Myelin disorders: Causes and perspectives of Charcot-Marie-Tooth neuropathy.
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.
Meyer zu Hörste
Gerd
G
Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
Prukop
Thomas
T
Nave
Klaus-Armin
KA
Sereda
Michael W
MW
D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D004594:Electrophysiology; D018628:Gene Dosage; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use
D013256:Steroids