Researchers are investigating whether treatments for other disorders might benefit people with a newly identified type of Charcot-Marie-Tooth disease (CMT) that may be a common recessive form of hereditary neuropathy.
They are inviting people diagnosed with CMT but with no clear disease-causing mutation to help by joining a registry whose data are supporting further work. Genetic testing for this subtype will be offered to those who register.
“This remarkable discovery has been possible because of CMT patients participating in our genetic studies,” Stephan Züchner, MD, PhD, the senior author of study describing the new subtype, said in a release posted by the Hereditary Neuropathy Foundation.
Mutations in the sorbitol dehydrogenase gene (SORD) cause this new CMT subtype. The SORD enzyme, whose production derives from this gene, converts sorbitol into fructose via a pathway that has been implicated in diabetic peripheral neuropathy — or diabetes-related damage to nerve cells outside the central nervous system.
Some medications approved for diabetic neuropathy also target SORD, and may prove effective in treating this CMT type. Because these compounds have already undergone Phase 1 safety and toxicity testing on their way to being approved, it may be possible to proceed directly to Phase 2 trials for CMT.
As a recessive disorder, a person must inherit a faulty SORD copy from each parent to acquire the new CMT subtype. The researchers estimate that over 60,000 people worldwide — including 3,000 to 5,000 in the United States — might have this CMT subtype, making it the most common type of recessive CMT.
Züchner and his colleagues experimented with SORD in flies, an animal frequently used in neurological studies. They saw that the loss of SORD in the insects caused nerve degeneration that affected movement. Treating the flies with two known compounds, epalrestat (approved in Japan to treat diabetic neuropathy) and ranirestat, reduced the buildup of sorbitol and eased the flies’ motor symptoms.
The Hereditary Neuropathy Foundation is now supporting the development of a SORD rat model for testing these candidate therapies in studies that might lead to trial in CMT patients. Work is underway, and the foundation plans to post periodic updates.
“For the next phase we are committed to offering free SORD gene testing to screen undiagnosed CMT patients in the hopes of more patients receiving a confirmed CMT diagnosis as well as identifying more patients in preparation of clinical trials,” Züchner said.
Anyone interested in participating in this testing is encouraged to contact [email protected], and to join the Global Registry for Inherited Neuropathies, a worldwide patient registry. The registry is currently offline but those who register will be notified when it returns.
To be eligible for screening, an individual must have a CMT diagnosis, but possibly an unconfirmed one because could not conclusively identified the responsible gene, and have parents without CMT symptoms, although a sibling may have such symptoms.
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