SLU researchers show how to stop muscle weakness caused by myasthenia gravis

December 20, 2007

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.
-end-
In addition to Kaminski, the study's authors include Yuefang Zhou, Ph.D., and Bendi Gong, Ph.D., both of Saint Louis University; M. Edward Medof, M.D., and Feng Lin, Ph.D., both of the Institute of Pathology at Case Western Reserve University in Cleveland; and Russell Rother, Ph.D., of Alexion Pharmaceuticals in Cheshire, Conn.

The research was supported by grants from the National Institutes of Health.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

Saint Louis University

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.