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SLU researchers show how to stop muscle weakness caused by myasthenia gravis
December 21, 2007Findings could lead to treatments for related autoimmune disorders such as arthritis, lupus
Severe muscle weakness caused by myasthenia gravis - a highly debilitating autoimmune disorder - can be prevented or reversed by blocking a key step in the immune response that brings on the disease, researchers at the Saint Louis University School of Medicine have found.
Myasthenia gravis, which affects about 120,000 Americans, is caused when the immune system produces antibodies that attack and damage acetylcholine receptors, which are mechanisms that play a key role in transmitting the electrical impulses that cause muscles to move and contract.
The immune response at the heart of this process is called a complement cascade - a complex chain of chemical reactions in which proteins bind together to attack a cell by punching a hole in it. When acetylcholine receptors are damaged in this way, muscle movement is severely impaired.
Using an animal model, the SLU scientists found they could prevent muscle weakness, or restore muscle strength, caused by myasthenia gravis by stopping the complement cascade at a step called C5 - before the series of chemical reactions had finished. They did this by administering an anti-C5 agent, which targets one of the proteins involved in the cascade and thus stops the process.
The researchers' findings are published in a recent edition of the Journal of Immunology (http://www.jimmunol.org/cgi/reprint/179/12/8562).
Henry J. Kaminski, M.D., professor and chairman of the department of neurology and psychiatry at the Saint Louis University School of Medicine, one of the study's authors, said the findings are promising enough that human clinical trials involving the anti-C5 agent - called eculizumab - are likely within a year.
"We believe this therapeutic approach has strong potential for improving the lives of patients with myasthenia gravis," Kaminski said. "And if it proves successful there, it could also one day help us find new therapies for other auto-immune disorders, such as rheumatoid arthritis and lupus."
Myasthenia gravis affects approximately 400 per 1 million people. The severe muscle weakness caused by the disease brings a host of other complications, including difficulty breathing, difficulty chewing and swallowing, slurred speech, droopy eyelids and blurred or double vision. By preventing or reversing the muscle weakness, the other symptoms are prevented or reversed as well.
Myasthenia gravis can't be cured, but it is sometimes be treated with surgery to remove the thymus (which plays a role in the immune system) or with various drugs. Surgery often doesn't bring relief, however, and the medications typically decrease in effectiveness over time or, in the case of immunosupressants and corticosteriods, have severe side effects.
Saint Louis University
The immune response at the heart of this process is called a complement cascade - a complex chain of chemical reactions in which proteins bind together to attack a cell by punching a hole in it. When acetylcholine receptors are damaged in this way, muscle movement is severely impaired.
Using an animal model, the SLU scientists found they could prevent muscle weakness, or restore muscle strength, caused by myasthenia gravis by stopping the complement cascade at a step called C5 - before the series of chemical reactions had finished. They did this by administering an anti-C5 agent, which targets one of the proteins involved in the cascade and thus stops the process.
The researchers' findings are published in a recent edition of the Journal of Immunology (http://www.jimmunol.org/cgi/reprint/179/12/8562).
Henry J. Kaminski, M.D., professor and chairman of the department of neurology and psychiatry at the Saint Louis University School of Medicine, one of the study's authors, said the findings are promising enough that human clinical trials involving the anti-C5 agent - called eculizumab - are likely within a year.
"We believe this therapeutic approach has strong potential for improving the lives of patients with myasthenia gravis," Kaminski said. "And if it proves successful there, it could also one day help us find new therapies for other auto-immune disorders, such as rheumatoid arthritis and lupus."
Myasthenia gravis affects approximately 400 per 1 million people. The severe muscle weakness caused by the disease brings a host of other complications, including difficulty breathing, difficulty chewing and swallowing, slurred speech, droopy eyelids and blurred or double vision. By preventing or reversing the muscle weakness, the other symptoms are prevented or reversed as well.
Myasthenia gravis can't be cured, but it is sometimes be treated with surgery to remove the thymus (which plays a role in the immune system) or with various drugs. Surgery often doesn't bring relief, however, and the medications typically decrease in effectiveness over time or, in the case of immunosupressants and corticosteriods, have severe side effects.
Saint Louis University
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