Hyde Turned Jekyll

While crucial to warding off disease, immune cells have traditionally been thought to be potentially damaging to the central nervous system (CNS) - the brain and the spinal cord. However, a team of Weizmann Institute scientists has now found that immune cells can be recruited to treat partial spinal cord injuries.

Severing the spinal cord causes complete paralysis of the organs innervated by the central nervous system, from the point of injury downward. In fact, even a partial injury of the spinal cord may cause complete paralysis, due to the "hostile environment" created by damaged fibers causing harm to the undamaged fibers. As a result, even in cases of partial spinal cord injury, the damage continues to spread, intensifying the paralysis. Blocking the spread of damage may therefore save the nerve cells undamaged by the initial trauma - and with them, at least some of the patient's motor activity.

Several years ago, a team of Weizmann researchers led by Prof. Michal Schwartz of the Neurobiology Department found that following neuronal injury, immune cells known as macrophages may be recruited to encourage repair and renewed growth of damaged nerve fibers. Schwartz now hopes to take this research one step further. In a study recently published in The Lancet, she proposes adding additional immune cells, known as T-cells, to the damage-control battalion aimed at blocking the spread of damage.

At first glance, this idea seems to oppose the widespread view of immune cells as potentially damaging to the central nervous system. Indeed, while macrophages normally help to heal damaged tissue, previous research by Schwartz revealed that the mammalian CNS actually suppresses an immune response following injury. This suppression may be the result of an evolutionary trade-off. In contrast to fish and other lower life forms capable of repairing damaged CNS fibers, humans and other mammals can repair only peripheral nerves, while injuries to the brain or spine leave them permanently paralyzed or otherwise handicapped.

To get smart, higher animals may have had to pay a price, Schwartz suggests. Along with the asset of complex brains capable of continuous learning came a disadvantage - loss of the self-healing ability existing in lower vertebrates. "The need to prevent immune cells from "remodeling" the brain may have dictated losing the tissue-repair capacity since the immune cells could disrupt the complex and dynamic neuronal networks that build up during a lifetime," says Schwartz.

T-cells prevent infection by seeking out and destroying pathogenic "enemies" that infiltrate the body. But the body also contains T-cells that are directed against its own components. The accepted notion is that these anti-self T-cells may cause autoimmune diseases, such as multiple sclerosis and diabetes. However, the Institute scientists have shown that a controlled amount of these autoimmune cells, when directed against specific components, can assist in curbing injury-induced neuronal damage.

Following treatment with anti-self T-cells, rats with partial injuries of the spinal cord regained some motor activity in their previously paralyzed legs while untreated rats developed increasing and sometimes even total paralysis. These findings may lead to an innovative clinical treatment for preventing total paralysis after partial spinal cord injury.

Immune cells have a double-edged sword potential in treating neuronal injuries, Schwartz explains. The key to using them effectively is to extract the cells from the patients blood and increase their amount and activity in such a way that their healing effect is maximized while their potential risk is minimized. The cells are then reintroduced into the damaged neuronal area. Schwartz: "The concept is to work together with the body's existing self-repair mechanism, which apparently requires encouragement and monitoring."

Other scientists participating in this study were Weizmann Profs. Irun Cohen of the Immunology Department, Michal Neeman of the Biological Regulation Department, and Prof. Solang Akselrod of Tel Aviv University. Working with Prof. Michal Schwartz were Dr. Eti Yoles, Dr. Eugenia Agranov, Ehud Hauben, Uri Nevo, and Gila Moalem, all of the Neurobiology Department.

Prof. Michal Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology. Her research is funded Proneuron Ltd., the Alan T. Brown Foundation to Cure Paralysis, New York, the Glaucoma Research Foundation, San Francisco, California, and the Jerome and Binette Lipper Award.