The National
Spinal Cord
Injury Association

Disability in the News.

New procedure holds promise for spinal-cord injury victims.

JUDY SIEGEL -- REHOVOT (July 1) - Although it won't yet help quadriplegics like actor Christopher Reeve, Weizmann Institute scientists have succeeded in partially healing the damaged spinal cords of rats, which regained partial movement in their hind legs after being paralyzed by a severed spinal cord.

"The results of our experiments are promising," said Prof. Michal Schwartz of the Rehovot institute's neurobiology department, after publication of her research in the July issue of the prestigious journal Nature Medicine.

"However, for the moment, they have been achieved only in rats, and much additional research still needs to be done before the new treatment is available to humans."

The discovery adds to the hope of para- and quadraplegics that a clinical therapy to improve neurological function in patients with spinal cord damage could be developed.

Schwartz said her team is contemplating clinical (human) trials after they conduct studies on animals whose spinal cords have suffered partial damage due to trauma (in humans, most central nervous system paralysis is due to the crushing of the spinal cord, rather than its complete severance).

"Lower" animals such have fish can repair damaged fibers in their spinal cord and brain to restore lost function. But in mammals, including humans, injuries only to peripheral nerves can repair themselves; those to the brain or spinal cord leave their victims permanently paralyzed or otherwise disabled.

Schwartz, who has been working in the field for over 15 years, hypothesized that the loss of this ability to repair nerves occurred in the course of evolution because of the need to protect the mammalian brain from the effects of the immune system.

While immune cells normally help repair damaged tissue, if they reached the brain, they would disrupt the dynamic and complex neuron networks that develop during an individual's lifetime.

When tissues are damaged, immune (white blood) cells called microphages ordinarily rush to the site of injury to remove damage cells and release chemicals that promote healing. But when a mammal's central nervous system is harmed, it is not effectively helped by the immune system.

Schwartz discovered that this is due to a mechanism in mammals that suppresses the microphages, which, in turn, swarm to injury sites in smaller numbers and fail to become optimally activated if they do arrive.

As a result of these findings, Schwartz's team managed to overcome the limited ability of the damaged central nervous system to recruit and activate the microphages.

They isolated rodent immune cells and incubated them in a test tube that contained a damaged peripheral nerve. The microphages became activated when they received the nerve's "distress signals."

The researchers then returned the activated microphages to the injury site in the paralyzed rat; the white blood cells created a growth-inducing environment around the damaged tissue.

About two months after the injury, 15 of the 22 treated rats had a partial recovery, as nerve fibers had regenerated across the injury site. The rats regained partial motor activity in their formerly paralyzed legs. Not only could they move their hind legs, but several rats were able even to place their weight on them.

Although a research team in Sweden, for example, had managed to restore some activity in paralyzed rodents by implanting segments of peripheral nerves into cut spinal cords, the Weizmann technique is regarded as very promising and innovative because it promotes the animal's self-repair mechanism and offers the option of using its own cells for this purpose.

The institute's technology-transfer arm, Yeda Research and Development Company, has applied for patents for the new treatment. It has also signed a licensing agreement with Proneuron Biotechnology Ltd., a start-up company in the Kiryat Weizmann Industrial Park next to the institute.

Injecting white blood cells into the damaged spinal cords of laboratory rats led to nerve regeneration and partial recovery of muscle function, according to a report from an international team of researchers in the July issue of Nature Medicine.

"The results of our experiments are promising," Dr. Michal Schwartz from the Weizmann Institute in Rehovot, Israel, said in a statement. "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."

Some animals, such as fish, can easily repair damaged fibers in their central nervous systems. But the spinal cords of mammals, including humans, are unable to repair themselves, so significant injury often results in paralysis.

In the study, Schwartz's team discovered that the mammalian central nervous system suppresses macrophages -- immune cells that go to an injured site to remove damaged cells and release substances that help bodies heal. Macrophages respond slowly to central nervous system injuries, and some of the cells do not become fully active at the injured site.

The researchers took macrophages from the rats and incubated them in a test tube with damaged peripheral nerves. When the macrophages received a "distress signal" from the nerves, they became activated. The researchers then placed the activated macrophages in the central nervous system of paralyzed rats, and the rats were able to partially move their previously paralyzed hind legs, with some even able to stand.

This new technique "seems to supply (damaged nerves) with cells that are an integral part of the physiological repair mechanism and can therefore facilitate self-repair," the team writes. But the process needs further research before it can be applied to humans, they conclude.  
 

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