NT3 Gene Therapy for CMT1A Benefits Mice

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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.