Scientists have designed a drug candidate while experimenting on mice, which significantly increases exercise endurance in animal models.
The findings by an international group of scientists from the Florida campus of The Scripps Research Institute (TSRI) could lead to new approaches to helping people with conditions that acutely limit exercise tolerance, such as obesity, chronic obstructive pulmonary disease (COPD) and congestive heart failure, as well as the decline of muscle capacity associated with aging.
The drug candidate, SR9009, is one of a pair of compounds developed in the laboratory of TSRI Professor Thomas Burris as reducing obesity in animal models. The compounds affect the core biological clock, which synchronizes the rhythm of the body's activity with the 24-hour cycle of day and night.
The compounds work by binding to one of the body's natural molecules called Rev-erba, which influences lipid and glucose metabolism in the liver, the production of fat-storing cells and the response of macrophages (cells that remove dying or dead cells) during inflammation.
In the new study, a team led by scientists at the Institute Pasteur de Lille in France demonstrated that mice lacking Rev-erba had decreased skeletal muscle metabolic activity and running capacity.
Burris' group showed that activation of Rev-erba with SR9009 led to increased metabolic activity in skeletal muscle in both culture and in mice. The treated mice had a 50 percent increase in running capacity, measured by both time and distance.
The authors of the new study suggest that Rev-erba affects muscle cells by promoting both the creation of new mitochondria and the clearance of those mitochondria that are defective.
The study was published July 14, 2013, by the journal Nature Medicine.