Mice Run Farther on a Drug That Mimics Exercise

Mice given a new compound ran longer and farther than mice that did not receive it, and they had never been asked to work out. The experiment comes from the lab of Thomas Burris, a pharmacologist at the University of Florida. His work focuses on diseases that respond to exercise, such as obesity, type 2 diabetes and dementia. The aim is not to replace exercise. It is to bring some of its benefits to people living with frailty, disability or chronic illness.

Exercise builds muscle, strengthens bones, lowers blood pressure and lifts mood. Researchers are now trying to identify the chain of hormones, enzymes and other molecules behind those effects. The mechanism Burris's team has followed starts with a receptor, a protein that relays chemical signals into the cell. In muscle cells this receptor is always switched on, even without exercise. Working out appears to boost it, and that boost helps build endurance over time. Burris's lab has spent years designing a drug that increases the receptor's activity directly. The compound also shows signs in mice of mimicking some cognitive benefits of exercise and of helping with heart failure.

The obstacles are considerable. Scientists must turn that knowledge into drugs that are both safe and effective, and more than 90% of treatments that enter human studies fail. Regulation adds another hurdle: the FDA approves medications to treat diseases, not to enhance wellness, as Burris points out. Some preliminary results have been promising enough that anti-doping authorities have already banned compounds in this family. There may never be a single pill that delivers every benefit of exercise, and the mouse results remain in animals.

Other compounds are further along. In June, the biotech firm Cambrian Bio reported that its experimental drug ATX-304 boosted metabolism and reduced liver and belly fat in people with obesity and prediabetes. The drug activates a metabolic switch that helps cells sense when energy supplies dip and coordinates the production of more fuel, the same switch that helps the body sustain long sessions of jumping rope or swimming laps. Cambrian hopes the drug will help people lose weight without losing muscle, a common concern with GLP-1 medicines, the drugs used for weight loss.

For people with frailty, disability or chronic illness, the gain would be a medicine that carries part of the benefit of movement they cannot easily get. Burris founded Pelagos to move his compound toward a clinical trial, and no date has been announced for that step. Until a compound clears human testing, the change remains a laboratory result.