GenSight Biologics, a biopharmaceutical company based in France, is developing gene therapies for rare diseases that cause blindness. The company has recently received approval in the UK for its Phase I/II PIONEER trial, which will test a treatment combining gene therapy with a visual stimulation device for people with retinitis pigmentosa, an incurable genetic disease that causes blindness. The treatment is called GS030 and the company expects to treat the first patient in the UK in the first quarter of 2018.
The trial will involve patients receiving three increasing doses of a gene therapy, through injection into the eye, and participants will be monitored to assess the safety of the treatment at each dose level. The gene therapy introduces a light-sensitive protein into cells in the retina. The patients also use optogenetic goggles, which capture light and then transmit it to the patient’s eyes, specifically to stimulate the genetically-modified cells and enhance their vision. If effective, the technology also holds promise for other diseases involving degeneration of photoreceptors in the retina.
Medgadget asked GenSight Biologics CEO Dr. Bernard Gilly some questions about the concept and the trial.
Conn Hastings, Medgadget: Can you give us some background on retinitis pigmentosa and the current lack of treatments?
Bernard Gilly, GenSight Biologics: Retinitis pigmentosa is a group of genetic disorders of the retina that cause loss of vision. Mutations in one of more than 100 genes are involved and the underlying mechanism is linked to a progressive loss of rod photoreceptors in the back of the eye, followed by the loss of cone photoreceptors. Vision loss is progressive, starting around the age of 18 and evolving to legal blindness around the age of 45. There is no cure for retinitis pigmentosa.
Medgadget: Please tell us about optogenetics. Has this technique ever been trialed clinically before?
Bernard Gilly: Optogenetics is a biological technology that involves the use of light to control neurons in living tissues, that have been genetically modified to express a light-sensitive protein, typically ion channels. It is a neuromodulation method that uses a combination of techniques from optics and genetics to control and monitor the activity of individual neurons in living tissues and understand their functioning mechanisms. Although it is widely used in research labs, GenSight is pioneering the use of optogenetics as a therapeutic approach combining a gene therapy with a stimulation device to amplify the signal, expecting to restore sight in blind patients.
Medgadget: Can you talk us through the different components of the GS030 treatment?
Bernard Gilly: There are two main components to the therapeutic approach: one is a drug product (DP), the second is a wearable optronic stimulation device (SD). The DP is a gene therapy product consisting of an AAV vector carrying the gene encoding for the light-sensitive protein (in our product the protein is a modified channelrhodopsin called ChrimsonR). The DP is administered to the patient through a single intravitreal injection. The SD consists of goggles the patient will have to wear. These goggles are capturing visual information via a neuromorphic sensor, and then this visual information is processed by an algorithm before a digital micro-mirror sheds the red-lighted visual information to the retina cells expressing ChrimsonR. This causes them to produce an action potential that is sent to the brain.
Medgadget: Does the gene therapy target the specific mutations that causes retinitis pigmentosa? If not, how does it work?
Bernard Gilly: No, the optogenetic approach can apply to any mutation causing retinitis pigmentosa, provided that the optic nerve is functional. Indeed, the optogenetic approach is transferring the photoreceptor function into other cells in the retina that do not degenerate because of mutations (typically the retinal ganglion cells). It could, in fact, also apply to treat a late form of dry macular degeneration.
Medgadget: Will patients wear the optogenetic goggles at all times, or just for specific treatment periods, to stimulate the transduced cells?
Bernard Gilly: In principle they will be free to wear and use the goggles as they want or as they need. When the goggles are off, the patients will simply be blind as before. The device has been designed so that they could use it as long as they want to (several hours) but we believe that they will not use it permanently.
Medgadget: Please tell us about the upcoming PIONEER trial. What are the primary outcome measurements?
Bernard Gilly: PIONEER is a first-in-man, multi-center, open label dose escalation Phase I/II clinical trial designed to assess the safety and the tolerability of GS030 in end-stage RP patients. As we will follow patients for several months, and because these patients will be blind at T0, we are also going to follow the evolution of their sight and in particular measuring the usefulness of the vision they will be able to form.
Link: GenSight Biologics…