Progress Reported in Gene Therapy Development for Best Disease

May 23, 2013

A Foundation-funded research team led by investigators from the University of Pennsylvania has reported that its emerging gene therapy for Best disease, a form of inherited macular degeneration, has cleared all the vision-robbing lesions in canines with the condition. Success in the study moves scientists closer to a human study of the treatment. Dr. Karina Guziewicz in collaboration with Dr. Gus Aguirre’s lab at the University of Pennsylvania, reported study results on May 9, during the annual meeting of the Association for Research in Vision and Ophthalmology.

In the study, 13 canines with Best disease had one eye treated with the gene therapy. The treatment consisted of healthy copies of the Best1 gene, which were contained in a human-engineered adeno-associated virus, or AAV. The AAV was designed to deliver copies of the therapeutic gene to retinal cells, and is administered through an injection underneath the retina.

Dr. Guziewicz said that additional research — including dosing and toxicity studies — is required to ready the treatment for study in humans. The scientists are also investigating optimal regions of the retina for injection of the therapy. They believe a single treatment will last several years in humans.

“Canine studies conducted by Dr. Gus Aguirre’s team have been pivotal to the advancement of a number of gene therapies, including those for Leber congenital amaurosis, achromatopsia and X-linked retinitis pigmentosa,” says Dr. Stephen Rose, chief research officer, Foundation Fighting Blindness. “These studies are a critical stepping stone to human clinical trials.”

The age of onset and severity of Best disease, also known as vitelliform macular dystrophy, vary widely. The condition is characterized by a build-up of lipofuscin — toxic waste products — which accumulate in a layer of cells known as the retinal pigment epithelium (RPE). The RPE plays a supportive role for photoreceptors, the cells that make vision possible. When it degenerates from waste build-up, photoreceptors, and vision, are lost. A fluid-filled sack can also develop, and rupture, underneath the retina.

Best disease is usually dominantly inherited, meaning it is passed along by one parent affected by the condition. However, there are cases of recessive inheritance in which both parents are unaffected carriers. Dr. Guziewicz believes her team’s emerging gene therapy can be adapted to work for both forms of Best disease.

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