The cause of Duchenne muscular dystrophy (DMD), a common, severe form of muscle-wasting disease, was not understood 30 years ago. Young boys diagnosed with DMD, which affects one in 3,500, were fated to gradually lose the ability to walk and to die before they reached their mid-20s. DMD was first described in the 1860s by French neurologist Guillaume Duchenne, who believed electricity would be used to treat the disease.
Diagnosis, said the late Dr. George Karpati, a senior neurologist and neuroscientist at the Montreal Neurological Institute of McGill University, is based on medical examination, a muscle biopsy, a blood test to look for elevated levels of creatine kinase (an enzyme that leaks from damaged muscle tissue) and finding an X chromosome- linked genetic mutation. The genetic association of DMD was recognized in the mid-1970s.
Treatments at the time were physiotherapy, leg braces and wheelchairs, which were directed at the symptoms of DMD and to preventing the involuntary muscle shortening that leads to limb and spinal deformities.
In the last two decades, medical advances have improved therapies for DMD. In the 1980s, assisted intermittent respiration improved a child’s muscle function and steroids, such as prednisone, slowed the rate of muscle loss, extending the time a patient could function without a wheelchair. The lifespan of boys with DMD has increased slightly, but sufferers typically die by age 30 from respiratory or cardiac failure.
“There was a dramatic change in the late 1980s,” said the late Dr. Karpati, “when the gene whose mutation causes DMD was discovered.” Researchers identified the X-chromosome gene that, when flawed, causes DMD, and named the protein that it encodes as dystrophin.
“Precise carrier detection and prenatal diagnosis were possible shortly after this discovery,” said the late Dr. Karpati. “This led to the understanding that the mutation in the gene is either inherited from the mother or occurs spontaneously in the germ cells from which the patient develops. Without the dystrophin that normally occurs at the surface of muscle fibres, muscle breakdown is relentless, regenerative capacity wears out and loss of muscle fibre occurs.”
With more informed genetic counselling, many parents who carry the defective gene are choosing not to have children and the incidence of the inherited form of DMD has dropped.
Dr. Karpati believed that there will eventually be a cure for DMD, perhaps within the next decade. “It’s very complex and it will take time, but there is reason for optimism.”
The introduction of synthetically manufactured, normal genetic coding into animal models has led to a better understanding of the function of dystrophin, but toxicity and logistical issues limit this option. Dr. Karpati was studying the potential of utrophin, a molecule similar to dystrophin that occurs on a different chromosome. And, an experimental compound shows promise for treating a genetic mutation that occurs in about 15% of DMD. “It’s unknown to what extent this will work yet, but the drug is in Phase Two trials,” said the late Dr. Karpati.
Editor’s note: Dr. Karpati passed away suddenly between the writing and publication of this article. We mourn his loss.