Innovative Treatment Enables Paralyzed Rats to Regain Partial Use of Their Hind Legs

REHOVOT, Israel -- June 30, 1998 -- Weizmann Institute scientists have managed to partially heal the damaged spinal cords of laboratory animals, according to a study reported in the July issue of Nature Medicine. A team led by Prof. Michal Schwartz of the Neurobiology Department used an innovative treatment which allowed rats to regain partial movement in their hind legs that had been paralyzed by damage to the spine.

"The results of our experiments are promising," says Prof. Schwartz. "However, for the moment they have only been achieved in rats, and much additional research still needs to be done before the new treatment is available to humans."

It has long been known that "lower" animals, such as fish, can repair damaged fibers in the central nervous system -- the spinal cord and the brain -- and restore lost function. In contrast, mammals, including humans, can only repair injuries to the peripheral nerves, while injuries to the brain or spine leave them permanently paralyzed or otherwise handicapped.

The new approach is based on Schwartz's theory which states that the loss of this repair ability occurred in the course of evolution due to a unique relationship between the central nervous and the immune systems. More specifically, Schwartz believes this loss was probably dictated by the need to protect the mammalian brain from the effects of the immune system: While immune cells normally help to heal damaged tissue, their access to the brain would disrupt the complex and dynamic neuronal networks that build up during an individual's lifetime.

Generally, when tissue damage occurs, immune cells known as macrophages swarm to the injured site where they remove damaged cells and release substances that promote healing. The central nervous system of mammals is different in this regard: when damaged, it is not effectively assisted by the immune system.

Schwartz's team discovered that this is because the mammalian central nervous system has a mechanism that suppresses the macrophages. As a result, macrophages are recruited to central nervous system injuries at a lower rate, and those that are recruited fail to become optimally "activated" and effective.

These findings led to a series of experiments with rats in the course of which the researchers managed to overcome the limited ability of the damaged central nervous system to recruit and activate the macrophages. They isolated macrophages and incubated them in a test tube in the presence of a damaged peripheral nerve. The macrophages, which received the distress signals of the damaged peripheral nerve, became activated.

At this stage, the researchers returned the activated macrophages to the damaged site in the central nervous system of the paralyzed rat. The transplanted macrophages created a growth-inducing environment around the damaged tissue. As a result of the treatment, the rats were able to regain partial motor activity in their previously paralyzed legs. They were able to move their hind legs and several animals were even able to place their weight upon them.

A major innovative aspect of such treatment lies in promoting the animal's own self-repair mechanism. In fact, the new treatment offers the option of using the animal's own cells for this purpose.

Further research is necessary to see if this approach will work in "higher" animals, such as humans.

Yeda Research & Development Co. Ltd., the Weizmann Institute's technology transfer arm, has submitted patent applications for the new treatment. 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.