Treatment for Leber Congenital Amaurosis

U.S. researchers have taken the first steps in treating an eye disease that causes irreversible blindness in humans by successfully testing two novel treatments in mice.

Leber congenital amaurosis (LCA) is characterized by severe loss of vision at birth, but its causes are not fully understood. Researchers believe that the disease might be due to abnormal development of photoreceptor cells in the retina, extremely premature degeneration of these cells, or when the cells lack essential metabolic ingredients necessary for vision. In a subset of these diseases, it is known that the retina stops functioning due to loss of the lecithin retinol acyl-transferase enzyme (LRAT). LRAT is required for regeneration of a pigment necessary for the eye to detect light.

LCA can be caused by mutations in the gene encoding RPE65, a key protein involved in the production and recycling of 11-cis-retinal in the eye. Currently, there is no treatment for LCA, although previous studies in mice have successfully tested the injection of a virus carrying the normal gene for RPE65, and, separately, oral administration of a vitamin A-like compound.

In this month's open access journal PLoS Medicine, a team led by Krzysztof Palczewski from Case Western University examined the effect of combining the two treatments in blind mice that didn't have the LRAT enzyme. They found that these treatments "provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness."

They noted that the oral treatment was easier to administer compared with injecting the gene therapy directly into the eye, but a disadvantage of the oral treatment was a potential for long-term systemic toxicity compared with the gene therapy. However, toxicological data gathered in this and previous studies have suggested no long term ill effects in mice.

It is possible that each treatment might eventually prove to be more suitable for a specific age group of patients, and therefore, combining the therapies might offer more effective treatment for a wider age range of patients, suggest the authors.

The team hopes that if the treatments are used together, treatment with oral retinoids could begin in infancy to avoid early sight loss and the difficulties associated with surgery in very young patients. And when patients are older, long-lasting drug-free treatment could be done by surgically introducing gene therapy. This study marks the first step in finding out whether these treatments will work effectively and safely in humans.