French Researchers Planning Clinical Study of Vision-Preserving Protein
A promising treatment aimed at preserving cones, the retinal cells that provide central and daytime vision, is poised to move into a Phase I clinical trial within the next year. Known as rod-derived cone viability factor (RdCVF), the therapeutic protein has consistently preserved vision in several preclinical studies.
RdCVF has received an orphan medicinal product designation from the European Commission, a regulatory agency similar to the FDA in the U.S. The orphan designation provides marketing, financial, and clinical research benefits to Fovea Pharmaceuticals, the French company developing the treatment.
In 2005, Drs. José-Alain Sahel and Thierry Léveillard received the Foundation’s Annual Trustee Award for their discovery of RdCVF as a potential vision-saving treatment. The Foundation-funded French research team screened 210,000 genes to find a rod-derived protein that would protect cones.
A majority of retinal degenerative diseases, including retinitis pigmentosa (RP), are caused by mutations in genes that affect rod cells. As a result, rods are the first photoreceptors to degenerate. Rods provide peripheral eyesight and vision in dark settings.
However, once rods are gone, cones subsequently degenerate. This phenomenon led researchers to suspect that rods were secreting a factor (or multiple factors) that helped to preserve cones.
Initially, the France-based clinical trial will involve monthly ocular injections of RdCVF into people with RP. The investigators are also evaluating gene therapy as a delivery mechanism to provide long-term, sustained release of RdCVF. One gene therapy treatment will likely be effective for several years.
While the researchers will initially evaluate RdCVF in people with RP, they believe the treatment may preserve vision in people with a wide range of retinal degenerative diseases.
Dr. Sahel notes that by keeping as few as 5 percent of cones alive, a person can continue to function independently.
Drs. Sahel and Léveillard are co-founders of Fovea Pharmaceuticals. Dr. Sahel is center director for the Foundation’s Paris Research Center for the Study of Retinal Degenerative Diseases.作者: 雪山飞狐 时间: 2010-8-5 09:03
An international research team, funded in part by the Foundation Fighting Blindness, has used gene therapy to reactivate retinal cells that were previously unresponsive to light. The treatment was delivered to cones, the retinal cells that provide central and daytime vision. Investigators evaluated the gene therapy in two mouse models of retinal degenerative disease, as well as cultures of human retinal tissue. Using a variety of tests, the researchers demonstrated that the treated cells restored functional vision, and that the restoration of vision persisted over a long period of time.
In retinal degenerative diseases such as retinitis pigmentosa, cones stop providing vision before they die and can remain in a compromised state for several years. The gene therapy used to restore vision in the cone-reactivation study leads to the production of a light-sensitive protein called halorhodopsin, which is similar to vision-activating proteins occurring naturally in the retina. The presence of halorhodopsin appears to reactivate the visual cycle, the biochemical process in retinal cells that lead to vision.
An adeno-associated virus (AAV), a therapeutic virus, was used to deliver the treatment to the cones. AAVs are the same delivery mechanism used in landmark gene therapy clinical trials that have restored vision in 28 children and young adults who were virtually blind from Leber congenital amaurosis.
Dr. José-Alain Sahel, one of the cone-reactivation study investigators and director of the Foundation-funded Paris Research Center for the Study of Retina Degenerative Diseases, says that through high-resolution imaging, his team has identified people who may be good candidates for a future clinical trial. He adds that even people who are legally blind might have some cones reactivated and vision restored.
Dr. Sahel also notes that the cone-reactivation treatment has the potential to be even more beneficial if coupled with a therapy that helps protect cones from degeneration. Dr. Sahel and his team are planning a clinical trial of a neuroprotective treatment called rod-derived cone viability factor, or RdCVF, which has shown excellent results for preserving cones in preclinical studies.
The cone-reactivation study was led by Dr. Botond Roska of the Friedrich Miescher Institute for Biomedical Research in Switzerland, and included scientists from several European research institutions. Results of the study were published in the June 24 issue of the journal Science作者: 雪山飞狐 时间: 2010-8-5 20:18
