Myelin Disorders: Causes and Perspectives of CMT Neuropathy

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J Mol Neurosci. 2006 Jan;28(1):77-88.

Myelin Disorders: Causes and Perspectives of Charcot-Marie-Tooth

Neuropathy.

Zu H 246 Rste GM, Prukop T, Nave KA, Sereda MW.

Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.

Charcot-Marie-Tooth (CMT) disease is a common hereditary neuropathy

that causes progressive distally pronounced muscle weakness and can

lead to life-long disability in patients. In most cases, the disorder

has been associated with a partial duplication of human chromosome 17

(CMT1A), causing 1.5-fold overexpression of the peripheral myelin

protein 22 kDa (PMP22). Increased PMP22 gene dosage results in

demyelination, secondary axonal loss, and neurogenic muscle atrophy.

Experimental therapeutic approaches based on the role of progesterone

and ascorbic acid in myelin formation recently have reached

preclinical proof-of-principle trials in rodents. It was shown that

progesterone receptor antagonists can reduce PMP22 overexpression and

clinical severity in a CMT1A rat model. Furthermore, ascorbic acid

treatment reduced premature death and demyelination in a CMT1A mouse

model.

Thus, basic research has opened up new vistas for the understanding

and treatment of hereditary neuropathies.