New treatments for denervating diseases (CMT 1A)

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J Child Neurol. 2005 Mar;20(3):258-62.

New treatments for denervating diseases.

Pleasure D.

Children's Hospital of Philadelphia, 34th and Civic Center Blvd,

Philadelphia, PA 19104 USA.

There has been considerable recent progress in understanding

mechanisms by which gene mutations cause degeneration of motoneurons

and peripheral nerves. Novel therapies inspired by these insights

have begun to yield promising results in mouse models of these

genetic diseases. Among these have been the use of small molecules or

proteins to suppress gain-of-function mutations (eg, ascorbic acid

for Charcot-Marie-Tooth disease type 1A) or to restore enzyme

activities that are deficient because of loss-of-function mutations

(eg, treatment of Fabry's disease with recombinant alpha-

galactosidase or with low-molecular-weight alpha-galactosidase

chaperones and treatment of spinal muscular atrophy with

phenylbutyrate). Some of these therapies are already being tested in

humans. Equally exciting is the prospect that small molecules and

proteins will be identified that exert potent therapeutic effects in

a broad spectrum of inherited and acquired motoneuron and peripheral

nerve disorders.