New Treatments for Denervating Diseases

Abstract

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.

Charcot‐Marie‐Tooth neuropathy type 1A combined with Duchenne muscular dystrophy

“…CMT1A, the most common form, is autosomal dominantly inherited and caused by the duplication of a 1.5‐Mb portion of chromosome 17 containing the PMP22 gene (peripheral myelin protein 22) located within the region 17p11.2‐p12. The affected individual has three instead of two functional copies of the PMP22 gene [1–4]. PMP22 overexpression leads to impaired myelination of peripheral nerves resulting in slowly progressive distal demyelinating sensorimotor polyneuropathy and the typical CMT phenotype.…”

The Silver Jubilee: Journal of Child Neurology Turns 25

“…The annual Carrell-Krusen Symposium at the Texas Scottish Rite Hospital for Children in Dallas, begun in 1977 by Jay Cook and directed after 1990 by Susan Iannaccone, had been only a small regional meeting of Muscular Dystrophy Association (MDA) clinical directors and staff. I suggested publishing the meeting abstracts 168 in the Journal of Child Neurology (beginning in 1994, along with the lecture by the Carrell-Krusen visiting professor [169][170][171][172][173][174][175][176][177][178][179] ) and developing a brochure with a distinctive logo (volume10, number 4, July 1995, page 342) to advertise this arrangement and thereby increase the national visibility for, and attendance at, the meeting. That relationship lasted through 2006, when the Carrell-Krusen Symposium developed a new partnership with the Journal of Clinical Neuromuscular Disease.…”