Olivier Goureau, a research director at the Vision Institute1 , has received the 2019 Research Award – for Health, with Christelle Montville, researcher at the I-Stem2 laboratory. This award recognizes the work of researchers who have succeeded in improving the quality of vision in rats that have retinitis pigmentosa3 , by transplanting a cell patch obtained from human embryonic stem cells.
This unprecedented breakthrough paves the way for cell therapy for the treatment of genetic retinitis pigmentosa, as well as more frequent degenerative retinal diseases, such as some forms of age-related macular degeneration (AMD), which affect more than one and a half million people in France.
Cells essential for sight
A key organ of sight, the retina contains the photoreceptor cells (cones and rods) that capture the light and then transform it into an electrical signal. This information is then transmitted to the ganglion cells and sent by the optic nerve to the brain to be decoded.
The correct functioning of these photoreceptors, at the origin of sight, is ensured in particular by the cells of the retinal pigment epithelium (RPE). These EPR cells, which face the photoreceptors, have a fundamental role. They absorb the excess light rays, to provide the necessary nutrients to the photoreceptors and eliminate, by a mechanism called phagocytosis, the debris they produce.
"In many retinal pathologies, including some retinitis pigmentosa, these cells of the EPR do not function correctly, resulting in the death of photoreceptors and blindness," says Olivier Goureau.
A "patch" of stem cells grafted under the retina
To cure these currently incurable diseases, several research teams, particularly in the United States, have had the idea to rely on advances in stem cells to manufacture and then transplant new EPR cells. In most of these studies, the researchers inject these new cells into a liquid suspension (the cells are separated from each other). But the survival of these cells in suspension is limited and their integration under the retina is not optimal.
To overcome this problem, researchers at the Vision Institute and I-Stem have chosen to transplant epithelial tissue already organized and functional, so it is able to provide, in vitro, the necessary nutrients to the photoreceptors and eliminate the debris they produce.
In this perspective, the researchers used pluripotent human embryonic stem cells that have the particularity to proliferate indefinitely while maintaining their ability to differentiate into all types of cells. Using cell culture techniques, scientists differentiated these stem cells into EPR cells that they allowed to mature for several weeks.
"The originality of our work was to sow these new EPR cells onto a human amniotic membrane, already used in cell therapy, so that they form a functional epithelium. We have implemented a clinical grade procedure, that is to say immediately adaptable to cell therapy in humans, "says the researcher.
Maintained in a layer of gelatin, this cell patch was finally injected and transplanted under the retina of rats with retinitis pigmentosa.
Clinical trial paves the way for cell therapy of retinal pathologies
Much better than those observed with the treatment of cells in suspension, the results obtained by researchers from the Vision Institute and I-Stem are a real hope for people with retinitis pigmentosa affecting the EPR.
"After 10 to 12 weeks of transplantation, we observed that the rats had better visual performances as well as an increased preservation of the number of photoreceptors in the graft area," says Olivier Goureau.
After having validated the safety of the surgical procedure in animals with eyes anatomically close to the human eye, the team was authorized to start a clinical trial in a dozen patients at the hospital in Quinze-Vingts. As a first step, they will have to demonstrate the safety of the treatment before proving its efficacy in humans.
"We hope to be able to treat the first patients with retinitis pigmentosa due to ERP dysfunction during the year 2019," the researcher concludes.
This is the first cell therapy trial for eye diseases in France.
1 Jointly managed by Sorbonne University, Inserm, CNRS
2 Jointly managed by AFMTéléthon, Inserm, University of Évry
3 Retinitis pigmentosa is a rare disease that results in the degeneration of certain retinal cells, such as photoreceptors or retinal epithelial cells. Eventually, their destruction leads to blindness. Currently incurable, this disease is most often due to mutations in certain genes essential for the proper functioning of these cells.