MDA-supported researchers have found that experimental anti-cancer drugs that block IAP genes and kill cancer cells seem to have the opposite effect on muscle generation
Experimental anti-cancer drugs that block IAP (inhibitor of apoptosis) genes and kill cancer cells have unexpectedly been found to induce the growth and repair of muscle tissue, say scientists supported in part by MDA.
The results suggest that these drugs, which are already in clinical trials in cancer patients, might be effective in combating muscle degeneration in conditions like Duchenne muscular dystrophy (DMD) and perhaps other muscular dystrophies. The muscle-related experiments were conducted in cells taken from laboratory mice.
The research team, headed by MDA grantee Robert Korneluk at the University of Ottawa and Children's Hospital of Eastern Ontario, published its findings Oct. 16, 2012, in the journal Science Signaling.
The investigators also found that a naturally occurring protein called TWEAK (TNF-like weak inducer of apoptosis) likewise promotes muscle growth and repair, via the same pathway as the anti-cancer drugs. The TWEAK findings shed additional light on the mechanisms underlying muscle growth and repair, and could provide researchers with additional leads toward therapies.
Specifically, the anti-IAP drugs and the TWEAK protein enhance the fusion of muscle precursor cells called myoblasts into myotubes, which are early-stage muscle fibers. Myoblast fusion is an essential step in the formation and regeneration of muscle.
"We know of five pharmaceutical companies pursuing phase 1 clinical trials with specific [IAP-targeting] drugs to treat cancer patients," Korneluk said in an Oct. 16 press release from Children's Hospital of Eastern Ontario (CHEO).
Eric LaCasse, a study author at CHEO, added that he thought the IAP-targeting drugs could be tried in a muscle disease soon. "We think it's reasonable to move into clinical trials with this methodology within the next couple of years," he said. "Regulatory bodies need proof that the drug is safe, which the existing cancer trials will offer, and they need to see an evidence-based rationale — which we've worked hard to be able to announce today."
MDA is exploring several strategies to fight muscle degeneration, including blocking a protein called myostatin, increasing blood flow to exercising muscles, and developing anti-inflammatory compounds that mimic the benefits but not the side effects of corticosteroids like prednisone.
For an in-depth discussion of the strategies designed to fight muscle-fiber fragility and treat muscular dystrophy, see In Focus: Preserving and Building Muscle Fibers, Quest, April 2011.