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24/09/08
T-cells show promise for MND/ALS, neurodegenerative disease therapies
HOUSTON—(Sept. 22, 2008)—A type of white blood cell that is important to the immune system may provide hope for future new therapies for amyotrophic lateral sclerosis (ALS), as well as other neurodegenerative diseases, according to a study published online today in the Proceedings of the National Academy of Sciences.Researchers at The Methodist Hospital in Houston have shown that restoring functional T-cells, an immune system white blood cell, in a mouse model of ALS slows disease progression. T-cells play a critical role in protecting brain cells by enhancing the protective functions of supporting cells of the brain and spinal cord called glia. Of the ALS cases caused by genetic factors, about 10 percent have a mutation in a gene called superoxide dismutase 1, or SOD1, which mops up the free radicals that damage cell function.“In animal models of ALS, we and others have previously shown that reducing the levels of mutant SOD1 protein in glia slows the progression of the disease,” said Dr. Stanley H. Appel, last author and chairman of Neurology at Methodist. “However, in our current report, we demonstrate an alternative approach. In ALS mice with functional immune cells called CD4+ T-cells, the progression of the disease is again slowed and survival increased.”Co-lead authors Drs. David R. Beers and Jenny S. Henkel head the team of Methodist neurodegenerative disease scientists working with Appel, who also leads Methodist’s MDA/ALS Clinic and Research Center. Their findings show the disease could be slowed in these mice if they received a bone marrow transplant and were able to produce T-cells again.“It has been known for some time that T-cells are present at sites of injury in ALS patients as well as in mouse models of ALS, and until now, the role of these cells was unknown,” said Beers. “This study demonstrates that T-cells, possibly CD4+ T-cells, through their interaction with microglia and astroglia, are protecting the cells in the spinal cord that cause muscle movement. It is now critically important to understand how T-cells provide this neuroprotection.”“We’re currently looking at the sub-population of CD4+ T-cells that are providing this protection,” said Henkel. “These cells may eventually provide a readily accessible target for therapeutic intervention not only for ALS but other neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases.”ALS is a neurodegenerative disease caused by loss of the motor neurons that control all voluntary movement.This study was supported by the National Institutes of Health and the Muscular Dystrophy Association. It will be published in the Oct. 7 print issue of PNAS.