NHGRI Researchers Achieve Successful Gene Therapy in Mice

NHGRI Researchers Achieve Successful Gene Therapy in Mice

Propionic acidemia, a potentially fatal metabolic disorder that affects as many as one in 50,000 American babies, can be treated in mice using gene therapy, according to a National Human Genome Research Institute (NHGRI) study published in the October 2010 advance online issue of Human Gene Therapy. The finding paves the way for patients with this pediatric metabolic disorder to be treated using gene therapy in the future, according to senior author Charles Venditti M.D., Ph.D., investigator in NHGRI's Genetics and Molecular Biology Branch.

Newborns with propionic acidemia can die if not immediately diagnosed and treated with a special low protein diet and metabolic supplements. Patients sometimes receive liver transplantation to improve the symptoms of this disease. However, they still experience numerous effects from the disorder.

The disease is related to another condition called methylmalonic acidemia (MMA); the enzymes that malfunction in both disorders are located in the same metabolic pathway. Using the same methods previously employed to successfully treat mice with MMA, the researchers used a recombinant adeno-associated virus (AAV) — a gene delivery agent that is not a human pathogen — to deliver the human gene to mice with propionic acidemia. All affected mice that did not receive AAV gene therapy died immediately after birth. However, most of the mice with propionic acidemia that received gene therapy survived, some for as long as seven months after a single injection of virus.

"We are the first to rescue mice with this lethal organic acidemia using gene therapy and believe these studies will give the patients and families hope that modern treatments will someday be available for propionic acidemia," Dr. Venditti said.

Last Reviewed: February 25, 2012