For the first time, researchers have enticed transplants of embryonic stem cell-derived motor neurons in the spinal cord to connect with muscles and partially restore function in paralyzed animals. The study suggests that similar techniques may be useful for treating such disorders as spinal cord injury, transverse myelitis, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy. The study was funded in part by the National Institutes of Health's National Institute of Neurological Disorders and Stroke.
The researchers, led by Douglas Kerr, M.D., Ph.D., of The Johns Hopkins University School of Medicine, used a combination of transplanted motor neurons, chemicals capable of overcoming signals that inhibit axon growth, and a nerve growth factor to attract axons to muscles. The report is published in the July 2006 issue of Annals of Neurology.
In the study, Dr. Kerr and his colleagues cultured embryonic stem cells from mice with chemicals that caused them to differentiate into motor neurons. Just before transplantation, they added three nerve growth factors to the culture medium. Most of the cells were also cultured with a substance called dibutyrl cAMP (dbcAMP) that helps to overcome axon-inhibiting signals from myelin, the substance that insulates nerve fibers in the spinal cord.
Previous studies have shown that stem cells can halt spinal motor neuron degeneration and restore function in animals with spinal cord injury or ALS. However, this study is the first to show that transplanted neurons can form functional connections with the adult mammalian nervous system, the researchers say. They used both electrophysiological and behavioral studies to verify that the recovery was due to connections between the peripheral nervous system and the transplanted neurons.
While these results are promising, much work remains before a similar strategy could be tried in humans, Dr. Kerr says. The therapy must first be tested in larger animals to determine if the nerves can reconnect over longer distances and to make sure the treatments are safe. There currently is no large-animal model for motor neuron degeneration, so Dr. Kerr's group is working to develop a pig model. Researchers also need to test human embryonic stem cells to learn if they will work in the same way as the mouse cells. It has only recently become possible to grow motor neurons from human embryonic stem cells, Dr. Kerr adds. However, if the future studies go well, this type of therapy might eventually be useful for spinal muscular atrophy, ALS, and other motor neuron diseases.
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