Working with the Enemy


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Prof. Michal Schwartz: MS drug may treat glaucoma

Glaucoma is the leading cause of blindness in adults, affecting one percent of the adult population. Weizmann Institute scientists have now succeeded in putting the brakes on progressive eyesight loss in experimental animals afflicted with a glaucoma-like disease. Their study, reported in Proceedings of the National Academy of Sciences, U.S.A., suggests that Copaxone, a drug developed at the Weizmann Institute to treat multiple sclerosis, may also stop, or at least slow down, eyesight loss in people with chronic glaucoma.

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. This intraocular pressure (IOP) damages the optic nerve, causing it to degenerate and often leading to blindness. (Operating much like an electric cable, the optic nerve is a bundle of more than 1 million nerve fibers, which carry the images we see to the brain.)

For many years, the search for improved glaucoma therapies focused on correcting the eye's drainage system to reduce IOP. Eventually however, it became apparent that reducing the pressure was not enough to arrest glaucoma, as it did not halt optic nerve degeneration. Scientists concluded that a crucial factor was somehow 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 continued optic nerve degeneration occurring in spite of successful treatments to reduce eye pressure. 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. When the nerve is damaged, chemicals that normally play an important role in neuronal cell maintenance 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, Schwartz developed an original strategy for tackling the problem. To protect the nerve from the harmful chemicals in the body, she recruited the immune system (although its well-known role is actually to defend the body from external "invaders"). This approach raised eyebrows at first, 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 and multiple sclerosis. The concept of using these "enemy" cells to heal the body seemed uncanny.

Schwartz - who has also developed an immune-based therapy for spinal cord injuries now undergoing clinical trials - has demonstrated that contrary to accepted wisdom, autoimmunity can play a beneficial role in the body. A series of studies in her lab showed that in rats, immunization with protein fragments from myelin, the sheath enveloping nerves, reduces the extent of degeneration after acute injury of the rat optic nerve or spinal cord. However, the clinical use of such protein fragments, or peptides, for immunization 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 make-up, it is difficult to establish which of the peptides would be risky in a specific patient.

Looking for a safe alternative to these peptides to treat glaucoma, Schwartz and her group, in collaboration with Profs. Irun Cohen and Michael Sela of the Weizmann Institute's Immunology Department, turned to Copaxone, a synthetic compound which reacts with immune cells that recognize and respond to self proteins. Copaxone was developed at the Institute by Dr. Dvora Teitelbaum and Profs. Ruth Arnon and Michael Sela as a drug for multiple sclerosis. The team demonstrated that in glaucoma, immunization with Copaxone protects the damaged optic nerve from neuronal degeneration. And the most recent study by Schwartz, Dr. Eti Yoles, and graduate students Jonathan Kipnis and Hadas Schori may explain why. The Weizmann team found that immunization with Copaxone shields the nerve from the toxic effects of neurotransmitter glutamate. These studies were corroborated in another series of experiments, conducted together with scientists at the U.S. based company Allergan Inc. (who developed the rat model that simulates chronic glaucoma). In rats immunized with a single injection of Copaxone, only about 4 percent of the nerve cells in the glaucoma-affected eye died, compared with 28 percent in the control group. These collective findings strongly suggest that Copaxone immunization is a potential therapy for glaucoma. Following these findings, trials in human patients with glaucoma are expected to begin shortly. Scientists hope that the trials will be facilitated by the fact that the U.S. Food and Drug Administration has already approved the use of Copaxone.