From: Dan Fabulich (daniel.fabulich@yale.edu)
Date: Thu Jun 03 1999 - 17:00:06 MDT
Growing New Spinal Cells
by Kristen Philipkoski
3:00 a.m. 3.Jun.99.PDT
Spinal cord researchers have accomplished what was previously thought
impossible: tricking central nervous system cells into regeneration.
The inability of central nervous system cells to regenerate has been one of
the most religiously defended dogmas in neurobiology. But Massachusetts
General Hospital and Harvard University researchers have shown that by
damaging the sciatic nerve -- the main sensory nerve to the leg -- they can
activate growth signals in cells in the central nervous systems of
laboratory rats.
If scientists can learn how to turn on growth signals without peripheral
nerve injury, researchers may finally achieve what was once seen as an
unreachable goal: the reconnection of a severed spinal cord.
In mammals, severed nerve fibers in the central branch of the spinal cord
do not regenerate on their own. On the other hand, damaged peripheral
nerves -- those that go to the extremities -- can heal themselves. Since
the two branches, called axons, both make up the same neuron, researchers
have been trying for decades to figure out why the cells behave so
differently.
The difference in healing could be due to the cells not receiving the
signals that kick-start growth in the nerve or to inhibitors in the cells
preventing growth. Or possibly it's the result of an injury site, which
frequently develops obstacles like cysts or holes in which cells can't
grow.
"Our data looked at what happens if you can switch the cells into a growing
mode. The central branch, which never normally grows at all, began to grow
right across the central spinal cord," said study leader Clifford Woolf, of
the Neural Plasticity Research Group at the Massachusetts General Hospital
Department of Anesthesia and Critical Care and the Harvard Medical School.
The research, published in the May issue of the scientific journal Neuron,
showed cell growth into the spinal cord and above the injury site.
If the sciatic nerve and central nervous system injuries happened at the
same time, cells grew into the nervous system lesion, but not above it. But
the researchers found that if they injured the sciatic nerve one to two
weeks prior to the nervous system injury, cells grew into the spinal cord
above the lesion.
"I think it's no longer an issue of science fiction. The current technology
to identify molecules in vivo should provide new treatments, we hope within
a decade," Woolf said. "By then I think we will have made the scientific
breakthrough necessary to plan therapy."
Wise Young, professor and director of the W.M. Keck Center for
Collaborative Neuroscience at Rutgers University, believes that the
research could lead to therapy that combines the many treatments in the
works in laboratories today.
Combining cell-transfer treatments, which use fetal cells or stem cells to
fill in holes, with growth mode treatments could yield dramatic results,
said Young. Anti-inhibitor drugs, which are in clinical trials now, could
also play a part in a combined treatment.
"We've seen some functional recovery, but we've not taken all the methods
and put them together into one combination therapy. If you build a bridge
across the injury, it still won't grow all the way across because of
inhibitors." Young said.
Actor Christopher Reeve's focus on spinal cord research has helped to
advance research. Even conservative scientists are saying that they're
hopeful for successful treatments in their lifetime. But according to
experts, the funds necessary to provide therapies to people still fall
short.
The total investment in spinal cord research in the United States from both
private and government sources is less than US$100 million a year, Young
estimated. In comparison, the pharmaceutical industry estimates that it
costs an average of $300 million to take a single drug through clinical
trials and into market.
Despite the limited resources, researchers remain encouraged.
"If you had asked any neuroscientist 10 years ago whether or not we would
see a spinal cord therapy, 99 percent would have said no, not in our
lifetime, if at all," said Young. "By 1995 most scientists were saying it
could possibly happen. In 1999, the majority are saying it not only can
happen, but it will happen soon."
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