A drug used to treat canker sores and asthma helped lower the weight of obese mice without diet or exercise.
The drug, known as amlexanox, was also able to reverse their diabetes and fatty liver.
Researchers at the University of Michigan’s Life Sciences Institute analyzed the mice in the lab of Alan Saltiel, the Mary Sue Coleman director of the Life Sciences Institute. The findings are published in the journal Nature Medicine.
“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. Amlexanox seems to tweak the metabolic response to excessive calorie storage in mice.”
Using different formulations, amlexanox is used for canker sores in the United States and to treat asthma in Japan. The medication has been sold in Japan for over 25 years.
Saltiel is working with clinical-trial experts at the University of Michigan to examine whether the drug will be an effective treatment for obesity and diabetes in people.
He and medicinal chemists at the University are also trying to create a novel compound based on the drug that makes the best use of its formula.
The research supports a previous study in the Satiel lab, published in the journal Cell, that metabolic balance is maintained with the critical help from the genes IKKE and TBK1.
“Amlexanox appears to work in mice by inhibiting two genes – IKKE and TBK1 – that we think together act as a sort of brake on metabolism,” Saltiel revealed. “By releasing the brake, amlexanox seems to free the metabolic system to burn more, and possibly store less, energy.”
The scientists came upon amlexanox at LSI’s Center for Chemical Genomics after looking for compounds that inhibit the two genes using high-throughput chemical screening.
The researchers discovered that the drug was notably beneficial for both genetic and dietary-induced obese mice.
The weight of the obese animals was reduced by the chemical, and associated metabolic issues, including diabetes and fatty liver, were reversed.
“These studies tell us that, at least in mice, the IKKE/TBK1 pathway plays an important role in defending body weight by increasing storage and decreasing burning of calories, and that by inhibiting that pathway with a compound, we can increase metabolism and induce weight loss, reverse diabetes and reduce fatty liver.”
The experts do not yet know whether humans react with the same pathway, or whether the results of amlexanox, which works in mice, can result in the development of a compound that is safe and advantageous for people.
“We will be working hard on that,” Saltiel said.
The obesity drug Lorcaserin received a positive vote from FDA (Food and Drug Administration) Panel last year. Lorcaserin is intended for obese and overweight people to manage their weight, including weight loss and staying at a healthy weight.
Written by Sarah Glynn