Transplanted Immune Cells Prolong Life In ALS Studies
Main Category: Neurology / Neuroscience News
Article Date: 23 Oct 2006 - 0:00am (PDT)
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Researchers at the Methodist Neurological Institute (NI) have demonstrated that the immune cells of the spinal cord and brain contribute significantly to prolonging survival in a model of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that results in paralysis and eventual death, according to a study published today in Proceedings of the National Academy of Sciences U.S.A.
By performing bone marrow transplants in mice that are born without immune systems, transplanted cells slowed the loss of motoneurons and increased life expectancy by 40 percent.
The most common inherited form of ALS, also known as Lou Gehrig's disease, is caused by dominant mutations in a gene known as SOD1. NI scientists showed that in a mouse model of inherited ALS, normal microglia derived from transplanted bone marrow protected motoneurons in the spinal cord. Motoneurons are the cells that stimulate skeletal muscle movement. This study also demonstrated that microglia expressing mutant SOD1 were more toxic and contributed to motoneuron injury.
What the study shows is through bone marrow transplants in this animal model of ALS, we replaced spinal cord mutant SOD1 expressing microglia, which are predominantly toxic, with normal microglia, which are more protective, said Dr. David R. Beers, first author on the paper and a lead ALS researcher at the NI.
Dr. Jenny S. Henkel, co-first author on the paper, said, With the recognition that cells of the immune system can contribute to motoneuron protection, other stem cell strategies, including those engineered to produce protective factors, could lead to novel treatments for ALS patients.
Microglia are the innate immune cells of the central nervous system that play numerous roles in protecting and injuring neurons. One mission of the NI scientists is to determine how and when protective microglia become harmful to motoneurons and how to transform these cells back into protective microglia. In addition to ALS, microglia are thought to play major roles in other neurodegenerative disorders such as Alzheimer's disease, dementia, and multiple sclerosis.
We've long supported the concept that neurons do not die by themselves, but that the inflammatory process plays a significant role in motoneuron injury, according to Dr. Stanley H. Appel, chairman of the department of neurology and medical director of the MDA/ALS Clinic at the Methodist NI. By establishing that these transplanted cells slowed motoneuron loss and prolonged survival, our research findings could have a significant impact on how we approach treatment in patients with ALS, and how we move forward with other ALS research. Our continued ALS research is immensely important because an estimated 30,000 people throughout the U.S. have ALS and 5,000 new cases are diagnosed each year.
In the majority of ALS cases, there is no known cause. Approximately 10 percent of all ALS cases are inherited.
Appel holds the Peggy and Gary Edwards Distinguished Endowed Chair for the Treatment and Research of ALS. The research presented in PNAS was supported by grants from the National Institutes of Health (NIH), the Muscular Dystrophy Association and The Houston Endowment Inc.
About the Methodist Neurological Institute
The Methodist Neurological Institute houses the practice and research activities of the departments of neurology, neurosurgery, neuroradiology, neuro-oncology and neuro-rehabilitation of The Methodist Hospital. The close collaboration between these departments offers patients the most advanced treatment options available. The mission of the NI is to advance the discovery of the origins, mechanisms and treatment of neurological disease and to provide comprehensive care for patients with disorders and injuries of the brain and spinal cord.
The Methodist Hospital is one of the nation's largest private, non-profit general hospitals. Methodist is primarily affiliated with Weill Medical College of Cornell University and New York Presbyterian Hospital. The hospital is also affiliated with the University of Houston.
Methodist is ranked among the country's top centers in six specialties in U.S News & World Report's 2006 America's Best Hospitals issue. The hospital ranked in more specialties than any other hospital in Houston, and is 10th on the list for neurology and neurosurgery.
For more on the Methodist Neurological Institute, visit http://www.methodistneuroinstitute.com
Methodist Hospital, Houston
6565 Fannin St.
Houston, Tx 77030