Gene Therapy for LCA Caused by RD3 Mutations Performs Well in Lab Study

July 10, 2013

A research team led by Robert Molday, Ph.D., at the University of British Columbia in Vancouver, has moved a step closer to developing a gene therapy for people with Leber congenital amaurosis (LCA) caused by mutations in the gene RD3. The investigators used an RD3 replacement gene therapy to restore photoreceptor function in mice with the condition, and plan to test the treatment in canines with RD3 mutations. Results of their mouse study were published in the journal Human Molecular Genetics.

The researchers noted that photoreceptors of the treated mice survived for seven months, which is considered a relatively long time for these animals. They expect that a human version of a similar treatment would last at least several years, if not a lifetime.

The gene therapy, delivered by an injection underneath the retina, consisted of a human-engineered virus — known as adeno-associated virus, or AAV — which contained normal copies of the RD3 gene. The AAV was designed to penetrate photoreceptors to deliver its therapeutic cargo. William Hauswirth, Ph.D., a Foundation-funded researcher at the University of Florida, and the recent recipient of the Llura Liggett Gund lifetime achievement award, provided the AAV delivery system for the study.

RD3 is important to vision, because it leads to the production of a protein that affects the movement of two other proteins (GC1 and GC2) critical to the conversion of light to electrical signals, which ultimately become the images we see. If RD3 is defective and not expressing any protein, GC1 and GC2 become stuck in photoreceptors and are unable to play their role in converting light to vision.

LCA is a severe form of retinitis pigmentosa causing significant vision loss or blindness in early childhood. Researchers have identified 18 genes linked to the autosomal recessive form of LCA, which affects approximately 3,800 people in the United States and thousands more around the world.