Under a new $4.7 million grant from the National Eye Institute, researchers from the Case Western Reserve University School of Medicine and University Hospitals of Cleveland (UHC) hope to develop in five years a drug ready for human clinical trials to treat myasthenia gravis, an autoimmune disease that weakens muscles, affects vision—and in the most severe cases—puts patients on artificial ventilation.

According to the National Eye Institute, this is the largest single project grant it has awarded to an Ohio institution.

The new grant to Henry J. Kaminski, a professor in the department of neurology and a member of the Visual Sciences Research Center at Case and UHC, brings together a group of experts well-versed in the disease, muscle biology, genetics and drug development who are associated with Case, UHC and the Louis Stokes Cleveland Department of Veterans Affairs Medical Center.

Among the unique features of this research project is that it will be the first to apply genomic analysis to this disorder and will be the first to comprehensively investigate eye muscle involvement by the disease.

In autoimmune diseases, the immune system malfunctions and mistakes a part of the body as foreign and mounts an attack on it. According to Kaminski, in myasthenia gravis the immune system produces antibodies that attack the receptors on the muscle side of the neuromuscular junction. The antibodies cause damage by activating another part of the immune system called the complement system, which is a group of proteins designed to protect against infectious invaders.

"We hope to design a drug that inhibits complement activation specifically at the nerve-muscle communication point," said Kaminski. "Although there currently are several treatments that are beneficial in treating the disease, they have numerous adverse effects. We hope our treatment would be a more effective one with less side effects."

Although the disease is relatively rare with a prevalence of about 400 cases in one million people, it is the best-understood autoimmune disease, according to Kaminski.

"Understanding this disease will likely provide new insights of other disorders," he said.

The grant brings together a diverse group of scientists with individual interests in: complement (Edward Medof and Feng Lin, both in the pathology department), genomic analysis (John Porter, in the neurology department), eye movement control (John Stahl, in the neurology department), the question of understanding myasthenia gravis (Kaminski) and drug development (Charles Hoppel in the pharmacology department).

Medof already has developed complement inhibitors, and during the first three years of the grant, the researchers will test several ways to adapt these inhibitors to precisely target the nerve-muscle communication points. In the last two years of the study, they will test their lead drug for safety.

As part of their work, Porter will use sophisticated DNA analysis to evaluate precisely how muscles are affected on the genetic level by myasthenia gravis. He will use DNA microarray analysis, which can identify nearly all genes functioning (or expressed) in a tissue.

People with myasthenia gravis may call UHC's Myasthenia Gravis Center, directed by Kaminski, at 216-844-3744.

Return to the online edition of the 12-11-03 Campus News.