MDA Researchers Treat Cause of Myotonic Dystrophy in Mice

QUEBEC, Oct. 19, 2005 – A multinational team that included MDA grantee Jack Puymirat of Laval University in Quebec targeted toxic genetic information that causes myotonic muscular dystrophy in mice with the disease, using two new molecular techniques, the Muscular Dystrophy Association announced today.

The experimental treatment could be tried in humans in about three years.

The two technique the researchers used are aimed at breaking up or destroying specific strands of RNA, and they both represent a potentially effective approach to treating certain types of genetic diseases in which the presence, rather than the absence, of genetic information is the underlying cause.

“This is the first hint we’ve had of a potentially definitive treatment for myotonic dystrophy,” said Puymirat, a physician and genetics researcher, adding that he hopes to test at least one of the molecular strategies in humans in three to four years.

He described the mouse experiments today in Quebec, at a press conference in conjunction with the fifth biannual meeting of the International Myotonic Dystrophy Consortium.

Type 1 myotonic dystrophy affects one in 10,000 people in most countries and one in 500 people in certain regions of the province of Quebec. It’s a multisystem disease that varies in severity. It usually begins in childhood or adolescence, causes weakness and an inability to relax muscles at will (myotonia), gastrointestinal abnormalities, cardiac rhythm disturbances, cataracts, endocrine abnormalities, and in some cases, cognitive deficits.

In 1992, an international research team supported by MDA identified the cause of type 1 myotonic dystrophy as an expanded section of DNA on chromosome 19. Subsequent work revealed that elongated strands of RNA, produced from the expanded DNA template, become trapped in the nuclei of muscle and other cells, where they stick to and interfere with cellular proteins. More recently, MDA-supported researchers found that the cause of type 2 myotonic dystrophy is a similar DNA expansion on chromosome 3.

Drug treatments can relieve myotonia, pacemaker-defibrillators can regulate the heartbeat, and surgery can treat the cataracts, but there is so far no definitive treatment for the muscle weakness and other systemic features of either form of the disease.

In one set of mouse experiments, Puymirat and colleagues administered the gene for a “ribozyme,” a molecular scissors that can cut targeted RNA strands into small pieces, into the muscles of the dystrophy-affected mice. The gene was encased in a viral delivery vehicle known as AAV.

In another set of experiments, the team inserted a type of blocking RNA called “antisense,” which homes to, sticks to and labels for destruction specific RNA strands.