ARVO Research Highlights from Foundation's Scientific Advisory Board

June 13, 2014

Held annually in May, the meeting of the Association for Research in Vision and Ophthalmology (ARVO) is one of the world’s largest gatherings of eye researchers. Leading retinal scientists and clinical investigators, including several members of the Foundation’s Scientific Advisory Board (SAB), attended this year’s event to present and discuss the latest research advancements for understanding retinal degenerative diseases and developing sight-saving treatments and cures.

After the meeting, the Foundation polled its SAB to see which projects piqued members’ interests most. Here is a review of some of their selected highlights:

Breakthroughs in Surgical Technique for Choroideremia Gene Therapy
Last January, Robert MacLaren, M.D., reported impressive vision improvements for the choroideremia gene therapy clinical trial underway at the University of Oxford in the United Kingdom. ARVO provided him the opportunity to discuss his innovative surgical technique, which uses a foot pump to carefully administer the therapy underneath fragile, degenerating retinas. He delivered the therapy, contained in a small drop of liquid, just below the macula, the central area of the retina most critical for vision, without causing any permanent detachment or damage. Retinal surgeons involved in current and forthcoming gene therapy clinical trials will benefit greatly from what he has learned and demonstrated.

Gene Therapy Performs Well in Early and Late Stage XLRP Model
Previous research performed by Gus Aguirre, V.M.D., Ph.D., and William Beltran, V.M.D., Ph.D., at the University of Pennsylvania, showed that gene therapy prevented vision loss in early-stage X-linked retinitis pigmentosa (XLRP) canine models. New studies demonstrated that the treatment halted degeneration, preserving retinal function, in mid- and late-stage disease as well. These results provide hope that a future gene therapy will benefit the majority of people with XLRP. Drs. Aguirre and Beltran are funded by the Foundation for their XLRP gene therapy research. Applied Genetic Technologies Corporation is planning to launch a clinical trial of an XLRP gene therapy.  

Promising Approach Emerges for Treating Dominant RP
Autosomal dominant retinal diseases, including autosomal dominant retinitis pigmentosa (adRP), are caused by a defect in one of two copies of a specific gene. That is, one copy is normal, and the other is expressing a toxic protein. Researchers from the University of California, San Francisco, are developing a treatment called an antisense oligonucleotide, which is a small strand of DNA that shuts down the communications of the bad copy, so it can’t express the harmful protein. Researchers believe that the normal copy of RHO will produce enough good protein to provide normal vision. The therapy is being developed for people with adRP caused by P23H mutations in RHO. In mouse studies, the therapy slowed loss of photoreceptors and improved retinal sensitivity.

Adaptive Optics as a Future Clinical Trial Endpoint
Developed to minimize atmospheric distortion when using telescopes to study the cosmos, adaptive optics is becoming a powerful technique for obtaining detailed images, including video, of the human retina down to the level of individual photoreceptors and their inner and outer segments. In a study of people with Stargardt disease, Michel Michaelides, M.D., a Foundation-funded scientist at the University College London, was able to identify the progressive loss of photoreceptors at three-month intervals in a 7-year-old patient — an accomplishment that would not have been possible using traditional imaging equipment. His goal is to develop adaptive optics so that it can be used to quickly and precisely measure treatment efficacy in human studies of potential therapies. 

More Than 40 Induced Pluripotent Stem Cell Projects Presented
It was only seven years ago that researchers first discovered they could reprogram a sample of skin or blood to become stem cells — stem cells that could be coaxed to become virtually any cell type in the body, including retina. Known as induced pluripotent stem cells, or iPSC, they can be used to develop human models of disease, as a treatment-testing platform and as therapies for replacing lost photoreceptors and other cells in the retina. This year, investigators presented results from more than 40 iPSC projects, including those for choroideremia, retinitis pigmentosa (MAK gene), age-related macular degeneration and Batten disease, a fatal pediatric condition that also causes blindness.

For more 2014 ARVO highlights, check out the following posts from the Foundation’s Eye on the Cure blog:

LCA Gene Therapy Recipient Featured During Keynote
Breaking the 50-Percent Barrier in Successful Genetic Screenings
Three Promising CEP290 Gene Therapy Alternatives
European Collaboration Developing Cross-Cutting, Vision-Saving Therapies