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Brain Stem Cells Reverse Myelin Deficiency in Mice
Date:6/5/2008

onditions like adrenoleukodystrophy, the condition featured in the movie, Lorenzo's Oil.

In this study, Goldman and his team used "shiverer" mice, whose congenital lack of myelin basic protein causes them to shake and seize uncontrollably, giving them their name. They typically die by 5 months of age.

The shiverer mice were crossed with immunodeficient mice, so they would not reject the GPC transplant, and split into three treatment groups; 59 received no treatment, 29 received injections of buffer into five different locations in the brain shortly after birth, and 26 received injections of GPCs.

By about 130 days after birth, all 88 control mice died. But six of 26 transplanted animals survived at least 160 days, and four lived over a year. Behaviorally and physiologically, these survivors appeared largely cured, and post-mortem analysis of these animals' brains and spinal cords demonstrated why.

"The entire central nervous system had remyelinated and looked normal in terms of structural configuration of the myelination, both at the microscopic and submicroscopic level, and at the behavioral level," Goldman said.

In other words, from five separate injection sites, the GPCs migrated throughout the central nervous system, differentiated into oligodendrocytes, and began producing myelin.

The researchers then assessed the physiological effect of that remyelination, by measuring the speed of nerve transmission along remyelinated axons. They observed velocities on par with those of normal mice.

"That is proof in principle that putting glial progenitors in a brain like this will at least partially remyelinate the brain, and do so functionally," said James Goldman.

Though this study involved a congenital pediatric disorder, Steven Goldman said his goal is to apply the technique to adult diseases like multiple sclerosis. For now, his team is working to understand why most transplanted
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