Researchers say find key nerve injury protein

WASHINGTON (Reuters) -- Researchers said on Wednesday they had identified a protein that is key to helping injured nerve cells regenerate, and said it might be used to develop new treatments for spinal cord injuries and stroke damage.

The protein, called inosine, acts as a kind of master switch to turn on a number of genes involved in the growth of nerve cells, the team at Boston's Children's Hospital and Harvard University reports.

"Inosine switches on a whole constellation of genes," Dr. Larry Benowitz, who led the research, said in a telephone interview.

Inosine is made and licensed by Boston Life Sciences Inc. (BLSI), a tiny biotechnology firm working to develop protein-based treatments for a number of conditions.

Last year, Benowitz's team reported that inosine could cause nerve cells in rats to sprout new axons -- the tendrils that nerve cells reach out to one another with.

They plan to report at a Society of Neuroscience meeting in New Orleans later this month that when those newly grown axons met one another, they formed synapses -- the key connections that nerve cells use to send messages to one another.

And in another unpublished study, Benowitz said his team found that inosine can cause severed nerves to regenerate axons in rats. "It juices them up nicely," he said, but adding that the experiment will have to be repeated before he can be sure it really works the way he thinks it does.

Benowitz said his team found in the latest experiment, published in the Journal of Neuroscience, that inosine passes through the nerve cell's membrane and activates an enzyme that in turn controls the cell's molecular program for axon growth.

"We think it is directly targeting and activating a protein kinase, an enzyme, inside the cell, that is the linchpin of the signaling pathway that activates growth," Benowitz said.

But, he added, "While inosine stimulates nerve growth very nicely, it doesn't do it as well as another molecule we have found -- AF-1." AF-1 is short for axogenic factor and Benowitz's lab is working to get enough to experiment with.

"I have been banging my head on the wall trying to get enough of this stuff to purify," he said. "I don't think inosine alone is enough to activate everything optimally. There must be other positive and negative controls on that pathway."

Boston Life Sciences is working with other researchers to develop inosine for use in stroke victims, who lose brain cells to damage caused by blood clots. Benowitz says it is not clear whether inosine gets new brain cells to grow or protects them from dying.

When a brain cell dies, it often sends out chemical signals that cause surrounding, healthy brain cells to die. It is not known why but finding a way to shut off this mechanism could help prevent damage from stroke and brain injury, as well as the progression of Parkinson's and Alzheimer's.

Boston Life Sciences is working to try to get a product to market. The U.S. Food and Drug Administration (FDA) dealt the company a setback a year ago when it declined to approve its rheumatoid arthritis drug therafectin.

"We hope to have Inosine in the clinic sometime next year for the treatment of stroke and other CNS (central nervous system) disorders," Dr. Marc Lanser, chief scientific officer for BLSI, said in a statement.

Benowitz, who gets consulting fees and research grants from BLSI, is also funded by the National Institutes of Health, a foundation set up by paralyzed actor Christopher Reeve, and other groups.

Copyright 2000 Reuters. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

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