Canadian Corporate News
02/18/04, 1:30p
(Copyright © 2004, Canadian Corporate News)

OTTAWA, ONTARIO--The results of the first clinical trial on three people from Quebec affected by Duchenne Muscular Dystrophy raise the possibility of a treatment for this debilitating disease. A Quebec research team, directed by Dr. Jacques-P. Tremblay of the CHUL Research Centre, part of the Centre hospitalier universitaire de Quebec, has developed an experimental treatment based on the transplantation of cells called myoblasts. These cells are obtained from a close relative donor and grafted in a muscle of those affected by Duchenne Muscular Dystrophy. When the myoblasts fuse with existing muscle fibres, they introduce the normal dystrophin gene in these fibres.

Muscular dystrophy is a group of hereditary diseases characterized by a progressive muscle weakness. One of them, Duchenne Muscular Dystrophy (DMD), affects one boy out of 3,500. There is currently no treatment for this disease. Dr Tremblay's team is the only one worldwide to develop a treatment.

The first clinical trials are positive. Dystrophin is a protein that is absent in people with Duchenne Muscular Dystrophy. However, one month after an injection of healthy myoblasts obtained from a close relative, dystrophin was detected. The success of this cell transplantation depends on adequate immunosupression with a new drug called Tacrolimus; injection of a high number of cells (30 million/cm3); and a short distance between injection trajectories. The results of these first tests have just been published in Molecular Therapy, the journal of the American Society for Gene Therapy.

"We are very happy with these promising results. For the first time in the world, we have succeeded in recreating muscle fibres expressing dystrophin in several patients. This first phase of our research work opens the way to a potential treatment," explained Dr. Tremblay.

"This work is a new and very promising beginning for the treatment of a devastating genetic disease," said Roderick McInnes, Scientific Director of the Institute of Genetics of the Canadian Institutes of Health Research (CIHR).

"This breakthrough is an excellent example of how collaboration between multiple funding partners can propel research from identification of the genetic basis of disease toward potential therapies," added Teren Clarke, Chair of CIHR's Institute of Genetics Voluntary Health Organizations Working Group and National Director, Programs and Services, Muscular Dystrophy Canada.

The first phase of this clinical trial consisted of 25 injections of healthy cells in one cm3 of muscle of a patient affected by the Duchenne Muscular Dystrophy. The next phase of this research project will be to inject healthy cells throughout a whole muscle using several hundred injections, to verify whether the technique may increase the strength of the muscle.

"We have just received permission from Health Canada to increase the number of injections from 25 to 100. Phase two of our project will allow us to verify whether our technique can increase the strength of one muscle or at least prevent the progression of the weakness," commented Dr. Tremblay.

Multiple applications

The myoblasts were obtained from a muscle biopsy of a healthy close relative. These cells were then proliferated in culture in a clean room laboratory, the first one approved in Canada for the proliferation of human cells to be injected into patients. These cells were then injected in a small part of the muscle of a patient affected by Duchenne Muscular Dystrophy. A muscle biopsy one month later permitted the researchers to verify whether the healthy cells have generated muscle fibres expressing dystrophin. This technique offers hope not only for patients affected by Duchenne Muscular Dystrophy, but also for all those affected by a dystrophy with a recessive transmission. A few French and American teams are currently working on a similar technique to treat patients with heart disease following damage produced by an infarction.

The clinical trial is supported by a research grant from the Association Francaise contre les Myopathies (AFM) (a foundation located in France) and by a research contract from CellGene Inc., a start-up company created to develop the myoblast transplantation technology. This start-up is incubated by SOVAR, a society created by Laval University and the Centre hospitalier universitaire de Quebec to facilitate the commercialization of discoveries by their investigators. The basic research program that led to Dr. Tremblay's clinical trial is funded jointly by CIHR, Muscular Dystrophy Canada and the ALS Society of Canada through the Neuromuscular Research Partnership. The research is also supported by a number of foundations including the Muscular Dystrophy Association (MDA, United States), the Advanced Research in Myopathy (ARM, United States), l'Association quebecoise de dystrophie musculaire (AQDM) and the Stem Cell Network (a center created by Canada's Networks of Centres of Excellence).