NT3 Gene Therapy for CMT1A Benefits Mice

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NT3 Gene Therapy for CMT1A Benefits Mice

by Margaret Wahl on April 21, 2010

http://quest.mda.org/news/nt3-gene-therapy-cmt1a-benefits-mice

Mice with a disorder resembling type 1A Charcot-Marie-Tooth (CMT1A) disease that

received a single intramuscular injection of genes for the protein neurotrophin

3 (NT3) showed improvements in grip strength, ability to stay on a rotating rod,

and strength of nerve signals, investigators reported April 15, at the 2010

meeting of the American Academy of Neurology, held in Toronto.

Earlier studies had tested subcutaneous (under the skin) injections of the NT3

protein, in both mice and humans, and found hints of effectiveness. However, the

current study shows that muscle tissue can provide a reservoir for the NT3 genes

and secrete the NT3 protein, providing a more durable treatment, the researchers

said.

Zarife Sahenk, a professor of pediatrics, neurology and pathology at Ohio State

University in Columbus, presented the findings, saying the promising results

offer potential for gene therapy for CMT1A — and possibly for other CMT forms,

of which there are about 30.

About the new findings

Mice with a mutation in the PMP22 gene, the same gene involved in human CMT1A,

received a single injection into an upper leg muscle of NT3 genes encased in

type 1 adeno-associated viral delivery vehicles (AAV1 vectors). The experiments

were conducted in the Gene Therapy Center at Nationwide Children's Hospital in

Columbus.

NT3 is a naturally occuring protein that promotes nerve growth and survival.

Twenty weeks after the injection, the investigators found the mice that received

the treatment had stronger signals from the sciatic nerve to the leg muscles,

larger lower-leg muscle fibers, better grip strength in their back legs and

better ability to stay on a rotating rod than did mice in the untreated

(control) group.

Forty weeks after the treatment, the increases in nerve signals and performance

on the rotating rod were even greater.

Meaning for people with CMT1A

The study means that NT3 gene therapy in general, and intramuscular delivery of

the therapy in particular, has some potential for treating people with CMT1A and

possibly other types of CMT, because NT3 is thought to be good for nerve fibers

in general.