People who are afflicted with muscular dystrophy (MD) are known to tire after the lightest exertion or exercise. A recent study at The University of Iowa has identified a possible cause for the exhaustion and possible drug therapy to treat the symptom. Kevin Campbell, PhD, director of the Iowa Muscular Dystrophy Center, talks about the study and the drug:
What is muscular dystrophy?
Muscular dystrophy is a large group of diseases that are genetically determined and cause progressive weakness and wasting of skeletal muscles. The primary defect is in the skeletal muscle cell.
Who is affected with muscular dystrophy?
The most common form of muscular dystrophy—Duchenne muscular dystrophy—only affects males. There are some female carriers, but in most cases, it just affects young boys.
The other forms of muscular dystrophy—both Limb-Girdle and Congenital muscular dystrophy—lthey affect both males and females. Congenital usually is early onset, and the Limb-Girdle muscular dystrophy starts anywhere between late teens and early 20s.
How is muscular dystrophy diagnosed?
Muscular dystrophy is usually diagnosed by a physical exam by a neurologist, a muscle biopsy test in some cases, and a blood test to look at muscle enzymes that are leaking into the serums.
How is the disease currently treated?
Currently there are really no effective treatments to cure muscular dystrophy. There are some treatments, like the treatment with steroids, that help, but there is no currently effective treatment to cure the disease.
What medication did your study look at to impact exhaustion in MD patients?
Our study showed that there was a misplaced enzyme in muscle cells that lead to this quick fatigue that patients exhibit with muscular dystrophy. We used genetically-engineered mice to demonstrate this and to figure out that the protein, or the enzyme called neuronal nitric oxide synthetase, is mislocalized. This enzyme is responsible for maintaining blood flow to muscles when they are contracting. So in both animal models, and, we believe, in patients, this improper blood flow to exercising muscles leads to this fatigue.
How could Viagra possibly help people with muscular dystrophy in the future?
In our study, we looked at various drugs that would possibly increase blood flow to muscle to counteract this defect, and what was very effective was sildenafil, also known as Viagra, which allows for the proper signaling to occur so that you get increased blood flow during exercise. This allowed the mice to have more activity following exercise. Viagra, which is used for other symptoms, is a very commonly used drug and has a good safety record. We think Viagra or a Viagra-like drug more specific for muscle might be useful in treating the fatigue that is exhibited by muscular dystrophy patients.
What level of increase or benefit did you see, in your early testing?
We were getting between 40 and 60 percent increase in activity following exercise. So in the mice that have the severe form of muscular dystrophy, they are almost completely inactive for 30 minutes following light exercise.
What are the next steps involved in the research?
We’re going to continue our studies on the various compounds with the drug company Pfizer to see whether there are more specific compounds or drugs that are more effective. We’re also going to see if this has any long-term benefits in terms of treating the disease. Right now we believe this drug would be useful in allowing patients to have increased physical activity and improved quality of life. However, we don’t know long term whether that would actually slow down the progression of the disease. That’s something we’re going to try to test now in the mouse models.
How long will research like this take to get to a point people with muscular dystrophy may benefit?
Since this drug is a commonly used drug, we’ve already had some discussions, both with the National Institutes of Health and Pfizer, to discuss how a clinical trial could take place. So nothing is currently planned, but hopefully in the next year something will be done to begin testing this drug and to see if it is effective. |
