Award-winning therapy brings light into the darkness

Botond Roska and José-Alain Sahel honored with the International Prize for Translational Neuroscience for developing treatment for hereditary blindness

June 19, 2023

Blind people may one day be able to see again. Research has come a big step closer to this goal, which sounds like a biblical miracle, in recent years. This year, the Gertrud Reemtsma Foundation is awarding the International Prize for Translational Neuroscience to two scientists who have laid the groundwork. Botond Roska of the Institute of Molecular and Clinical Ophthalmology Basel has genetically modified cells in the retina of the eye to take over the function of defective sensory cells. José-Alain Sahel of Sorbonne University in Paris has developed a gene therapy for patients and light-enhancing glasses as a visual prosthesis. A patient who had gone blind decades ago was able to perceive light stimuli from his environment again thanks to the treatment. The Translational Neuroscience Prize will be awarded in Hamburg on June 22, 2023.

Hereditary or age-related defects of the retina are often the cause of eyesight loss. Retinitis pigmentosa is one of the most common hereditary retinal diseases, affecting more than two million people worldwide. Various mutations cause the sensory cells of the retina to degenerate. Except for one approved gene therapy in rare early onset condition, it has not yet been possible to restore sight to people who are already blind.

A tiny green alga has shown research new ways towards a therapy for this disease. Chlamydomonas reinhardtii consists of only one cell and has no eyes. But thanks to light-sensitive proteins, the alga can still move toward the light. These proteins, known as channelrhodopsins, are similar to the light-sensitive molecules in human sensory cells in the eye. Researchers have inserted the genes for the channelrhodopsin into other cells, making them light-sensitive. This technique, known as optogenetics, has provided many new insights in neuroscience. Its use is also being explored for the treatment of deafness.

Restoring vision in mice and humans

Botond Roska has studied the functions of different cell types in the retina and the effects of genetic defects in these cells. He developed a method that allows him to insert genes into the genome of specific cell types using harmless viruses. In this way, Roska has succeeded in restoring vision in blind mice and human retina.

In order to test the technique on humans, José-Alain Sahel developed a gene therapy for humans. Sahel is an ophthalmologist researching new drug therapies, retinal prostheses, and gene therapies to treat hereditary or age-related defects of the retina.

For one clinical trial, researchers treated a patient with retinitis pigmentosa who had gone blind more than a decade ago. The team inserted a gene for the light-sensitive molecule Chrimson R into the patient's retina. This made retinal ganglion cells, which naturally cannot receive optical signals, light-sensitive. It took nearly five months for the cells to produce the protein permanently and for the patients to start interpreting the signals.

Chrimson R reacts only to a small part of the spectrum of the visible light, namely yellow-orange light. However, this is not sufficient to adequately perceive the environment under normal lighting conditions. The team led by José-Alain Sahel therefore developed light-enhancing glasses that record the surroundings with a camera, convert the signals into the respective wavelengths and transfer them to the patient's retina in real time. Intensive training was required for the patient to see with the special glasses. After seven months, he could locate, touch and count objects in front of his eyes. These findings have been now observed in other patients in this trial. Measurements of brain activity showed that the visual center in the brain was activated in the process.

The results show that optogenetic therapy can at least partially restore vision in people with retinitis pigmentosa. However, before the treatment can be used in clinics, it must first be tested and optimized in further studies.

The award winners

Botond Roska first studied cello and mathematics in Budapest. He then obtained his M.D. at the Semmelweis Medical School, a Ph.D. in neurobiology from the University of California, Berkeley and studied genetics and virology as a Harvard Society Fellow at Harvard University and the Harvard Medical School. He then led a research group at the Friedrich Miescher Institute in Basel from 2005-2018. In 2010 he became Professor at the Medical Faculty and in 2019 Professor at the Science Faculty of the University of Basel. Since 2018 he is a founding director of the Institute of Molecular and Clinical Ophthalmology Basel. There, he leads a research group focusing on the understanding of vision and its diseases and the development of gene therapies to restore vision.

José-Alain Sahel studied medicine in Paris  and became an ophthalmologist at Louis Pasteur University Hospital in Strasbourg in 1984. After a fellowship at the Massachusetts Eye and Ear Infirmary, Harvard Medical School, and a visiting scholarship at Harvard University, he became a Professor of Ophthalmology at Louis Pasteur University in Strasbourg in 1988, and in 2002 at Sorbonne University in Paris, and University College London. He founded the Vision Institute in Paris in 2008 and directed it until 2021. Since 2023 he is professor emeritus at Sorbonne University. Since 2016 he is endowed Distinguished Professor and Chairman of the Vision Institute at the University of Pittsburgh Medical Center.

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