Gene Therapy Shows Promise for Niemann-Pick Disease Type C1

Niemann-Pick disease is a rare and fatal disorder of the central nervous system (the brain and spinal cord) that has no cure.

For the first time, NIH researchers have demonstrated in mice that gene therapy may be the best method for correcting the single faulty gene that causes Niemann-Pick disease, type C1 (NPC1). The gene therapy involved inserting a functional copy of the NPC1 gene into mice with the disease; the treated animals were then found to have less severe NPC1 symptoms. The study, led by researchers at NHGRI and NICHD, was published Oct. 26 in the journal Human Molecular Genetics.

Niemann-Pick disease is a rare and fatal disorder of the central nervous system (the brain and spinal cord) that has no cure. The disease occurs when a faulty housekeeping gene fails to remove cell waste, like lipids and cholesterol. The accumulation of waste in the spleen, liver and brain causes progressive deterioration in intellectual and motor functions. It also shortens patients’ lives, as people with Niemann-Pick disease typically die in their teens. 

The researchers’ goal was to correct the faulty NPC1 gene in as many cells and organs as possible, with a strong focus on the brain. To do this, they used a non-disease-causing virus called the adeno-associated virus serotype 9 to transfer functioning NPC1 to the cells. The AAV9 containing a functioning NPC1 gene successfully crossed the blood-brain barrier, reaching cells in the brain and elsewhere. Once inside cells, the normal NPC1 gene was then able to make the functional NPC1 protein to correct the cell defects. 

With a single injection, mice showed improvements in motor coordination, weight gain and longevity compared to those without this gene therapy. 

“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 Dr. Charles Venditti, senior investigator in NHGRI’s Medical Genomics and Metabolic Genetics Branch. “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.”