New Findings On Nerve Cell Proteins Show Promise For Reducing Disability

"Our approach is based on a natural mechanism cells have for protecting themselves, called the stress protein response," said Michael Tytell, Ph.D., a neuroscientist and the study's lead researcher. "We believe it has potential for preventing some of the disability that occurs as a result of nervous system trauma and disease."

The research showed that up to 50 percent of the motor and sensory nerve cell death could be prevented in mice with sciatic nerve injury. It is reported in the current issue of Cell Stress and Chaperones, a journal of stress biology and medicine.

"We are on our way to developing a treatment that is effective in preventing motor nerve cell death, which is significant to people because loss of motor neurons means paralysis," said Tytell, professor of neurobiology and anatomy at Wake Forest Baptist.

The goal of the work is to prevent or minimize the "secondary" cell death that occurs in the hours and days after a spinal cord or brain injury. During this period, cells surrounding the injury can become inflamed and die, a cascading response that worsens disability.

"There is a lot of cell death that takes place after the initial injury," said Tytell. "If you could prevent that, you would retain a lot more function."

Tytell's approach is to augment the stress protein response, in which cells produce proteins called Hsc70 and Hsp70 that help protect them from death when they are exposed to heat, injury or any other stresses that threaten their normal function.

"This is a way cells have of protecting themselves," he said. "If we can figure out a way to facilitate that response, we could potentially limit the amount of damage that is caused."

For the study, the researchers treated injured sciatic nerves in mice with Hsc70 and Hsp70. In mice treated with the proteins, cell death was reduced by up to 50 percent compared to mice that weren't treated.

Tytell said it is a novel idea that cells can be successfully treated with a protein that is ordinarily made inside the cells.

"We don't know whether the protein is functioning in the same way as when it's made in the cells," he said. "We're working to learn more about this effect. If we can understand it better, we'll know what form it should be in and what the doses should be to maximize the protective benefits."

Tytell and colleagues hope to use their knowledge about the proteins and how they work to develop drugs that could be used to treat injury. One idea is to develop a drug that would increase the production of the protective proteins.

Tytell said that over the years, there has been little progress in research on traumatic injury to the nervous system. One approach that is being studied is to replace the damaged cells with stem cells. However, there are technical problems getting the nerve "circuitry" to grow back to normal. He believes the idea of protecting cells from secondary cell death deserves additional research attention.

"That's a goal we could potentially reach more quickly than replacing cells that are lost," he said.

A long-range goal is to determine if the proteins could be useful in the treatment of degenerative diseases of the brain, such as Alzheimer's disease and Huntington's disease. The research was supported by a grant from the Muscular Dystrophy Association, a Wake Forest University School of Medicine Venture Grant, and a private donation.

Tytell and Wake Forest hold a U.S. Patent on the use of Hsc70 and Hsp70 to prevent the death of injured cells. The results in the report will contribute to his efforts and those of his co-author, Lucien J. Houenou, a former faculty member of Wake Forest University School of Medicine, to develop therapeutic agents based on the cellular stress response.