February 11, 2013
Old Asthma Drug Provides Benefits For Treating Diabetes, Obesity
Lawrence LeBlond for redOrbit.com - Your Universe Online
A drug that is normally prescribed for asthma patients is breathing new life as a potential treatment option for people who suffer from diabetes and obesity. The drug, amlexanox, was demonstrated to reverse obesity, diabetes and fatty liver in mice in a new study, published this week 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," Saltiel said in a statement. "Amlexanox seems to tweak the metabolic response to excessive calorie storage in mice."
With the highly positive results from his mice study now on hand, Saltiel is now teaming up with clinical trial researchers at UMich to test the drug on humans. He said he is also working with medicinal chemists at the school to see if the formula can be optimized.
Saltiel´s mouse study appears to confirm the notion that genes IKKE and TBK1 play a crucial role in maintaining metabolic balance, adding to a discovery in Saltiel´s lab in 2009 that was published in the journal Cell.
"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 maintained. "By releasing the brake, amlexanox seems to free the metabolic system to burn more, and possibly store less, energy."
Saltiel and his colleagues used high-throughput chemical screening at LSI´s Center for Chemical Genomics to track down compounds that inhibit the metabolic-balancing genes. Through this screening process, the team found off-patent amlexanox, which has been on the Japanese market for more than 25 years.
After finding this IKKE/TBK1 gene-inhibiting drug, the team then demonstrated the profound beneficial effects it had on both genetic and dietary-induced obese mice. The drug proved to lower obesity rates in mice and reverse related metabolic problems such as diabetes and fatty liver.
"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," Saltiel said in the statement.
While the implications of such a finding are profound, it is too early to tell if the drug will have similar effects on humans. It is also not known if tweaking the compound/formula will be a safe and effective method for treating diabetes and obesity in humans.
Saltiel´s research was supported by the LSI´s Innovation Partnership, the National Institutes of Health (NIH), the Michigan Diabetes Research and Training Center, the Michigan Institute for Clinical and Health Research (ICHR), and the Nathan Shock Center in the Basic Biology of Aging.