The gene discovery leads the way
Since the disorder affects mainly boys, scientists already knew that the gene responsible for DMD must be on the X chromosome. By studying the X chromosomes of children with DMD, researchers in 1986 pinpointed the defective gene responsible for the disorder. Then it was discovered that this gene was responsible for the production of a muscle protein that researchers hadn't known about. It was named "dystrophin," and as it was studied, researchers learned that it had a key role in muscle function. An almost complete absence of dystrophin was at the root of DMD.
Dystrophinopathies
Researchers also realized that there was a group of disorders based on the newly-discovered dystrophin. It had long been known that Becker MD was similar to Duchenne MD, but with milder symptoms. Becker MD, as it turned out, results from a less severe dystrophin deficit than DMD. There is also a heart problem (X-linked cardiomyopathy) that results from the loss of dystrophin in heart muscle.
Fixing the defective gene
Since researchers know exactly which gene is the problem, it seems logical that they should be able to go in and fix it with a replacement gene. Once the muscles received the new gene, they would start making dystrophin, which would stop the disorder.
Unfortunately, this turns out to be a complicated proposition. Gene therapy for DMD would involve using a disabled virus (the vector) to carry the substitute gene to the muscles. Researchers have encountered three major obstacles in their work:
- If the body recognizes the vector as a virus, it may attack and destroy it. Researchers have to develop a vector that can sneak past the body's defenses.
- People with DMD have little or no dystrophin in their bodies. If the body begins making dystrophin, the immune system may attack it as a "foreign" protein, thinking that it doesn't belong in the body.
- The dystrophin gene is one of the largest genes found to date. The whole thing doesn't fit inside a virus vector. Researchers had to make a "mini-gene" with the most important parts and have been trying to see if it will work.
Taking an alternate route
While research proceeds on dystrophin gene therapy, other ways to treat DMD are being explored. There is another protein similar to dystrophin, called utrophin, which may be able to substitute for it. A study with mice that had muscular dystrophy showed that this was possible. Researchers now are trying to develop medications that get the body to produce lots of utrophin. Since utrophin is already in the body, the immune system leaves it alone.
The future
There are several goals that gene research has for Duchenne MD and Becker MD. The first is to stop the progression of the disorder in someone who already has it. The second is to not only stop the disorder, but repair the damage it has done. The third and best goal is to prevent the disorder from occurring at all. This is the hope for the future of MD research.
Information for this article was taken from:
- Muscular Dystrophy Association USA. "Steps taken toward utrophin therapy for Duchenne." Research Updates, Vol. 6, No. 3, June 1999.
- Muscular Dystrophy Association USA. "Progress in utrophin therapy for DMD." Research Updates, Vol. 7, No. 1, Feb 2000.
- National Center for Biotechnology Information. Genes and Disease: Duchenne Muscular Dystrophy.
- Burke, Wylie. "Genomics as a Guide to Disease Classification." Notes from presentation given at the American Association for the Advance of Science Exposition, Boston, MA, 2/15/02.
