity and diabetes in humans. Clinical trials are expected to begin later this year at the University of Michigan to test the drug’s effectiveness in humans. A concern that will need to be examined is whether amlexanox — by increasing metabolism, energy expenditure, and body temperature — might have unintended consequences on other body systems such as the heart.

Click here to read more in Insciences, here to read more from CNN.com, and here to access the study in Nature Medicine.

Lab Mice image © Aaron Logan / Wikimedia