Human Stem Cells Help Rats to Fend Off Lou Gehrig's Disease
By Rob Waters
Oct. 15 (Bloomberg) -- Neural stem cells transplanted into
the spinal cords of rats from a human fetus slowed onset of a form of Lou Gehrig's
disease, a condition that attacks the nerve circuits that control movement.
Researchers placed the cells in rats genetically
engineered to develop a form of the disease, also know as amyotrophic lateral
sclerosis or ALS. The rodents with the cells were slower to show symptoms such
as weight loss and diminished strength, and lived about 11 days longer over a
30-month life span.
The finding suggests stem cells can be grafted into
damaged nervous systems for a clinical benefit, contradicting the belief of
many scientists. It may also eventually offer hope to about 5,600 people in the
``The dogma was that the spinal cord can not make neurons,
or allow engrafted cells to become neurons,'' said Vassilis Koliatsos, the
Johns Hopkins School of Medicine neurologist who led the study, in an Oct. 12
telephone interview. ``The assumption was also that because this is a toxic
environment where motor neurons are dying, the cells would die.''
These assumptions ``are increasingly proven wrong'' by
this research and other recent studies, he said. Koliatsos's study was
published today in the journal Transplantation.
The transplanted cells, which developed into neurons, or
nerve cells, formed connections to existing neurons that had been damaged by
the disease and were able to convey information through electrical signals and
deliver proteins to help nourish the sick cells, Koliatsos said.
Neuralstem Inc.
The researchers used a line of neural stem cells developed
by Neuralstem Inc., a closely held biotechnology company based in
The stem cells, taken from an area near the developing
spinal cord of the fetus, have the theoretical ability to develop or
differentiate into any of three cell types found in the nervous system. The
cells were kept alive in culture and chemically manipulated to keep them from
differentiating.
The researchers exposed the spinal cords of the rats and
used a tiny micropipette to inject cells. Rats in one group were given about
400,000 living neural stem cells; another control group was injected with dead
cells.
The rats that got the live cells began losing weight at
about 59 days on average, a week later than the rats in the control group. When
made to walk an uphill plank as a strength test, the cell-treated rats
performed better over a longer period of time. They also lived to about 86
days, 11 days longer than the control rats.
70 Percent Developed
When the rats were examined after their deaths, the
researchers found that more than 70 percent of the transplanted stem cells had
developed into nerve cells, and that many grew endings that connected to other
cells, allowing them to transfer nerve impulses that direct muscular action and
movement.
``These cells became neurons and they also made
connections to sick neurons,'' he said. ``If you make connections to sick
neurons, you close the circuit, you give them information.''
The connections allowed needed proteins and growth factors
produced by the new neurons to pass to the damaged cells. This may help solve a
problem that has vexed researchers. When scientists have delivered these
proteins and growth factors, also known as trophic factors, using drugs, they
reached unwanted targets and caused side effects, Koliatsos said.
`Delivers the Goods'
``You use the stem cell as a very complex biological
structure or machine that manufactures and sends these trophic factors where
they ought to be given,'' he said. ``It delivers the goods right on target.''
In this experiment, stem cells were injected in the
portion of the spinal cord that controls the lower body. The next step, which
Koliatsos has already begun working on, is to deliver the cells to the part of
the spinal cord that controls upper body motion, including chest wall expansion
and breathing.
``We need to do that, see if it's well tolerated and see
if we can extend their survival longer,'' Koliatsos said. After that, he said,
he'll start thinking about how to study this type of treatment in people.
About 30,000 Americans have Lou Gehrig's disease,
according to the ALS Association. The disease begins with weakness in the arms
and legs, and progresses to paralysis as motor neurons are damaged.
The study was funded by the National Institutes of Health,
the Muscular Dystrophy Association and the university's
To contact the
reporter on this story: Rob Waters in
Last Updated: October 15, 2006 00:58 EDT