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Genetic basis of hereditary nerve disorder revealed

DURHAM, N.C. -- A major form of one of the most prevalent inherited neurological disorders in humans, Charcot-Marie-Tooth disease (CMT), stems from an abnormality in the cellular powerhouses, or mitochondria, that fuel the nerves required for muscle control, suggests new findings by neurogeneticists at the Duke Center for Human Genetics and their international colleagues. The unexpected discovery could open new research pathways to understanding an array of diseases of the peripheral nervous system, as well as treatments for CMT, the researchers said.

In seven families with a form of the degenerative nerve disorder CMT type 2A, the team discovered that defects in a gene critical to mitochondrial movement, known as mitofusin 2, underlies the disease symptoms. Restoring the lost gene function through gene therapy might ultimately serve as an effective treatment for the disorder, which currently has no cure, the researchers reported in the April 4, 2004, issue of Nature Genetics.

CMT affects people of all races, including 150,000 Americans. Hallmarks of CMT include weakening of the feet and hands that gradually extends to the legs and arms. The only treatments now available to patients with the disease include physical therapy and moderate activity to maintain muscle strength. Patients often rely on leg braces and, in some cases, become wheelchair-dependent.

While defects in multiple genes are known to underlie various forms of CMT, the current finding uncovers a whole new mechanism of action that can cause disease by damaging mitochondria, said lead author of the study Stephan Zchner, M.D., of the Duke Center for Human Genetics and the department of neuropathology at the University Hospital Aachen in Germany.

"Mitochondria must link into constantly shifting networks through fusion and fission in order to provide the energy required for neurons to fire and stimulate muscles to move," said Zchner. "Mitofusin 2 is critical to that p
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-684-4148
Duke University Medical Center
4-Apr-2004


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