Can we enlist substitute genes to fight muscular dystrophy

(Philadelphia, PA) Substitutes. If your teacher is out sick or the secretary is on vacation, calling in a substitute is always an option. But what if one of your genes is not working? In recent years, researchers have eyed utrophin as a substitute for a similar gene, dystrophin, which is responsible for Duchennes muscular dystrophy (DMD), a fatal neuromuscular disease. In the May 15th issue of the Journal of Neurological Sciences, researchers at the University of Pennsylvania School of Medicine detail the cellular mechanisms that promote and regulate the transcription of the utrophin gene into protein. Their findings may open the door to creating therapeutics that will produce excess utrophin in people suffering from DMD.

Utrophin has been a major focus in muscular dystrophy. Dystrophin and utrophin perform similar tasks at the neuromuscular junction where nerve cells meet muscle tissue and studies have shown that utrophin over-production reverses the symptoms of muscular dystrophy in mice, said Tejvir S. Khurana, MD, PhD, assistant professor in the Department of Physiology and researcher at the Pennsylvania Muscle Institute at Penn. It is not a perfect substitute in the way that a putter is not the same as a driver if you are playing golf, for example. But when you are on the fairway and your driver is broken, you can use your putter you just have to hit the ball much, much harder. Duchennes muscular dystrophy is one of the most frequent hereditary diseases of men, affecting one in 3,500 boys. DMD occurs when the dystrophin gene, located on the short arm of the X-chromosome, is broken. Since males only carry one copy of the X-chromosome, they only have one copy of the dystrophin gene. Without the dystrophin protein, muscle tissue cannot compensate sufficiently and will eventually break down. Over-production of utrophin may be a viable alternative to adding a working copy of the dystrophin gene through gene therapy, said Khurana. The available rese

Contact: Greg Lester
University of Pennsylvania School of Medicine

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