Researchers Find Key Nerve Injury Compound
By Maggie Fox, Health and Science Correspondent
http://dailynews.yahoo.com/h/nm/20001101/sc/health_spinal_dc_3.html
WASHINGTON, November 1, 2000 (Reuters) - Researchers said on Wednesday
they had identified a molecule that is key to helping injured nerve
cells regenerate, and said it might be used to develop new treatments
for spinal cord injuries, brain diseases and stroke damage.
The molecule, 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. It is based on a naturally occurring compound
called a nucleoside -- similar to the compounds that make up DNA.
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And in another unpublished study, Benowitz said his team found that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 brain
cells to grow new connections 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.
"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 Yahoo! Inc., and Reuters Limited.
--
Judith Richards, London, Ontario, Canada
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