Tuesday Nov 13th, 2001
Two types of cell transplants hold
off muscle atrophy in mouse models of amyotrophic lateral sclerosis (ALS).
These results offer hope that cell transplants could one day be used to
treat this devastating and incurable disease, two research groups announced
here this week.
ALS, also known as Lou Gehrig's disease,
causes spinal-cord neurons that communicate with muscles to waste away,
leading within five years to muscle weakness, then paralysis and death.
Despite the efforts of researchers, there's little physicians can do for
ALS patients; the only FDA-approved drug, sriluzole, prolongs life just
six months.
As an alternative to drugs, Svitlana
Garbuzova-Davis and Paul Sanberg of the University of South Florida in
Tampa and their colleagues tried transplanting cells called hNT neurons
into the spinal cords of mice that had a disease model of ALS. These hNT
neurons, which are stable neuron-like cells derived from a human cancer
line, are the only cell line approved by the FDA for neural transplants
into humans. So far, they've shown promising results in the clinical trials
for stroke patients, and they also seem to help animals with Parkinson's
disease, Huntington's disease, and spinal cord injury.
In earlier work, which is in press
at the Brain Research Bulletin, the researchers showed the hNT tranplants
survived in the spinal cord of mutant mice that would soon have developed
symptoms of ALS. The treatment prevented degeneration of spinal cord neurons,
which helped ALS-afflicted mice live two weeks longer. (Since the diseased
mice normally live only about four months, two weeks represented a significant
increase in life expectancy.)
In the current work, the hNT neurons
did not extend the lifespan of the ALS model mice, but the treatment did
slow their loss of movement. To quantitate how well the mice could move,
the Florida researchers injected cells into seven of the mutant mice with
signs of advanced ALS. Then, they measured the ability of each mouse to
walk across a beam without falling, to maintain their balance on a rotating
rod, or to extend their hind legs when suspended by the tail.
Although some of the transplanted
animals died soon after the operation, the one that survived kept its ability
to perform all of these tasks for three weeks longer than mice injected
only with an innocuous solution and another ALS mouse that received no
treatment. What's more, the hNT neurons survived in the animal's spinal
cord.
The work was partially funded by
Layton Bioscience of Sunnyvale, California, which owns rights to sell hNT
cells. Sanberg is a scientific advisor to the company.
Although the results are "very preliminary,"
the work is "important because it provides hope that alternative procedures
could give rise to therapeutics," says Jay Wang of the Carolinas Medical
Center in Charlotte, North Carolina.
In another recent study, also presented
here this week, a team led by Jeffrey Rothstein of Johns Hopkins University
showed that stem cells derived from human embryos incorporated themselves
into the spinal cord of African green monkeys with ALS-like symptoms. The
work was partly funded by the Geron Corporation, which owns sole rights
to sell therapies based on human embryonic stem cells.
Since earlier work demonstrated that
the cells helped rats with ALS symptoms regain strength in their hind legs,
the researchers are keeping an eye on the monkeys to see if the cells help
the monkeys regain motor skills.
See also:
Of
mice, men and motor neurons [Review]
Recombinant
proteins for neurodegenerative diseases: the delivery issue [Review]
Novel
drug development for amyotrophic lateral sclerosis [Review article]
Investigator: Svitlana Garbuzova-Davis
by Dan Ferber
SFN
2001 - Society for Neuroscience
Helen J. Newbery and Catherine M.
Abbott
Trends in Genetics, 2001, 17:10:S2-S6
Patrick Aebischer and Jean-Luc Ridet
Trends in Neurosciences, 2001, 24:9:533-540
Orest Hurko and Frank S. Walsh
Journal of the Neurological Sciences,
2000, 180:1-2:21-28
© Elsevier Science Limited
2000