Gene Therapy Could Potentially Treat Rare Nervous System Disease

Niemann-Pick disease could be treated with gene therapy.

Investigators recently found that gene therapy could be a potential way to treat Neimann-Pick disease, type C1, which is caused by a faulty protein.

Neimann-Pick is a rare disease of the central nervous system that currently has no cure. It is characterized by a gene failing to remove waste cells (lipids and cholesterol) that eventually accumulate in the spleen, liver, and brain.

This waste cell build-up eventually causes intellectual and motor impairment, and deterioration of the affected organs. A majority of patients die in their teens, with many not living past 10-years-old. There are 3 different types of the disease: type A, type B, and type C.

The goal of the study, published by Human Molecular Genetics, was to correct the faulty gene in the cells and organs of mice models of the Neimann-Pick disease, type C1. Their main focus was to correct the gene in the brain to prevent cognitive and other associated impairment.

Investigators used adeno-associated virus serotype 9, a non-disease causing virus, to deliver normal NPC1 to the cells of the mice models. The virus containing NPC1 was able to cross the blood-brain barrier to deliver the gene to the brain and correct cell defects.

Mice had improved motor coordination, weight gain, and longevity after 1 injection compared with mice who did not receive gene therapy.

“We’re very encouraged by this preliminary work,” said investigator William J. Pavan, PhD. “The gene therapy is treating the root of the problem, the defective gene.”

Investigators said the gene therapy provided benefits similar to those seen with the experimental drug VTS-270, but the drug had to be given 3 times per week and did not provide a cure. They are now exploring a combination treatment option with VTS-270 and gene therapy to determine if it will improve the results seen with the individual treatments.

These findings may also provide insight into potential treatment options for other similar genetic disorders, including mucolipidosis IV, Batten disease, and Danon disease.

“Our work in NPC1 mice may help lead to human clinical trials and eventually FDA approval for gene therapy as a treatment for NPC1 disease,” said investigator Charles P. Venditti, MD, PhD. “For NPC1 patients, gene therapy could halt progression of the disease, improve the quality of their lives and, hopefully, increase the patient’s life span.”