Results from 11 independent Amyotrophic lateral sclerosis research
studies are giving hope to the ALS community—showing for the first time that
the fatal disease may be treatable.
Researchers say progress treating
ALS, also known as Lou Gehrig’s Disease) may be made by targeting new
mechanisms revealed by neural stem cell-based studies.
“This significant research will
help us better understand the mechanisms underlying motor neuron diseases,”
said Yang (Ted) Teng, HMS associate professor of surgery at Brigham and
Women's Hospital and a
study's co-lead author. Teng is also director of the Spinal Cord Injury and Stem Cell
Biology Research Laboratory in the Department of Neurosurgery at
Brigham and Women’s Hospital.
The research studies were
conducted at Brigham and Women’s Hospital, Boston
Children’s Hospital,
Sanford-Burnham Medical Research Institute, UMass Medical School, Johns Hopkins
University, SUNY-Syracuse, Columbia University and VA Boston Healthcare System.
ALS causes nerve cells in the
spinal cord to die, eventually taking away a person's ability to move or even
breathe. A decade of research conducted at multiple institutions,
however, shows that when neural stem cells were transplanted into multi-levels
of the spinal cord of a mouse model with familial ALS, disease onset and
progression slowed, motor and breathing function improved and treated mice
survived three to four times longer than untreated mice.
A summary of the findings from
all 11 studies publishes was published online in December inScience
Translational Medicine.
The transplanted neural stem
cells help by producing factors that preserve the health and function of the
host's remaining nerve cells. They also reduce inflammation and supress
the number of disease-causing cells in the host's spinal cord.
“This work sheds new light on
detrimental roles played by non-neuronal cells in triggering motor neuron death
and these events should be targeted for developing more effective therapeutics
to treat ALS,” Teng said.
The transplanted neural stem
cells benefited the mice with ALS by boosting the health and function of their
remaining nerve cells. The neural stem cells also reduced inflammation
and suppressed the number of disease-causing cells in their spinal cords.
The neural stem cells did not replace deteriorating nerve cells.
Researchers observed improved motor performance and respiratory function in the
treated mice.
The neural stem cell transplant
also slowed the disease's progression. Twenty-five percent of the treated
ALS mice in the study survived for one year or more -- roughly three to four
times longer than untreated mice.
“This is not a cure for ALS,”
said Dr. Teng, who is one of the principal investigators of Project ALS’ consortium
project. “But it shows the potential that mechanisms used by neural stem
cells in our study have for improving an ALS patient’s quality of life and
length of life.”
Neural stem cells are the
precursors of all brain cells. They can self-renew, making more neural
stem cells, and differentiate, becoming nerve cells or other brain cells.
The cells can also rescue malfunctioning nerve cells and help preserve and
regenerate host brain tissue.
The transplanted neural stem
cells helped the ALS mice, but not for the obvious reason—not because they
became nerve cells, replacing those missing in the ALS spinal cord. The biggest
impact actually came from a series of other beneficial neural stem cell
activities. It turns out neural stem cells produce protective molecules. They
also trigger host cells to produce their own protective molecules. In turn,
these factors help spare host nerve cells from further destruction.
Then a number of other positive
events take place in treated mice. The transplanted normal neural stem cells
change the fate of the host’s own diseased neural stem cells -- for the better.
This change decreases the number of toxin-producing, disease-promoting cells in
the host’s spinal cord. Transplanted neural stem cells also reduce inflammation.
Researchers discovered that cell
replacement played a surprisingly small role in the impressive clinical
benefits. Rather, the stem cells changed the host environment for the better
and protected the endangered nerve cells.
The research studies were
primarily funded by Project ALS, the California Institute for Regenerative
Medicine, the National Institute of Neurological Disorders and Stroke the
Christopher Reeve Foundation/American Paralysis Association, the Sanford
Children’s Research Center, the A-T Children’s Project and the Zinberg
Foundation.
Additional support to Dr. Teng
was provided by a VA Biomedical Research and Development Grant, a VA
Rehabilitation Research and Development Grant, and an NIH R21 grant. (Lou
Gehrig’s Disease) research studies are giving hope to the ALS community --
showing for the first time that the disease may be treatable by targeting new
mechanisms revealed by neural stem cell-based studies.
Harvard Medical School
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