Rebif Spells Relief

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Prof. Michel Revel

 

A new drug for multiple sclerosis, the second MS medication to emerge recently from Weizmann Institute research, promises relief for the many victims of this debilitating condition.

For a million young people around the world, the joys of young adulthood are hearsay. What should have been the best years of their lives have been transformed into a series of unpredictable nightmares as they cope with episodes of relapsing-remitting multiple sclerosis. When an attack comes on, these 20- and 30-something victims can experience numbness, tingling, weakness or even paralysis of the limbs, general fatigue, blurred vision and even blindness.

Multiple sclerosis is an autoimmune disease. Mistaking the body's own cells for foreign invaders, the immune system attacks and destroys the myelin sheath that insulates nerves. Messages moving along the nerve fibers are interrupted before they can reach their destination, resulting in loss of function.

Help is now on the way in the form of a new recombinant drug based on the research of Weizmann Institute virologist Prof. Michel Revel of the Molecular Genetics Department. Interferons, the subject of Revel's research for more than 30 years, play a key role in the immune system. The beta-interferon cloned and developed in his laboratory delays relapses of multiple sclerosis.

The new drug is a genetically engineered form of beta-interferon, derived from a mammalian cell line. Called Rebif®, for recombinant beta-interferon, the new medication results from a long-standing collaborative effort between the Weizmann Institute and InterPharm Laboratories Ltd., a subsidiary of the Swiss pharmaceutical company Ares-Serono. InterPharm's beta-interferon plant, in the Kiryat Weizmann Science Park, is one of only a few genetic engineering facilities in the world that use mammalian cell technology to produce molecules identical to human proteins. It is this characteristic that makes Rebif® easy for patients to tolerate.

Ares-Serono reports that clinical trials in Europe over the past two years have demonstrated Rebif®'s effectiveness. In Hamburg, Germany, neurologist and multiple sclerosis specialist Dr. Wolfgang Elias has been prescribing the new drug and monitoring his patients' reactions.

"My patients have 50 percent fewer relapses, meaning fewer days when they are incapable of work, and less neurological regression," says Elias.

According to Ares-Serono, more than 2,000 patients in 15 countries are now participating in clinical trials being carried out by the company. This is the most comprehensive worldwide research program ever carried out for the treatment of multiple sclerosis, covering the relapsing-remitting form of the disease as well as secondary progressive and early-onset MS.

Rebif® is the second multiple sclerosis medication to be developed through research conducted at the Weizmann Institute. In December 1996, the U.S. Food and Drug Administration approved the use of Copaxone® for this disease. The drug, produced by Israel's Teva Pharmaceutical Industries Ltd., was originally synthesized and developed by Profs. Ruth Arnon and Michael Sela and Dr. Dvora Teitelbaum of the Institute.

Prof. Revel holds the Ruth and Jerome A. Siegel and Freda and Edward M. Siegel Chair of Virology; Prof. Arnon, the Paul Ehrlich Chair of Immunology and Prof. Sela, the W. Garfield Weston Chair of Immunology. Research facilities: Estate of Morris Goldstein, Fort Lauderdale, Florida.
Life Sciences
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Nothing To Sneeze At

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A gene responsible for producing a protein that blocks allergic reactions has been discovered and studied by a team led by Prof. Israel Pecht of the Institute's Immunology Department.

In an allergic reaction, an allergen such as pollen triggers the immune system to respond abnormally, setting off a series of molecular processes that cause mast cells on the surface of the lungs, nose and other tissues to release chemicals. The result: the familiar bouts of wheezing, sneezing, or other reactions.

Pecht's team discovered that when molecules of a certain protein found on the membranes of these mat cells group together, they can interfere with the biochemical processes that lead to an allergic reaction. The scientists studied the structure of this protein, known as mast-cell-function-associated antigen (MAFA), and the gene responsible for its production, and found that it probably plays a role in intercellular communications.

In the future, it may be possible to prevent allergic reactions by designing medications that mimic the action of MAFA.
Life Sciences
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Improved Bone Marrow Transplants in Leukemia Patients

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Researchers from the Weizmann Institute and Perugia University in Italy have developed a method that may significantly improve the chances for people with leukemia to receive potentially life-saving bone marrow transplants. Whereas today many leukemia patients fail to find properly matched marrow donors, the new approach -- whose effectiveness still needs to be confirmed in further studies -- may allow them to receive transplants from unmatched individuals, thus making marrow transplantation available to all those in need of the treatment.

The method was developed over the past eight years by Prof. Yair Reisner of the Institute's Department of Membrane Research and Biophysics and Prof. Massimo F. Martelli of the University of Perugia's Policlinico Monteluce in Perugia, Italy.

When the first 17 patients were treated in Italy with their technique, the donor marrow -- drawn from family members who were not entirely compatible with the recipients -- successfully implanted itself in 16 of the cases. Although all the patients had been in terminal stages of leukemia, six were free of the disease when study results were summed up.

Bone marrow transplantation (BMT), a last-resort treatment for leukemia and other disorders, consists of wiping out the patients' immune system and the diseased bone marrow, and infusing them with healthy marrow. Transplanting marrow from unmatched donors has been problematic because, despite the pre-treatment, the patients' residual immune cells may recognize the incompatible transplant as "foreign" and reject it.

The new approach eliminates the requirement for a very close match between donor and recipient by using up to ten times the normal amounts of transplanted marrow. Such "megadoses" appear to be effective because they give transplanted cells an edge in their competition with residual recipient cells, thereby minimizing the risk of rejection.

In addition, the collected marrow is purified using a technique developed by Reisner some ten years ago to enable "bubble" children with severe combined immunodeficiency diseases to undergo BMT. This multi-stage process -- which was also used in treating several victims of the nuclear accident at Chernobyl -- prevents a severe complication known as graft-versus-host disease.

Although the "megadose" method has thus far been tried only in people with leukemia, in the future it may be modified to treat noncancerous blood disorders, such as sickle-cell anemia, and to facilitate organ transplantation.
Life Sciences
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