New hope from an old drug
by Jennifer Xu
From the April, 2013 issue
A drug developed in Japan in the 1980s could be the long-awaited answer to the obesity epidemic.
The drug, amlexanox, has been found by researchers at the U-M's Life Sciences Institute to be effective in reducing fat deposits and type 2 diabetes in obese mice. But what possessed the group, headed by LSI director Alan Saltiel, to take another look at a drug normally smeared on canker sores or ingested as a tablet for asthma?
The short answer is that the nation is gripped by an obesity epidemic. And rather than hunt for new compounds that could help--but might not be safe for human use--the U-M team screened already-approved drugs looking for one that did what they wanted: "Amlexanox appears to work in mice by inhibiting two genes ... that we think together act as a sort of brake on metabolism," Saltiel announced in a press release. "By releasing the brake, amlexanox seems to free the metabolic system to burn more, and possibly store less, energy."
One-third of all American adults are considered overweight, and another third clinically obese. Obese people live shorter lives, and the quality of life they do live is plagued with diseases, among them type 2 diabetes, chronic heart disease, stroke, and cancer. But, as any dieter can tell you, it's not easy to shed the extra pounds. Despite attempts to improve nutrition and exercise more, dieters often hit a wall in their weight-loss efforts. That's because when we get less food, our metabolisms slow down to account for the decreased caloric intake. The less food we consume, the fewer calories our bodies will want to burn.
The U-M study, published in the journal Nature Medicine in February, suggests that amlexanox may offer a way around that problem. The researchers discovered that two separate populations of obese mice lost weight after being injected with the drug. The mice also had improved glucose tolerance (a sign of decreased diabetes) and produced less fatty tissue in their livers.
significantly, the drug didn't reduce the animals' food intake. Though the obese mice continued to gorge themselves on food, they still lost a considerable amount of weight.
Though the amlexanox-injected mice didn't stop overeating, they were much more active than those who didn't have exposure to the drug. Normally, the fatter you are, the less you move. But as the U-M team hoped, the amlexanox mice had metabolisms comparable to mice with a much lower weight, dissipating the extra energy in their fat cells as heat.
So far, the experiments have been performed only on laboratory mice, so the researchers have been hesitant to draw any conclusions about the drug's effectiveness on obese human patients. But since amlexanox has been safely used in Japan for the past twenty-five years and its patent has expired, clinical trials can begin immediately, without the high cost and delay involved in licensing an existing drug or winning approval for a new one.
Despite amlexanox's promise, at a U-M talk in February Saltiel expressed concern that the national budget sequestration that went into effect March 1 will impact future studies on the drug. Much of the university's biomedical research is funded by the National Institutes of Health, and the sequester trims NIH's $31 billion budget by $1.5 billion. Saltiel is seeking other funding to begin human studies.
[Originally published in April, 2013.]