Merg1a New Front In Atrophy Battle?

Better understanding of muscle atrophy -- the wasting of muscle tissue that occurs in various disease states or when weight bearing doesn’t occur for some time -- may reveal new targets for muscular dystrophy treatment, say researchers at Purdue University in West Lafayette, Ind., and the University of Pittsburgh.

Xun Wang and colleagues, who published their results online May 24 in The FASEB Journal, found that activation of a protein known as Merg1a may be the starting gun that sets off an atrophy program in muscle cells.

When mice that had been prevented from bearing weight on their back legs for seven days were given a drug called astemizole, which blocks Merg1a function, they experienced significantly less atrophy than mice that didn’t get the drug.

Amber Pond and Kevin Hannon at Purdue’s School of Veterinary Medicine, who led the study, said their group has since experimented with mice affected by a disorder resembling Duchenne muscular dystrophy (DMD).

“We have tested mdx [DMD-affected] mice for the Merg1 protein and, cursorily, it appears to be more abundant in the mdx mice than in control mice,” Pond said.

Pond emphasized that astemizole can’t be safely used in humans because of its dangerous effects on cardiac muscle. She noted, however, that in the heart, it’s believed that there are two different Merg1 proteins -- Merg1a and Merg1b -- whereas in skeletal muscle, there’s only Merg1a. That might make it possible, she said, to target the skeletal muscle form without affecting the heart protein.

Pond added that her team’s findings “do not contradict the existing knowledge of atrophy. They do, however, add novel insight into the mechanism by which atrophy is initiated.”