GenSight's Optogenetic Therapy Advancing Toward Human Study
GenSight Biologics, a newly formed gene therapy development company in France, is making significant progress in the advancement of an optogenetic treatment for restoring vision in people who have lost all of their photoreceptors to retinal diseases such as retinitis pigmentosa (RP). The company’s goal is to launch a clinical trial in 2015.
“When we formed the company, we thought about the best approaches for reversing blindness, especially orphan conditions,” says Bernard Gilly, Ph.D., co-founder and executive chairman at GenSight. “And it was important for us to help patients who could suffer from blindness for 20 years or longer.”
The project is building on the advancement of a similar therapy being developed by José-Alain Sahel, M.D., of the Institut de la Vision, and Botond Roska, M.D., Ph.D., of the Friedrich Miescher Institute — an effort funded through the Foundation’s Translational Research Acceleration Program (TRAP). Established in 2008, the goal of TRAP is to expedite the advancement of promising retinal-disease treatments into human studies. Twenty million dollars is targeted annually for TRAP-funded projects.
Optogenetics is an emerging therapeutic approach that involves the delivery of genes to cells of the retina, brain or other neural tissue to make them light-sensitive. In addition to being developed for retinal diseases, optogenetics shows potential for treating Parkinson’s disease, sleep disorders, depression and other neurological conditions. By making neural cells light-sensitive, they can be controlled to minimize or reverse symptoms.
The GenSight optogenetic treatment uses an adeno-associated virus (AAV) for delivery of a gene expressing halorhodopsin, a light-sensitive protein similar to rhodopsin, which is naturally produced in photoreceptors to make vision possible. The treatment is administered to either non-functional photoreceptors or, in cases where photoreceptors have been completely lost, to inner retinal cells, such as bipolar cells, which often survive in advanced diseases.
Dr. Gilly says that a visual interface — a pair of high-tech glasses with a camera — is also being developed by GenSight to enhance the visual experiences of patients receiving the optogenetic gene therapy. In simple terms, the interface provides some of the visual processing functions that photoreceptors would normally provide, and it also delivers light to bipolar cells in a wavelength that activates halorhodopsin.
Researchers have thus far demonstrated that the treatment elicits visual behavior in a mouse model of advanced retinal degeneration as well as light sensitivity in a culture of human retinal cells. “We believe this is a very strong proof of concept,” says Dr. Gilly.
In preparation for a clinical trial, toxicology studies will be performed. GenSight will also produce the treatment using good manufacturing practices to ensure that it meets quality and safety standards for use in humans.
While the therapy will initially be studied in humans with rare, inherited retinal diseases, Dr. Gilly says the company would also like to eventually make it available to people with age-related macular degeneration.
For information on other TRAP-related projects, see this overview.