Molecular genetics, biology, and therapy for inherited peripheral neuropathies

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Neuromolecular Med. 2006;8(1-2):1-2.

Molecular genetics, biology, and therapy for inherited peripheral

neuropathies.

Timmerman V, Lupski JR, De Jonghe P.

Peripheral Neuropathy Group, Department of Molecular Genetics,

Flanders Interuniversity Institute for Biotechnology, University of

Antwerp, Antwerpen, Belgium; Laboratory of Neurogenetics, Institute

Born-Bunge, University of Antwerp, Antwerpen, Belgium.

This issue reviews the most recent findings in the molecular

genetics, biology, and therapy for inherited peripheral neuropathies.

The best-known form is Charcot-Marie-Tooth disorder (CMT), an

inherited neuropathy first described in 1886 (Charcot and Marie,

1886; Tooth, 1886). Most patients have progressive weakness and

wasting of foot and hand muscles. Sometimes patients need walking

aids or rarely become wheelchair dependent even at a young age. The

clinical variability and genetic heterogeneity in CMT often poses

difficult diagnostic challenges.

Treatment is currently supportive and a therapy that fundamentally

alters the course of CMT neuropathy is still lacking but recent

studies in animal models show promising results.

A better understanding of the molecular architecture of the

peripheral nerve, the functional pathways, the myelination process,

and the complex interaction between the myelinating Schwann cells,

the axon, and muscle is crucial to identify targets for therapeutic

interventions.

The identification of loci, genes, and disease-causing mutations

involved toward inherited peripheral neuropathies is the first step

toward this understanding, and in the mean time provide tools for

molecular genetic diagnosis. Genotype/phenotype correlations guide

the selection of specific mutations suitable for functional analysis

in cellular and animal models. These models are instrumental in the

search for therapies, as it was very recently demonstrated in both a

CMT rat and mouse model. T

he knowledge gained from the molecular genetic and biological

research of inherited peripheral neuropathies will also help to make

progress in the study of acquired neuropathies. Some of these

neuropathies are often therapy-resistant and have a profound

influence on the quality of life of the affected individuals.