Hereditary neuropathy: recent advance

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Rinsho Shinkeigaku. 2008 Nov;48(11):1019-22.

Hereditary neuropathy: recent advance (article in Japanese)

Nakagawa M.

Department of Neurology, Graduate School of Medical Science, Kyoto

Prefectural University of Medicine.

Hereditary neuropathies are classified into Charcot-Marie-Tooth

disease (CMT), familial amyloid polyneuropathy (FAP), hereditary

motor neuropathies (HMN) and hereditary sensory (and autonomic)

neuropathies (HSAN).

CMTs are furthermore classified into demyelinating neuropathies

(CMT1), axonal neuropathies (CMT2) and intermediate form. Duplication

of PMP22 (CMT1A) accounts for about 70% of CMT1 and MFN2 mutations

account for 25% of CMT2.

Genes involved in phosphoinositide regulation cause CMT4; MTMR2

mutation in CMT 4B1 and MTMR13/SBF2 mutation in CMT4B2. In addition

to these genes, FIG4, which is a causative gene of pale tremor mouse,

is newly identified as a gene for CMT4J.

MFN2 and GDAP1 cause CMT2 or CMT4. These genes regulate mitochondrial

fusion and fission. Altered axonal mitochondrial transport is

suggested as the pathogenesis of the CMT.

In animal model with pmp22 duplication, ascorbic acid seems to be

effective to prevent disease progression.

Nationwide trial of ascorbic acid therapy for CMT1A is now ongoing by

the intractable neuropathy study group.

Curcumin treatment educes apoptosis of cells that express PMP22 point

mutation and partially mitigates the severe neuropathy phenotype of

Trembler-J mouse model in a dose-dependent manner.

Curcumin treatment may have a potential therapeutic role in CMT with

PMP22 point mutation in humans. The high throughput system of

diagnosis for CMT has been developed by employing a resequencing

array system.