Excellent therapy brings light into the darkness

Blind people could one day 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 honouring two scientists who have laid the foundations for this with the Translational Neuroscience Prize. Botond Roska from the Institute of Molecular and Clinical Ophthalmology in Basel has genetically modified cells in the retina of the eye so that they take over the function of defective sensory cells. José-Alain Sahel from the Sorbonne University in Paris has developed a gene therapy for those affected 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 on 22 June 2023 in Hamburg.

Hereditary or age-related defects of the retina are often the cause of loss of sight. With over two million people affected worldwide, retinitis pigmentosa is one of the most common hereditary retinal diseases. Various mutations cause the sensory cells of the retina to degenerate. Apart from an approved therapy for the early stages of the disease, it is not yet possible to restore sight to people who are already blind.

A tiny alga has shown researchers new ways to treat this disease.

Chlamydomonas reinhardtii consists of just a single cell and has no eyes. However, thanks to light-sensitive proteins, the algae can still move towards the light. These proteins, known as channelrhodopsin, are similar to the light-sensitive molecules in human sensory cells in the eye. Researchers have introduced the gene for a channelrhodopsin into other cells and thus made them light-sensitive. This technique, known as optogenetics, has led to many new insights in the neurosciences. Its use is also being researched for the treatment of deafness.

Restored vision

Botond Roska has investigated the functions of the various cell types in the retina and the effects of genetic defects in these cells. He developed a method with which he can introduce genes into specific cell types using harmless viruses. In this way, Roska has succeeded in restoring the vision of blind mice and human retinas.

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

For a clinical trial, the researchers treated a patient with retinitis pigmentosa who had gone blind over a decade ago. The team introduced a gene for the light-sensitive molecule Chrimson R into the patient's retina. This made so-called retinal ganglion cells sensitive to light. These nerve cells are naturally unable to receive optical signals. It took almost five months before the cells produced the protein permanently and the patient was able to perceive the first visual impressions.

Chrimson R only reacts to the yellow-orange part of the light spectrum. However, this part of the spectrum is not sufficient to adequately perceive the surroundings under normal lighting conditions. The team led by José-Alain Sahel therefore developed light-amplifying glasses that record the surroundings with a camera, convert the signals into yellow-orange light and transmit them to the patient's retina in real time. Intensive training was required to see with the special glasses. After seven months, the patient was able to localise, touch and count objects in front of his eyes. The scientists have since confirmed these findings in other patients. Measurements of brain activity showed that the visual centre in the brain was activated.

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

The award winners

Botond Roska first studied cello and mathematics in Budapest. He then earned his doctorate in medicine at Semmelweis Medical School, graduated in neurobiology at the University of California, Berkeley, and studied genetics and virology as a Harvard Society Fellow at Harvard University and Harvard Medical School. From 2005 to 2018, he headed a research group at the Friedrich Miescher Institute in Basel. He has been a professor at the Faculty of Medicine since 2010 and a professor at the Faculty of Natural Sciences at the University of Basel since 2019. Since 2018, he has been one of the founding directors of the Institute of Molecular and Clinical Ophthalmology Basel. There, he heads a research group that focuses on understanding vision and its diseases as well as developing gene therapies to restore visual function.

José-Alain Sahel studied medicine in Paris and became an ophthalmologist at the Louis Pasteur University Hospital in Strasbourg in 1984. After various research positions at the Clinic for Eye and Ear Diseases and Harvard University, he became Professor of Ophthalmology at the Louis Pasteur University in Strasbourg in 1988 and at the Sorbonne University in Paris and University College London in 2002. In 2008, he founded the Vision Institute in Paris and headed it until 2021. He has been Professor Emeritus at the Sorbonne University since 2023. Since 2016, he has been an endowed professor and chairman of the Vision Institute at the University of Pittsburgh Medical Centre.

An announcement from the "Max Planck Society" dated 19 June 2023