Gene therapy for ocular pathologies approaches clinical phase

PARIS — Gene therapy is becoming a realistic treatment option for a number of ocular pathologies, including tumors, glaucoma, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and various congenital forms of retinal and optic nerve degenerations.

"In 2009, we will start the clinical trials in France," said Michel Weber, MD, at the meeting of the French Society of Ophthalmology.

So far, encouraging results have been achieved in in vitro and in vivo animal studies.

"We found a natural model in dogs with a mutation of the RPE 65 gene, which both in animals and humans is a genetic risk factor for Leber"s disease. Gene replacement by injection of adeno-associated virus (AAV) vectors led to restoration of the retinal function and to consequent visual recovery," Fabienne Rolling, MD, said.

After gene replacement in one eye, the ability of the dogs to zigzag in between obstacles was tested.

"When we patched the untreated eye, the dogs were able to find their way without problems. When we patched the treated eye, they had enormous difficulties," Dr. Rolling said.

The best way of delivering the therapy is being evaluated, as ocular coherence tomography showed the injection causes localized trauma.

"It"s mandatory that subretinal injection of the therapeutic vector should be performed outside the fovea," Dr. Rolling said.

AAV-mediated gene transfer has also proved effective in the treatment of albinism, according to a study carried out at the Telethon Institute of Genetics and Medicine in Naples.

"Animal testing has demonstrated that gene therapy can trigger the production of melanin, ameliorating retinal function," said Enrico Maria Surace, MD.

Encouraging results were also achieved in the treatment of anterior uveitis by gene transfer with non-viral vectors in a study carried out in Paris and presented by Yvonne De Kozak, MD.