From Inflammation And Autoimmunity To Nerve Regeneration And Protection

Prof. Schwartz' findings, which have the potential for being further developed into clinical therapy, have also been published in the January 1999 issue of Nature Medicine.

When tissue damage occurs, the tissue normally calls upon the immune system to repair the injured site and promote healing. However, in the case of the central nervous system of human beings and other mammals, a built-in mechanism prevents the immune system from providing effective assistance and healing.

Prof. Schwartz believes that this preventive mechanism probably developed during the course of evolution to protect the mammalian brain from the effects of the immune system: the access of immune cells to the brain would disrupt the complex and dynamic neuronal networks that build up during an individual's lifetime.

"There seems to have been an evolutionary trade-off," says Prof. Schwartz. "Higher animals protected their central nervous system from invasion by the immune system, but paid the price of forfeiting their ability to regenerate injured nerves. Thus, an evolutionary advantage that protects the healthy brain turns into a disadvantage in the case of injury."

Experiments conducted in Prof. Schwartz' laboratory; however, have revealed differences in the damage healing processes between the central nervous system and peripheral nerves. In cases involving damage to the central nervous system, inflammation-causing immune cells called macrophages are 'recruited' to the injured site at a low rate and are not optimally 'activated' and effective. By contrast, macrophages recruited to help heal peripheral nerve damage are activated and are more effective in the healing process.

Armed with this understanding, researchers have managed to overcome partially the limited ability of the central nervous system to recruit and activate macrophages to help heal damage. This was accomplished by incubating macrophages in a test tube along with damaged peripheral nerve tissue and then returning the activated macrophages to a damaged site in the central nervous system of paralyzed rats. As a result of this treatment, described in the July 1998 issue of Nature Medicine, the transplanted macrophages created a growth-inducing environment around the damaged tissue and the rats were able to regain partial motor activity in their previously paralyzed legs.

In her latest study, documented in the January 1999 Nature Medicine article, Prof. Schwartz and her team, in collaboration with a research group headed by Prof. Irun Cohen of the Weizmann Insitute's Immunology Department discovered that the same cells that cause autoimmune diseases such as multiple sclerosis-- a condition in which the immune system attacks the body's own tissues--can actually be useful in repairing damage to the central nervous system.

In the past, researcheres believed that autoimmune disease was the result of the immune system's failure to correctly distinguish between healthy 'self' and enemy 'non-self' tissue. In the course of their studies, however, Prof. Schwartz and her team have shown that autoimmunity may not always be detrimental. Autoimmunity may, in fact, have originated as an immune mechanism for dealing effectively with damage to the central nervous system.

Schwartz and her colleagues studied immune cells called T lymphocytes that attack Myelin, the protective sheath of nerves that is destroyed by the autoimmune disease multiple sclerosis. They found that, in certain circumstances, when these T lymphocytes cells were injected into rats with damaged optic nerves, these T cells reduced the optic nerve's secondary degeneration, the gradual, but often-catastrophic, loss of neurons next to the site of the initial injury.

This finding may explain why autoimmune T lymphocyte cells are so common and present even in the immune systems of healthy people: their original function may have been to maintain the integrity of the central nervous system. Only when this function for some reason goes awry, does autoimmune disease occur.

"By selectively augmenting the activity of autoimmune T cells, it may be possible to protect injured nerves without the threat of causing autoimmune disease," says Prof. Schwartz.

"Thus, both our studies--the one involving macrophages and the one on T cells--have the potential for being further developed into clinical therapy using the patient's own blood-derived cells," Prof. Schwartz adds.

Yeda Research & Development Co. Ltd., the Weizmann Institute's technology transfer arm, has approved and submitted patents for Prof.Schwartz's findings. In order to promote this research and develop it further for possible clinical use, Yeda has entered into a licensing agreement with Proneuron Biotechnology Ltd., a start-up company located in the Kiryat Weizmann Industrial Park, adjacent to the Institute.

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The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,500 scientists, students, technicians, and engineers pursue basic research in the quest for knowledge and the enhancement of the human condition. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities.