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Transplanted neural stem cells slows als onset and progression in mouse models

20.12.2012
Promising new research provides evidence that ALS, amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, may be treatable using neural stem cells.

A consortium of researchers at multiple institutions, including the University of Massachusetts Medical School, Sanford-Burnham Medical Research Institute and Brigham and Women's Hospital, have shown that neural stem cells, when transplanted into the spinal cord of a mouse model with familial ALS, slow disease onset and progression while improving motor function, breathing and survival time compared to untreated mice. A summary of the studies was published online in Science Translational Medicine.

ALS is a progressive, neurodegenerative disorder affecting the motor neurons in the central nervous system. As motor neurons die, the brain's ability to send signals to the body's muscles is compromised. This leads to loss of voluntary muscle movement, paralysis and eventually respiratory failure. The cause of most cases of ALS is not known.

Approximately 10 percent of cases are inherited. Though investigators at UMass Medical School and elsewhere have identified several genes shown to cause inherited or familial ALS, almost 50 percent of these cases have an unknown genetic cause.

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. These cells can also rescue malfunctioning nerve cells and help preserve and regenerate brain tissue. But they've never before been studied extensively in a good model of adult ALS.

In 11 independent studies, the group, headed by Dr. Evan Snyder of the Burnham Institute, transplanted neural stem cells into the spinal cord of a mouse model of ALS. The transplanted neural stem cells benefited the mice with ALS by preserving the health and function of the remaining nerve cells.

Specifically, the neural stem cells promoted the production of protective molecules that spared remaining nerve cells from destruction. They also reduced inflammation and suppressed the number of toxin-producing and disease-causing cells in the host's spinal cord.

"It is striking that the stem cells improve motor neuron viability without generating new motor neurons. These findings encourage us to explore further the role of cell therapies in ALS," said Robert Brown, MD, DPhil, a co-author on the study and chair of neurology at UMass Medical School. A leading expert in ALS, Dr. Brown led the team that discovered the first gene linked to familial ALS, a protein anti-oxidant known as superoxide dismutase, or SOD1 in 1993.

This research was funded by Project ALS, California Institute for Regenerative Medicine, the U.S. National Institutes of Health (National Institute of Neurological Disorders and Stroke grants R21NS053935, 1RC2NS070342-01, 1RC1NS068391-01, R01NS050557-05, U01NS05225-03), U.S. Department of Veterans Affairs, Christopher Reeve Foundation/American Paralysis Association, Project ALS, P2ALS, Sanford Children's Health Research Center, Zinberg Foundation, ALS Therapy Alliance, ALS Association, Angel Fund, Al-Athel Foundation, Pierre L. deBourgknect ALS Research Foundation, and HeadNorth.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $250 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu.

Jim Fessenden | EurekAlert!
Further information:
http://www.umassmed.edu

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