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17 July 2008

Research: "The Myelin Project" - Autism and Stem Cells

The exciting work of researchers funded by The Myelin Project, whose goal is to remyelinate the human central nervous system, may someday have benefits for autistic children. Only time will tell if a specific area of damaged neurons can be found and potentially repaired with stem cells.

The first human trial, conducted by Dr. Timothy Vollmer at Yale University School of Medicine, will attempt to transplant myelin-forming Schwann cells into the brains of five patients with multiple sclerosis. The cells will be obtained from the sural nerves of the patients themselves. Although Schwann cells normally produce myelin in the peripheral nervous system, several recent experiments conducted on rodents and cats have shown these cells have the ability to remyelinate in the CNS as well.

While multiple sclerosis is a long way from autism, there is discussion of anti-myelin antibodies in autism, and there is talk of inflammatory processes involving myelin. Whether this technology can help autism if it works for multiple sclerosis is anybody's guess, but it's exciting to wonder about.

The Myelin Project funds a Cell Culture Unit at the University of Wisconsin-Madison, where Dr. Su-chun Zhang continues to generate cultures with ever-higher percentages of human oligodendrocyte precursors (OPs). Oligodendrocytes are the cells that normally myelinate the CNS. If obtainable in sufficient quantity, they would provide an alternative to Schwann cells for transplantation. The Unit has developed a method to track transplanted OPs by MRI, labeling the cells with iron particles. In another recent experiment, Dr. Baron-Van Evercooren and colleagues were able to remyelinate as many as 55% of the nerves in monkey spinal cord lesions by transplanting the monkeys' own Schwann cells. These initial positive results, however, have not been confirmed in subsequent attempts. She suspects that the viral labels she used to distinguish the transplanted cells caused them to die. She is trying again without viral labeling. If successful, this experiment would prove that CNS remyelination is feasible in higher animals.

Several researchers funded by The Myelin Project have injected myelin-forming cells into the ventricles of the brain of experimental animals and have shown that these cells were transported by the cerebrospinal fluid to all regions of the brain. This makes it more likely that injected cells will travel to where the myelin needs to be repopulated.

The Myelin Project has funded Dr. Oliver Br½stle of the University of Bonn, Germany, and Dr. Evan Snyder of Harvard University to work with neural stem cells (NSC). These are self-renewing, multipotent cells, capable of differentiating into the major types of neural cells, including oligodendrocytes. One of their most potentially beneficial properties is their tendency to respond to signals in the CNS environment. In CNS diseases, these signals guide the cells to damaged areas. Second, they prompt them to differentiate into the specific cell type needed for the repair -- neurons in nerve diseases like Parkinson's and oligodendrocytes in myelin disorders like the leukodystrophies and multiple sclerosis.

NSCs are typically of fetal origin, but have also been found in the adult brain. NSCs can be multiplied in culture indefinitely as an "immortal" cell line. They could eventually provide an inexhaustible source of myelin-forming cells, eliminating the need for obtaining them from fresh tissue. Several research centers are now testing human NSCs to verify their safety and in particular to rule out any risk of their becoming cancerous. If this testing concludes favorably, then prospective myelin repair strategies could take a two-fold approach. NSCs would be injected into the ventricular system where the cerebrospinal fluid would circulate them to all parts of the CNS. Local signals would then come into play, guiding the cells to the specific demyelinated areas.

The Myelin Project has also funded Dr. Robin Franklin of the University of Cambridge to study olfactory ensheathing cells, a third type of myelin-producing cell. He has perfected a technique for demyelinating the area of rat brain connecting the cerebellum with the brain stem. He subsequently remyelinated the area by transplanting rat Schwann cells, which adds to the body of evidence in favor of Schwann cell transplantation as a way of repairing CNS myelin lesions.

The Myelin Project has also funded Dr. Inderjit Singh of the Medical University of South Carolina to study the use of Lovastatin in the treatment of myelin disorders. The drug corrects the biochemical defect of adrenoleukodystrophy, lowering the levels of very long chain fatty acids in plasma. Preliminary studies with an animal model of MS have confirmed Lovastatin's ability to block the induction of cytokines, substances responsible for the inflammation of the CNS. We know that the levels of very long chain fatty acids and of some cytokines are elevated in autism. I am wonderijng already if Lovastatin might be worth trying for children with documented elevated very long chain fatty acids and elevated cytokines.

These studies present exciting possibilities for the future for treating neurodegenerative diseases. They may eventually have relevence for such diverse conditions as autism, cerebral palsy, and CNS vaccine damage syndromes. Time will tell.

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