ZICHRON YAAKOV, Israel - Weizmann Institute researchers developed a treatment based on a genetically engineered fragment of the acetylcholine receptor molecule that, when administered via nasal drops, alleviates myasthenia gravis-like autoimmune disease in rats.
Details of the research were reported in the July 6, 1999, issue of the Proceedings of the National Academy of Sciences.
"We have good reason to believe that a treatment for human patients can now be developed," said research team leader Sara Fuchs, professor of immunology at the institute.
In myasthenia gravis (MG), the body's immune system mistakenly attacks the acetylcholine receptors in muscles. As the receptors are blocked by antibodies and progressively destroyed, the nerve-muscle communication is disrupted, with progressive paralysis. Fuchs's team genetically engineered that fragment of the human acetylcholine receptor that protrudes above the surface of muscle cells and reacts with various antibodies responsible for myasthenia gravis.
"Such fragments are easy to produce and far less likely to trigger the production of harmful antibodies than the entire receptor," Fuchs said.
Another major innovation is that nose drops - rather than injections - protected the rats against the myasthenia gravis-like disease, making the treatment "convenient to use" said Miriam Souroujon of The Open University of Israel, co-author on the PNAS paper with Dora Barchan and graduate student Sin-Hyeog Im.
Immunological treatments administered nasally or orally trigger a "mucosal tolerance," called that because they work through the mucosa (the soft inner lining of the nose, intestines and other organs), suppressing the undesirable autoimmune activity.
Several theories have been proposed to explain the little-understood mechanism of mucosal tolerance. The Weizmann scientists provided evidence from their experimental system that a subset of immune T cells present in the mucosa are stimulated to release substances that can actively suppress the disease-causing immune mechanism.