HEALTHY EYE MUSCLES ARE CLUE TO CAUSE OF MUSCULAR DYSTROPHY

April 10, 1996
Media Contact: Marc Kusintz
Phone: (410) 955-8665
E-mail: mkusinitz@welchlink.welch.jhu.edu

"If we could treat the limb muscles so they handle excess calcium the same way eye muscles do, we might be able to reduce the damage caused by muscular dystrophy."

A team of researchers from the Johns Hopkins Wilmer Eye Institute, Children's Hospital of Harvard and laboratories in Paris and Tokyo have found that the muscles controlling eye movement protect themselves from the destructive effects of muscular dystrophy (MD) by blocking chemical reactions triggered by high calcium levels.

The researchers found that even though the extraocular eye muscles (EOM) have the same defect as other muscles--the absence of the protein dystrophin--they are not injured by high calcium levels. Dystrophin helps maintain the shape of muscle cells, and helps keep calcium stored in special compartments, called the sarcoplasmic reticulum, according to Robert Prendergast, M.D., associate professor of ophthalmology and pathology at the Johns Hopkins Wilmer Eye Institute. Prendergast is one of the authors of the paper, which was published in the Journal of Experimental Medicine. The dystrophin gene and its protein product were discovered by Louis M. Kunkel, Ph.D., professor of genetics at Harvard.

"In the absence of dystrophin, too much calcium builds up in the limb and heart muscles cells and activates enzymes inside the muscle that break down protein," says Prendergast. "But the cells of the EOM might be able to either block calcium from coming in or store it somewhere inside the cell so it can't activate those enzymes."

Previously, researchers believed that EOM might be protected from calcium entering the cells because these cells contained high levels of a substance called dystrophin-related protein, the product of a gene not related to MD. In the first part of the present study, the Harvard group found that mouse, dog and human EOM did not contain substantially greater amounts of the dystrophin-related protein than did limb muscles.

In the next series of studies led by Prendergast, drugs were used to either open muscle cell membranes to the inflow of calcium or to block the biological "pump" that pushes calcium out of the cell. This treatment caused limb muscles to whither, as they do in MD, but the EOM remained healthy.

"Since the extraocular muscles of MD patients don't have dystrophin, but still remain healthy, these muscles must be able to handle calcium in a way that limb muscles can't," Prendergast says. "This raises the possibility that if we could treat the limb muscles so they handle excess calcium the same way eye muscles do, we might be able to reduce the damage caused by muscular dystrophy."

Prendergast, in cooperation with Kunkel's laboratory, is now trying to determine how EOM are able to protect themselves from the damaging effects of high levels of calcium.

The other authors of the study include Tejvir S. Khurana (Harvard); Hala S. Alameddine, Fernando M.S. Tome and Michael Fardeau (the National Institute of Health and Medical Research, Paris); and Kiichi Arahata and Hideo Sugita (the National Institute of Health and Medical Research, Tokyo).

The research was funded by the National Institutes of Health, Research to Prevent Blindness Inc., Muscular Dystrophy Association and Association Francaise contre les Myopathies.


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