French firm GenSight Biologics has published pioneering results showing the partial recovery of the first recipient that received their optogenetic therapy.
Retinitis pigmentosa is a progressive, inherited, monogenic (or rarely digenic) disease that causes blindness. It is caused by mutations in over 71 different genes. In addition, it affects more than 2 million people worldwide. However, with the exception of a gene replacement therapy for one form of early-onset retinitis pigmentosa, there are no available therapies.
Optogenetics is a biological technique that involves the use of light to control neurons that have been genetically modified to express ion channels that are sensitive to light. As a result, optogenetics has become a widely used tool in the lab due to its precision. However, its medical potential for treating brain disorders is hindered because getting light inside the head requires implantation of a fibre optic cable. Several groups have been exploring optogenetics for the treatment of blindness. This is because nerve cells in the eyes are exposed to outside light. Optogenetic vision restoration is a mutation-independent approach for restoring visual function.
GenSight’s optogenetic therapy
In this paper, published in Nature Medicine, researchers reported on findings from a phase 1/2a clinical trial for an investigational optogenetic therapy for patients with advanced nonsyndromic retinitis pigementosa.
The therapy combines injection of an optogenetic vector with wearing a medical device (light-stimulating goggles). The optogenetic vector specifically is an adeno-associated viral vector encoding the light-sensing channel rhodopsin protein ChrimsonR fused to the red fluorescent protein tdTomato. This vector was administered by injection into the worse-seeing eye of patients. The goggles are able to detect local changes in light intensity. They then project these light pulses onto the retina in real time to activate optogenetically transduced retinal ganglion cells.
The first individual to get this therapy was a 58-year-old man from Brittany in France. The individual had to perceive, locate, count and touch different objects using the vector-treated eye alone while wearing the goggles. The man found that after a year, he could see the black and white stripes of pedestrian crossings. While he could not see colours or fine details, the case study described partial restoration of his vision.
This is the first reported case of partial functional recovery in a neurodegenerative disease following optogenetic therapy.
Lead and co-corresponding author, Dr. José-Alain Sahel, stated:
“Watching a patient benefit for the first time from this trial using optogenetics to treat blindness has been a uniquely rewarding experience.”
Image credit: By rawpixel – freepik