OTTAWA, ONTARIO--A team of researchers from the Centre de recherche du Centre Hospitalier de l'Universite Laval (CRCHUL) in Quebec City have been successful in developing a technique for neutralizing the gene implicated in Myotonic Muscular Dystrophy (or Steinert's disease). The team is headed by Dr. Jack Puymirat, professor at the Department of Medecine, Faculty of Medecine at Universite Laval, and also a neurologist at CHUL hospital and at the Institut de readaptation en deficience physique de Quebec (IRDPQ). The technique devised by these Quebec researchers also allows them to restore the functionality of dystrophic cells to a normal level. For the first time, this discovery suggests that there is hope to find a treatment for patients who suffer from this disease. This research was funded through the Neuromuscular Research Partnership, an initiative of the Amyotrophic Lateral Sclerosis Society of Canada (ALS) and the Muscular Dystrophy Association of Canada (MDAC) supported by the Canadian Institutes of Health Research (CIHR).

Myotonic Muscular Dystrophy (MMD) is characterized primarily by progressive muscle weakness and muscle wasting by myotonia (difficulty in relaxing a muscle or a group of muscles following contraction). It is a multi-system disease, typically involving a wide range of other tissues as well as muscle. It is the most common of the adult muscular dystrophies. MMD is a disease with dominant transmission, where only one of two genes is abnormal and causes predominant effects of the disease. The appropriate gene therapy consists of neutralizing the gene carrying the abnormality while preserving the normal gene. No gene therapy has yet been discovered to treat diseases with dominant transmission. Research carried out by Dr. Puymirat's team demonstrates for the first time that coming up with an appropriate treatment for this type of disease is a genuine possibility.

Researchers have already undertaken the next step, which consists of verifying if this technique can correct muscular problems in a dystrophic mouse. The results of this step should be available by the end of this year.

"If these results are positive, as we believe they will be, we should be able to launch the first trials of gene therapy on our patients within three to five years," said Dr. Puymirat.

"This research is a major advance in understanding muscular dystrophy," said Dr. Alan Bernstein, President of the Canadian Institutes of Health Research. "It provides a strong foundation to build further advances in the treatment of this disease and is the latest example of the outstanding contributions being made by Canadian health researchers in dealing with the treatment of disease that affects Canadians and people everywhere."

Until now, most research projects on gene therapies have dealt with the development of treatments for muscular dystrophies with recessive transmission. With recessive myotonic muscular dystrophy, the two inherited genes (one coming from the father and the other one from the mother) both carry the abnormality. As opposed to diseases with dominant transmission, the appropriate type of gene therapy in this case is based on the reintroduction of the normal gene.

"The work of Dr. Puymirat and his team is a significant advance in the field of gene therapy. The team has demonstrated, in a cellular model, that their approach can work in muscle cells from persons with myotonic dystrophy. Their findings are an important step in the development of effective gene therapy for myotonic muscular dystrophy and other neuromuscular disorders", said Yves Savoie, National Executive Director of Muscular Dystrophy Association of Canada and Chair of the Institute of Genetics Voluntary Health Organization Working Group.

The technology developed by Dr. Puymirat has already been successful during its first laboratory step on human cells from patients with MMD. Thanks to the innovative use of already known, very powerful tools, such as anti-sense ribonucleic acids (a type of nucleic acids using hereditary information in order to synthesize proteins) and ribozymes (ribonucleic acids with enzyme properties), researchers have succeeded in neutralizing 60 to 80 per cent of the abnormal genes responsible for MMD.

"Besides having managed to neutralize the abnormal gene, we have preserved the healthy gene and restored the cell's normal function. This success allows us to increase the cell's capacity to produce muscular fibres. Once restored, the cell can then uptake glucose, an essential element which allows it to produce more energy," added Dr. Puymirat.

Two prestigious scientific publications (Gene Therapy and Molecular Therapy) have just published simultaneously the results of Dr. Puymirat's research, an event which is extremely rare in the area of human health research.

For more information on Dr. Puymirat and his team's work, please visit: www.crchul.ulaval.ca/crchul/en/acti/Unite/genetique.htm

FOR FURTHER INFORMATION PLEASE CONTACT:

Canadian Institutes of Health Research
Janet Weichel McKenzie
Media specialist
(613) 941-4563
jweichel@irsc.gc.ca
or
ALS Society of Canada
Susan Graham Walker
Director of Communications & Programs
(416) 497-2267, ext. 208
sgw@als.ca
or
Muscular Dystrophy Association of Canada
George Henderson
Communications Manager
(416) 488-2699, ext. 158
ghenderson@mdac.ca
or
Universite Laval
Marielle Morissette
Communications Officer
(418) 656-2131, ext. 4674
marielle.morissette@scom.ulaval.ca