A blind man has had his sight partly restored after a form of gene therapy that uses pulses of light to control the activity of nerve cells – the first successful demonstration of so-called optogenetic therapy in humans.
The 58-year-old man, from Brittany in northern France, was said to be “very excited” after regaining the ability to recognise, count, locate and touch different objects with the treated eye while wearing a pair of light-stimulating goggles, having lost his sight after being diagnosed with retinitis pigmentosa almost 40 years ago.
The breakthrough marks an important step towards the more widespread use of optogenetics as a clinical treatment. It involves modifying nerve cells (neurons) so that they fire electrical signals when they’re exposed to certain wavelengths of light, equipping neuroscientists with the power to precisely control neuronal signalling within the brain and elsewhere.
Christopher Petkov, a professor of comparative neuropsychology at Newcastle University medical school, said: “This is a tremendous development to restore vision using an innovative approach. The goal now is to see how well this might work in other patients with retinitis pigmentosa.”
This group of rare, genetic disorders, which involves the loss of light-sensitive cells in the retina, affects more than 2 million people worldwide, and can lead to complete blindness.
The new technique aims to restore visual function at the late stages of the disease, by injecting a harmless virus that has been modified to carry the genetic instructions for making a light-responsive algal protein, into the eye. These instructions are inserted into specific eye cells called retinal ganglion cells, bypassing the damaged retinal cells, and allowing visual information to be transmitted to the brain when the modified cells are exposed to light.
The light is delivered into the patient’s eye using goggles that capture images from the real world and transform them into pulses at the specific wavelength the gene therapy protein responds to in real time, enabling the man to see.
The study, published in Nature Medicine, describes the first patient treated as part of an international study investigating the safety and tolerability of the treatment. Two patients have also had the treatment in London.
It takes time for the eye cells to start producing the protein and for the brain to become accustomed to the new system. Prof José-Alain Sahel at the University of Pittsburgh school of medicine, who co-led the study, said: “Initially, the patient couldn’t see anything with the system, and obviously this must have been quite frustrating. And then spontaneously, he started to be very excited, reporting that he was able to see the white stripes [of a zebra crossing] across the street.”
His vision improved with further training, although it is not completely restored and he still cannot recognise faces. However, the treatment was well tolerated, and the results expected to be long-lasting.
“I think there’s a new scientific field [being] born here, namely visual rehabilitation,” said the study co-leader Prof Botond Roska at the University of Basel in Switzerland. “What these ganglion cells are telling the brain is not the normal activity of the ganglion cells. What we are getting into is [teaching] the brain of a 60-year-old a new language.”
Prof Gero Miesenböck, the director of the Centre for Neural Circuits and Behaviour at the University of Oxford, who co-won the Brain prize in 2013 for the invention and refinement of optogenetics, said: “The study represents a significant milestone in therapeutic applications of optogenetics. There has been much speculation – and also a rather large amount of hype – about such applications since the early days of the technology, which originated 20 years ago as a research tool.”
There are still major obstacles to overcome before optogenetic treatment can be used more widely, including identifying the relevant brain cells to be modified, and finding ways to safely introduce light sources into the brain.
Miesenböck said: “If optogenetic treatments for other neurological and psychiatric indications are to become a reality, we need to advance our fundamental understanding of the relevant brain structures. This, not technological issues, is the most serious obstacle to wider optogenetic applications.”
