Gene therapy still years away

Editor's Note: Research into the genetics of ocular disease is paying off with discoveries of new genes associated with both common and rare eye conditions. Gene therapy, however, could be 5 to 10 years away for many eye diseases. In this first of a two-part series, researchers explain the progress in age-related macular degeneration (AMD), Leber's congenital amaurosis, and familial exudative vitreoretinopathy (FEVR). In the second half of the series, gains in glaucoma, myopia, and retinitis pigmentosa will be covered as well as a promising therapy for AMD-RNA interference.

Twenty years ago, many scientists held a rudimentary, perhaps simplistic view of gene therapy: if they could find a gene, they could cure the disease.

"That's easy to say, but there's a few steps in the middle," said Howard R. Petty, PhD, whose research at the University of Michigan Kellogg Eye Center, Ann Arbor, includes work on the genetics of ocular disease.

The quick fixes to both rare and common eye diseases that some might have hoped for have not occurred, but years of research in the lab and experiments with animal models are finally starting to pay off, he said.

"We haven't done much yet in patient care," Dr. Petty said. "The more likely scenario is that we're going to understand the genetics, and that's going to give us the mechanism. When we have the mechanism, we can develop small molecules and compounds to treat the eye. I don't think we can cure eye disease, but we are going to be able to develop drugs to manage eye disease very well."

Another researcher agrees that there is a tremendous amount of work to be done in this area.

"It's not only identifying the genes that play a role in disease but it is using that information to help better define and clarify understanding of the diseases and maybe even begin to use the information to identify diseases even earlier," said Eric Postel, MD, associate professor, Duke University Eye Center, Durham, NC.

Gene therapy is an appropriate approach to diseases caused by a recessive gene, in which an individual inherits one damaged copy of a gene from each parent and therefore lacks a normal gene.

"In that case, if the gene is replaced, that's the cure," said Rando Allikmets, PhD, Acquavella associate professor of ophthalmology (in ophthalmology and pathology) and director of the Molecular Genetics Laboratory, Edward S. Harkness Eye Institute, Columbia University, New York.

Dr. Allikmets added that in some cases, it is only necessary to replace a portion of the gene. In a disease caused by a dominant gene, the individual has only a copy of a mutated gene, which has a changed function.

In these cases, the bad copy of the gene must be eliminated to allow a normal one to work properly, Dr. Allikmets said.

When gene therapy is applied in ophthalmology, it will be simpler, for the near future, to treat recessive diseases, Dr. Allikmets said.

"I think we're making good progress in treating some of those rare, retinal diseases," Dr. Allikmets said.

The eye is a particularly good organ for gene therapy, he added, because it is readily accessible and treatment can be targeted to a specific site within the eye or to only one eye, limiting the risk of systemic side effects.

"The future of treatment is specific or tailor-made medicine for each patient with a specific underlying genetic defect," said Kang Zhang, MD, PhD, who specializes in research of retinal diseases.

Today, for the most part, diseases are treated without any understanding or differentiation of the underlying etiology between patients, he added.