FOR IMMEDIATE RELEASE

Discovery could increase effectiveness of important drugs, lengthening and improving the life span of children who suffer from the incurable condition.

October 1, 2004 - About 20 years ago, scientists stumbled upon a treatment that seemed to have beneficial effects on children suffering from muscular dystrophy. At the time, doctors were unsure why glucocorticoid drugs, which were traditionally used to treat inflammations, had an impact on muscular dystrophy, they simply noted the results.

Twenty years later, glucocorticoid treatments are still the only effective treatment against muscular dystrophy. Until now, no one was really sure how the drugs worked against the incurable condition - thereby diminishing the likelihood of improving its efficiency.

That mystery has now been solved.

Dr. Lynn Megeney, a senior scientist at the Ottawa Hospital Research Institute (OHRI) and Dr. Bernard Jasmin, a Professor and Chair of the Department of Cellular and Molecular Medicine at the University of Ottawa, have discovered that glucocorticoid treatment alleviates the symptoms of muscular dystrophy by countering the devastating effects of a specific biochemical pathway in muscle fibres.

Understanding the pathway

The fundamental problem in Duchenne muscular dystrophy is a gene defect that results in the absence of the muscle protein dystrophin. In 2002, Dr. Megeney's group discovered that in the absence of dystrophin, an important series of biochemical reactions in muscle fibres is triggered, resulting in the eventual destruction of muscle fibres. The collaborative study with Dr. Jasmin's group has now shown that glucorticoids act to counter the effects of this overly active pathway.

For people who suffer from muscular dystrophy, glucorticoid treatment translates into improved mobility and a longer life. Unfortunately, glucorticoid also have negative side effects such as weight gain and bone loss and in time, the side effects are sufficiently pronounced to often stop treatments.

By finally understanding why and how the drugs work, Drs. Megeney and Jasmin are opening the door to a series of promising possibilities. For instance, it is now possible to improve the drug by targeting the aspects that make it work. By the same token, scientists can focus on the positive elements and try to reduce the negative.

"This is a stunning revelation that I believe will have important consequences for the improvement of the only treatment available for muscular dystrophy," said Dr. Ronald Worton, CEO and Scientific Director of the OHRI. Dr. Worton is also the scientist who discovered the gene defect in Duchenne muscular dystrophy in 1986. "I have waited 18 years for this understanding and congratulate the two research teams on their important achievement."

The discovery is being published on October 1st in the Federation of American Societies of Experimental Biology.

"We are hoping that with this discovery, we can turn muscular dystrophy into a condition that is treatable, like Type 1 Diabetes," explained Dr. Lynn Megeney, who is also an assistant professor in the department of Cellular Molecular Medicine at the University of Ottawa and a founding scientist of StemPath Inc. a biotechnology company. "This may not be a cure but with time and more research, it might give children suffering from muscular dystrophy a hope at a normal life span."

"The discovery of this specific pathway now provides a unique opportunity for the rational design and development of additional and more effective drugs to slow and counter act the relentless progression of this devastating neuromuscular disease, noted Dr. Jasmin. "A major advantage of drug treatment over other avenues, is the systemic nature of this approach which could provide children with therapeutics that act throughout the musculature."

"This is the latest in a long series of major achievements in the area of neuromuscular diseases that have come from University of Ottawa researchers," said Dr. Peter Walker, Dean of the University of Ottawa Faculty of Medicine.

The study was funded by the Muscular Dystrophy Association in the United States and carried out by graduate students Simon St. Pierre, Joe Chakkalakal, and Dr. Steve Kolodziejcyk , a post-dcotoral research fellow.

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