Restoring Vision Seeking the Elixir

Author:  Maria Huang

Institution:  Duke University
Date:  May 2008

Recently, two teams from the University of Pennsylvania and University College London applied gene therapy to treat a degenerative eye disease. Published in the New England Journal of Medicine, the research article investigates a form of LCA2 (Leber's congenital amaurosis). Currently untreatable, LCA is a group of inherited blindness disorders that affects about 3000 Americans, and its onset occurs at birth. Affected individuals gradually begin to lose light-sensing photoreceptors in the retina until they become completely blind at age 40.

The research teams focused on the RPE65 gene (retinal pigment epithelium 65), which contributes to the development of a cell layer near the back of the eye. RPE65 also codes for an enzyme that converts vitamin A into a form used to produce rhodopsin, the optical pigment that absorbs light. Lacking rhodopsin, photoreceptor cells eventually die.

The researchers reasoned that injecting the RPE65 gene into patients afflicted with LCA2 would restore photoreceptor function. In 2001, some gene therapists reported in Nature Medicinethat a treatment with RPE65 restored vision in young dogs.

Subsequently, Penn researchers Jean Bennett and Albert Maguire launched an LCA2 trial in adults. Later joined by Robin Ali's team at University College London, the research group decided not to treat children first because this occasion marked the first time that a gene therapy vector had been injected into human retina. Moreover, adults have more viable retinal tissue. Ali added, "If it had been a catastrophe, we would have been open to the criticism that we rushed into this with an 8-year-old."

While the UK team began its first trial in February 2007, the CHOP team started later in October with a 19-year-old and two 26-year-olds. The injection surgery involved delivering a recombinant virus, which is a virus that carries a modified piece of DNA coding for a specific trait. Investigators introduced the virus to the tissue under the retina. Although the initial injection caused a small macular hole in one of the patients, no negative immune complications arose.

After a few weeks of observing pupil constrictions, the research teams discovered that the treated patients could detect three times more light than before. In addition, two patients who could only discern hand movements previously now were able to read several lines of eye chart. One of the 26-year-olds even regained the capability of navigating through an obstacle course. Bennett voices his surprise, "I couldn't believe it."

The team at University College London also found that one of their 18-year-old patients demonstrated improved light perception because he no longer stumbled through a dimly lit, simulated night street scene.

These developments have garnered approval from gene therapy researchers, including Arthur Nienhuis of St. Jude Children's Research Hospital, president of American Society for Gene Therapy. Now that the have established the first round of safe trials in adults, Bennett and Maguire plan on treating younger patients. Bennett says that gene therapy for eye disease "opens up so many opportunities."

Written by Maria Huang

Reviewed by Nadia Ramlagan, Pooja Ghatalia

Published by Pooja Ghatalia