Duchenne muscular dystrophy (DMD) is caused by a genetic mutation and affects one in 5,000 boys born. Because the affected gene is on the X chromosome, girls are carriers of the mutated gene, but only very rarely (one in about 50 million) are affected.
Children with this condition will need a wheelchair by their teens, and most will die in or before their 30s.
It used to be widely believed that DMD starts in myofibers — cells involved in contraction that make up the bulk of any muscle. As a result, the search for a treatment has long focused on these cells and how to deliver therapeutics to them.
New research has shown that the disease begins much earlier in cells that are destined to become muscle fibers known as myoblasts.
The study, published in eLife, is part of an ongoing collaboration between scientists from the University of Portsmouth, CNRS, I-STEM, AFM in France and the Maj Institute of Pharmacology of the Polish Academy of Sciences
The results are significant because they change our understanding of the disease. We discovered that the functions of myoblasts are severely impaired by the lack of dystrophin, and these cells are crucial for normal muscle growth but also for regeneration.
Because these myogenic cells are not functioning, damaged muscles cannot be repaired effectively. And every myofiber that’s repaired will eventually have to be replaced, which won’t happen without myogenic cells, so it becomes a vicious cycle.”
Darek Gorecki, Senior Author, Professor, School of Pharmacy and Biological Sciences, University of Portsmouth
Last year, the team released results of modeling DMD to examine its evolution from its initial trigger and first manifestation. Even before birth, they found evidence of anomalies in the embryo. Most boys with DMD are diagnosed between the ages of two and five, by which time the damage to their bodies is already significant. This delay in recognizing the condition may prevent therapeutic interventions that could help slow, if not stop, disease progression.
‘Right now we are targeting the late stage of this disease by treating teenage patients when muscle wasting has already taken its toll,’ added Professor Gorecki.
“If instead we try to correct cells that are at the beginning of the pathological process, we may be able to delay muscle degeneration and extend a patient’s lifespan. We can do this by identifying and treating DMD neonates and targeting myogenic cells.”
According to the paper, new technologies could hold the key to developing effective therapies for this devastating disease.