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News

Weizmann Institute Scientists develop a potential future treatment for Myasthenia Gravis

Weizmann Institute Of Science : 01 July, 2000  (Company News)
Weizmann Institute researchers have developed an effective treatment, administered through the nose, for a myasthenia gravis-like disease in rats, according to a report in the July 6 issue of the Proceedings of the National Academy of Sciences. The new approach used in the study may serve as a basis for treating myasthenia gravis in humans. 'More studies will be necessary before applying our approach in clinical trials, but we have good reason to believe that an effective treatment for human patients can now be developed,' said research team leader Prof. Sara Fuchs of the Institute's Immunology Department.
Weizmann Institute researchers have developed an effective treatment, administered through the nose, for a myasthenia gravis-like disease in rats, according to a report in the July 6 issue of the Proceedings of the National Academy of Sciences.

The new approach used in the study may serve as a basis for treating myasthenia gravis in humans. 'More studies will be necessary before applying our approach in clinical trials, but we have good reason to believe that an effective treatment for human patients can now be developed,' said research team leader Prof. Sara Fuchs of the Institute's Immunology Department.

The team includes graduate students Dora Barchan and Sin-Hyeog Im, and Prof. Miriam Souroujon of The Open University in Tel Aviv.

Myasthenia gravis is an autoimmune disease in which the body's immune system mistakenly attacks the receptors in muscles that pick up acetylcholine, a chemical messenger that transmits signals from nerves to muscles. As these acetylcholine receptors are blocked by antibodies and progressively destroyed, the nerve-muscle communication is disrupted and the patient develops weakness in the muscles of the face, throat and limbs. In severe cases, paralysis of respiratory muscles can be life-threatening.

Currently, many patients with myasthenia gravis are given corticosteroid drugs that suppress the immune system, but these drugs may have undesirable side effects. An ideal treatment would suppress only the immune mechanism that goes awry in myasthenia gravis, without affecting the rest of the immune system.

For more than 20 years, Prof. Fuchs has worked with the animal model for myasthenia gravis, attempting to develop a treatment that would be specific for this disease.

In the study reported in PNAS, Fuchs's team genetically engineered a fragment of the human acetylcholine receptor, the part of the receptor molecule that protrudes above the surface of muscle cells and reacts with various antibodies responsible for myasthenia gravis. Such fragments are easy to produce and are much less likely to trigger the production of harmful antibodies than the entire receptor.

Another major innovation of the study is that the receptor fragments were given through the nose rather than injected. The nose drops protected the rats against the myasthenia gravis-like disease. When the treatment was given to rats that already had the disease, their symptoms improved significantly.

In another study that has not yet been published, the scientists achieved similar therapeutic results with the same receptor fragments fed to rats.
'One of the major advantages of our approach is that genetically engineered receptor fragments appear to be safe,' Fuchs says. 'Besides, these fragments are easy to manufacture, and the treatment is convenient to use.'

Developing immunological treatments administered through the nose or orally rather than in the form of an injection is a promising area of research in autoimmune diseases. Such treatments trigger a mechanism known as mucosal tolerance, so called because it works through the mucosa, the soft inner lining of the nose, intestines and other organs. This tolerance suppresses the undesirable activity of the immune system against the body's own tissues.

Several theories have been proposed to explain the mechanism of mucosal tolerance, which is not yet fully understood. The Weizmann scientists have provided evidence that in their experimental system, the tolerance works by stimulating a subset of immune T cells present in the mucosa to release substances which can actively suppress the disease-causing immune mechanism.
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