Scientists Block Loss Of Eyesight In Animals With A Glaucoma-Like Disease


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Weizmann Institute scientists have succeeded in stopping the progressive loss of eyesight in animals with a glaucoma-like disease. Their innovative study, reported in the March 6, 2001 issue of the Proceedings of the National Academy of Sciences U.S.A., suggests that Copaxone, a drug developed at the Weizmann Institute of Science to treat multiple sclerosis, may also stop, or at least slow down, the loss of eyesight in people with chronic glaucoma.

Glaucoma, which affects 1 percent of the adult population, is the main cause of blindness in adults. The majority of patients with chronic glaucoma have increased pressure inside the eye due to defective drainage of the transparent fluid that bathes the eye and nourishes its outer cells. The increase in this intraocular pressure (IOP) damages the optic nerve, causing it to degenerate and often leading to loss of eyesight.

For many years, the search for improved glaucoma therapies focused on correcting the eye's drainage system to reduce IOP. Eventually, however, it became clear that reducing the pressure was not enough to halt the ongoing degeneration of the optic nerve and did not eliminate the risk of blindness. Scientists concluded that a crucial factor was being overlooked and they set out in search of this missing link.

Approximately five years ago, Prof. Michal Schwartz of the Weizmann Institute's Neurobiology Department proposed a new concept to account for the continuing degeneration of the optic nerve that occurs after the pressure in the eye had been reduced. Schwartz suggested that while the initial damage to the optic nerve is indeed caused by increased eye pressure, secondary factors triggered by the initial damage contribute to the nerve's ongoing degeneration. The offending factors include chemicals that play an important role in the life of a healthy nerve, but when the nerve degenerates, their concentrations increase to a toxic level. One of these chemicals is the neurotransmitter glutamate, which spills from damaged nerve cells and adversely affects healthy neighboring cells.

In line with this concept, Prof. Schwartz developed an original strategy for tackling the problem. To protect the nerve from harmful substances coming from the body itself, she recruited the immune system, whose well-known role is to defend the body against outside 'invaders.' This approach at first raised a few eyebrows, mainly because it involved cells that, when activated, usually cause one of the autoimmune diseases in which the body mistakenly attacks itself, such as juvenile diabetes or multiple sclerosis. The concept of using these 'enemy' cells to heal the body seemed uncanny.

Prof. Schwartz, who has also developed an immune-based therapy for spinal cord injuries now being tested in a clinical trial, believes that contrary to accepted wisdom autoimmunity can play a beneficial role in the body. A series of studies in her lab has shown that immunization with fragments of proteins belonging to myelin, the protective sheath of the nerves, can prevent degeneration of the damaged optic nerve. However, the use of such protein fragments, or peptides, for immunizing people is fraught with risk because some of these peptides cause the immune system to attack nerve fibers, leading to multiple sclerosis. Since humans vary greatly in their genetic makeup, it is difficult to establish which of the peptides would cause disease in a specific patient.

Looking for a safe alternative to these peptides, Schwartz and her group, in collaboration with Profs. Irun Cohen and Michael Sela of the Weizmann Institute's Immunology Department, demonstrated that immunization with Copaxone, a synthetic compound that reacts with cells that respond to self-proteins, protects the damaged optic nerve from neuronal degeneration. Copaxone was developed at the Institute by Dr. Dvora Teitelbaum, Prof. Ruth Arnon and Prof. Michael Sela as a drug for multiple sclerosis.

In the present study, the scientists sought to establish how Copaxone produces its protective effect on the nerve. This research -- conducted by Prof. Schwartz, Dr. Eti Yoles and graduate students Jonathan Kipnis and Hadas Schori -- showed that immunization with Copaxone shields the nerve from the toxic effects of the neurotransmitter glutamate. These findings strongly suggest that Copaxone immunization is a potential therapy for glaucoma, in which the optic nerve undergoes degeneration and glutamate levels rise. Indeed, in another series of experiments conducted together with scientists from the U.S. company Allergan, Inc. (who developed the rat model that simulates chronic glaucoma), Copaxone immunization proved even more effective. In rats immunized with a single injection of Copaxone, only about 4 percent of nerve cells died in the glaucoma-affected eye, compared with 28 percent in rats that were not immunized. Thus, immunization with Copaxone dramatically protected the nerve from pressure-induced death.

Following the success of this research, trials in human patients with glaucoma are expected to begin soon. Scientists hope that the trials will be facilitated by the fact that the U.S. Food and Drug Administration has already approved Copaxone.

Prof. Michal Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology. Her research is supported by the Alan T. Brown Foundation to Cure Paralysis, the Glaucoma Research Foundation and the Jerome and Binette Lipper Award.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel. Its 2,500 scientists, students and support staff are engaged in more than 1,000 research projects across the spectrum of contemporary science.