This page contains information and support for people with Myotonic Dystrophy in Canada.
Canada is a country with a centralized medical system. There is additional support for people with myotonic dystrophy in Quebec, as there is a high incidence of Myotonic Dystrophy in this Country. There is also a center for Congential Myotonic Dystrophy research and Dr. Craig Campbell is an expert in this disease. His contact information is at the end of this post.
National Center for Myotonic Dystrophy Opens in Canada The William Singeris National Centre for Myotonic Dystrophy (Dec 2004)
The Muscular Dystrophy Association of Canada can be very helpful. Here is their link: http://www.mdac.ca/
http://users.auracom.com/smdi/muscular.htm (other links)
Dr. Jack Puymirat
The Promise of Gene Therapies for Muscular Dystrophies
Cataracts, muscle weakness in the hands, feet, and face, and a decreasing ability to relax contracted muscles are among the symptoms of myotonic dystrophy, which hits one in every 500 people in Qu?bec.
The clinical aspects of Dr. Puymirat’s work include genetic testing and diagnostics, patient care, data collection, clinical trials, and international collaborations to further define the clinical history and characteristics of myotonic dystrophy. “We are working on the development of a European network to compare phenotype,” says Dr. Puymirat, explaining that the muscular dystrophies in Canada have different features due to the genetic isolation, called a founder effect, that resulted when Europeans settled in Québec. “We hope to look at 2000 families.”
In his research, Dr. Puymirat focuses on the development of gene therapies for the treatment of myotonic dystrophy with the help of funding through the Neuromuscular Research Partnership program. His approach suppresses the expression of the defective gene while maintaining expression of the normal gene.
“Until now, we did not know exactly how the mutation caused the disease,” says Dr. Puymirat. “Now there is some evidence that the mutation causes an accumulation of mRNA in the nuclei.”
Messenger RNA (mRNA) normally carries the transcribed DNA message across the nuclear membrane into the cell’s cytoplasm where it can be translated into proteins for cellular functions. But in myotonic dystrophy, the mutated form of mRNA cannot pass through the nuclear membrane, so it accumulates in the nucleus. Studies suggest that reduced protein function does not play a role in the disease, but the accumulation of the mutant mRNA in the nucleus can.
“If we inhibit the expression of the protein in mice, there is no muscle defect,” says Dr. Puymirat. “But we know the accumulated mRNA binds some nuclear protein and this protein is normally involved in mRNA splicing, in the maturation of mRNA, so the consequence is that the expression of some genes is altered because they are not processed normally.”
Among those affected are genes that code for insulin receptors and chloride channels. “And these channels are involved in myotonia,” says Dr. Puymirat. The effects include insulin resistance, and developing muscle cells (myoblasts) do not fuse together as they should.
“If we want to develop a gene therapy for this disease, we have to destroy this mutant mRNA,” says Dr. Puymirat. One approach is to use antisense RNA to activate specific enzymes that destroy the mutant mRNA.
“Using this approach, we have destroyed about 80 per cent of the mutant mRNA in human myoblasts in vitro,” says Dr. Puymirat. The effect is enough to restore normal myoblast fusion and the effect of insulin.
The research is very promising, but the challenge now is to test it further, using a modified virus as a vector to deliver the antisense RNA to a live animal. “We want to inject mice with AAV (adeno-associated virus) or a lentivirus to see if the antisense will restore function. Then the next step will be clinical trials in patients.”
And the possibilities do not end there. “Another approach we are using is ribozymes,” says Dr. Puymirat. “Ribozymes are small RNA sequences which have catalytic activities. They can cleave any mRNA with a specific sequence.” In the first ever demonstration of the use of ribozymes in myotonic dystrophy, Dr. Puymirat has found a way to target the ribozymes to the mutant mRNA and reduce its levels by 60 per cent. “I think the ribozymes are the most promising approach,” he says.
Dr. Puymirat is not alone in the fight to develop effective new therapies for muscular dystrophies. He and Dr. Jacques Tremblay share a lab at the CHUL and work together on the transplantation of myoblasts as another potential therapy for restoring muscle function. “Dr. Tremblay is doing a clinical trial in muscular dystrophy, and if it works, perhaps we will favour that approach in myotonic dystrophy also,” says Dr. Puymirat.
Adding to the excitement in the lab, Dr. Puymirat’s team had a recent breakthrough in which they discovered the expression of another gene associated with the disease. This is very good news, says Dr. Puymirat, because a drug already exists which may act as an effective antagonist for the gene.
Craig Campbell MD, MSc, FRCPC
Dr. Campbell joined the Department of Pediatrics and Clinical Neurological sciences at the CHWO in 2003 following fellowship training at the University of Ottawa. Dr. Campbell has Canadian certification in electromyography (EMG) and neurophysiology, and runs the pediatric EMG/NCS clinic at the CHWO. In addition to this specialty clinic he also is the medical director of the Neuromuscular and Cerebral Palsy clinics.
Dr. Campbell has recently completed his Masters of Science in Community Medicine and Epidemiology, is an Associate Scientist at the Child Health Research Institute and an Assistant Professor at the University of Western Ontario. His research interests include neuromuscular disease in children and cerebral palsy. He is the director of the William Singeris National Centre for Myotonic Dystrophy Research, which is conducting a Canadian study examining health outcomes in children with congenital myotonic dystrophy. Dr. Campbell is an expert in Myotonic Dystrophy