Man’s eyesight partially restored with optogenetic therapy
pharmafile | May 25, 2021 | News story | Manufacturing and Production |
A man in France has had his eyesight restored after 20 years of complete blindness, in the first reported case of partial functional recovery in a neurodegenerative disease after optogenetic therapy.
The 58-year-old man took part in the Phase I/2a PIONEER study where he received a combined treatment of an intraocular injection of an adeno-associated viral vector, encoding ChrimsonR with light stimulation via engineered goggles. The goggles detect local changes in light intensity and project corresponding light pulses onto the retina in real time to activate optogenetically transduced retinal ganglion cells.
The optogenetic vector used in the study is derived from algae proteins, light-sensing channelrhodopsin protein, ChrimsonR, fused to the red fluorescent protein, tdTomato. This vector was administered by a single intravitreal injection into the worse-seeing eye to target mainly foveal retinal ganglion cells.
The proteins used sense amber light, which is safer for retinal cells than the blue light used for other types of optogenetic research, and the goggles developed were outfitted with a camera that captures and projects visual images onto the retina at amber light wavelengths.
The study found that after treatment the patient perceived, located, counted, and touched different objects using the vector-treated eye alone while wearing the goggles. During visual perception, multichannel electroencephalographic recordings revealed object-related activity above the visual cortex.
The patient involved in the study had been diagnosed with retinitis pigmentosa (RP), a progressive, inherited, monogenic or rarely digenic blinding disease, caused by mutations in more than 71 different genes. It affects over two million people worldwide, and with the exception of a gene replacement therapy for one form of early-onset RP caused by mutation in the gene RPE65, there is no approved therapy.
José-Alain Sahel, first and corresponding author of the study and Founding Director of the Institut de la Vision, said: “Enabling a patient to regain partial vision by optogenetics could not have happened without the engagement of the patient, the efforts of our multidisciplinary team at the Institut de la Vision and GenSight, and the longstanding collaboration with Botond Roska, which was at the origin and core of all this project.”
Botond Roska, last and corresponding author, Founding Director at IOB and Professor at the University of Basel, said: “The findings provide proof-of-concept that using optogenetic therapy to partially restore vision is possible.”
Training with the goggles began nearly five months after the injection, giving ChrimsonR expression time to stabilise in ganglion cells. Seven months later, the patient began reporting signs of visual improvement. The test results showed the patient could locate, touch and count objects on a white table placed in front of him, but only with the aid of the goggles.
One test involved perceiving, locating, and then touching a large notebook or a smaller staple box. The patient touched the notebook during 36 of 39 separate evaluations (92% of the time), but could pick out the smaller staple box only 36% of the time. In a second test, the subject correctly counted glass tumblers on the table 63% of the time.
During a third test, the subject wore a skull-cap affixed with electrodes that took non-invasive electroencephalography (EEG) readings of his brain activity. A tumbler was alternately taken on or off the table, and the subject had to press a button indicating whether it was present or absent. Importantly, EEG readings showed that correlated changes in activity during this testing were concentrated in the visual cortex.
The team also trained a software decoder to evaluate the EEG readings. By simply measuring neuronal activity, the decoder could tell with 78% accuracy if the tumbler was present or not in a given trial. This last evaluation, Roska says, helped to confirm that brain activity is indeed related to a visual object, and “therefore that the retina is no longer blind.”
Sahel said: “Importantly, blind patients with different kinds of neurodegenerative photoreceptor disease and a functional optic nerve will potentially be eligible for the treatment. However, it will take time until this therapy can be offered to patients.”
Kat Jenkins
