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New UW study offers strategy for treatment of fatal nervous system disorder

Working with mice, University of Wisconsin-Madison researchers have developed the basis for a therapeutic strategy that could provide hope for children afflicted with Krabbe's disease, a fatal nervous system disorder.

Writing this week (Dec. 12, 2005) in the Proceedings of the National Academy of Sciences (PNAS), a team of researchers at the UW-Madison School of Veterinary Medicine describes experiments that effectively promoted the ability of defective cells to take up and utilize an enzyme that is essential for the maintenance of a critical sheathing of nerve fibers.

The work centers on devising strategies to treat inherited diseases of the nervous system in which cells fail to maintain myelin, a protective sheathing that envelops nerve fibers and acts like the insulation on an electric wire. Myelin ensures the effective transmission of the signals routinely conducted by the nervous system. For those afflicted with Krabbe's disease, the loss of myelin results in arrested motor and mental development, seizures, paralysis and, ultimately, death.

The Wisconsin experiments, led by Ian Duncan, a UW-Madison professor of medical sciences who is an expert on diseases of myelin, explored how cells obtained from a mouse model of Krabbe's disease could be reinvigorated by replacing a missing enzyme, and thus allow the healthy maintenance of myelin.

In the case of Krabbe's disease, myelination begins normally in early development. But the absence in myelin-forming cells of a key enzyme known as galactocerebrosidase leads to the death of the cells and, subsequently, the loss of myelin. "Our hypothesis was that if you provided the (flawed) myelinating cells with the enzyme, the cells would maintain the myelin as healthy cells would," says Duncan, the senior author of the PNAS paper who planned and conducted the experiments with lead author Yoichi Kondo, a postdoctoral fellow working in Duncan's lab.

Simply supplying the enzyme directly to the brai
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12-Dec-2005


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