A blind patient with advanced Retinitis Pigmentosa has had his vision partially restored after treatment with optogenetic therapy. His sensitivity to light has improved and he is now able to locate and touch objects.
An international research team led by Professors José-Alain Sahel and Botond Roska and involving the Institut de la Vision, Quinze-Vingts Eye Hospital, the University of Pittsburgh, the Institute of Molecular and Clinical Ophthalmology in Basel, and the companies Streetlab and GenSight Biologics, has demonstrated that optogenetic therapy can partially restore vision in a blind patient with advanced retinitis pigmentosa. The results of the study, a world premiere, were published in the journal Nature Medicine on May 24, 2021.
Optogenetic therapy involves genetically modifying cells to produce light-sensitive proteins called channelrhodopsins. The latest clinical trial showed that the technique can partially restore vision in a blind patient. This result marks an important step in the development of mutation-independent gene therapies to treat inherited retinal degenerations.
Although optogenetics, a technique that has been around for about 20 years, has revolutionized basic neuroscience research to study how neural circuits work, this is the first time that this innovative approach has been applied to humans and its clinical utility has been demonstrated.
Treatment of inherited photoreceptor diseases
“Allowing a person to regain some vision through optogenetics would not have been possible without the commitment of the patient, the efforts of our multidisciplinary team at the Vision Institute and GenSight, and the long-standing collaboration with Botond Roska, explains José-Alain Sahel, Professor at the Sorbonne University, Head of Department at Quinze-Vingts Hospital, Founder of the Vision Institute, and Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh.
The goal of this research is to treat inherited photoreceptor diseases, which are a common cause of blindness. Photoreceptors are light-sensitive cells in the retina that use proteins called opsins to transmit visual information to the brain via the optic nerve.
Introduction of the ChrimsonR gene
Photoreceptors progressively degenerate, leading to blindness. To restore light sensitivity, the research team used gene therapy methods to express channelrhodopsins in retinal ganglion cells. For this study, they introduced the coding gene for a channelrhodopsin called ChrimsonR. This opsin detects amber light, which is safer for retinal cells than blue light used in other types of optogenetic research. The researchers have also developed special goggles equipped with a camera. These produce visual images that are projected onto the retina as amber images.
Perceiving light, locating and touching objects
The patient in this clinical trial was diagnosed with retinitis pigmentosa at such an advanced stage that he could only perceive light. Five months after he was injected with ChrimsonR, testing with the goggles began. Seven months later, the patient began to report signs of improved vision. Test results showed that he can now locate, count, and feel objects with the help of the goggles.
“Blind people with different types of photoreceptor neurodegenerative diseases and a functional optic nerve are potentially eligible for this treatment, but it will take some time before this therapy can be offered. GenSight Biologics intends to initiate a Phase 3 trial in the near future to confirm the efficacy of this therapeutic approach,” Prof. Jose-Alain Sahel concludes.
How was the patient tested?
The first test consisted of perceiving, locating, and touching a large notebook or a small box of staples. The patient touched the notebook in 36 of 39 individual tests ( 92% of the time), but could only grasp the staple box in 36% of the tests. A second test involved counting cups on a table. The patient was successful 63% of the time.
Finally, the third test involved measuring the patient’s brain activity with an electroencephalography (EEG) headset. A cup was alternately placed on or removed from the table; the subject had to press a button indicating whether it was present or absent. EEG measurements showed that the correlated activity changes during these tests were concentrated in the visual cortex.
At the same time, a decoding program was installed to interpret the EEG recordings. By analyzing the neural activity, the program was able to tell with 78% accuracy whether or not the cup was present in a trial. This last evaluation, Prof. Roska points out, confirmed that brain activity is indeed related to the presence of an object, and therefore the retina is no longer blind.