Prize Foundation John W. Mouton KBS

Introduction
Every two years, the Fund John W. Mouton Pro Retina (managed by the King Baudouin Foundation) awards a grant of € 30.000 to a researcher working at a university or research center in Europe that is pursuing medical scientific research in the field of the pathologies of the retina. The fund is interested in all kind of retinal diseases (genetic, diabetic, hypertensive, post-prematurity, degenerative, toxic retinopathy, etc.) with exception of retinal tumors. The work may concern clinical research as well as basic research including a concrete perspective on further clinical work. In 2019, the John W. Mouton Pro Retina grant was awarded to prof. Elfride De Baere for her research project Precision medicine in inherited blindness using integrated omics in patient-derived stem cell models.

Scientific abstract
Inherited retinal disease (IRD) is a major cause of early-onset blindness affecting 2 million people worldwide. Significant advances have been made in the genomic underpinnings of IRD, which has culminated in novel therapies entering the clinic. Despite this progress, there are important knowledge gaps that hamper a molecular diagnosis in over half of the cases.
We and others have shown a role for non-coding variation in undiagnosed IRD and demonstrated these are novel targets for therapy. Here, it is our main goal to accelerate diagnosis in unsolved IRD and to uncover novel targets for intervention. First, we will generate human cellular models of undiagnosed monoallelic patients with suspected recessive IRD. Second, we will establish an integrated omics framework to accelerate diagnosis in unsolved IRD. Third, we will translate research findings to the clinic through ERN-EYE and patient advocacy organizations.
Our multidisciplinary approach involves ophthalmic genetics/genomics, (functional) genomics, bioinformatics, transcriptomics, proteomics, statistical genomics, and stem cell technology. Our expertise combined with a strong track record and international network offer a unique opportunity to address unmet needs and to pave the way to precision medicine in IRD.

Lay summary
Inherited retinal diseases represents major cause of certifiable blindness in the working age and childhood population. Despite a revolution in DNA technology that allowed to find genetic causes in half of the cases and that has culminated in successful gene therapies, essential knowledge is lacking to establish a genetic diagnosis in the remaining half of the patients, representing about 175.000 people in Europe.
With this project we aim to improve the discovery of hidden mutations in inherited retinal disease, often residing in the ‘dark matter’ of the genome, and to find novel targets for intervention. From blood cells of patients with undiagnosed inherited retinal diseases we will make stem cells that we will let develop to cells that mimic light-sensitive retina cells (photoreceptors) that express disease-causing genes of interest. We will perform large-scale DNA, RNA, and protein studies on these cells from patients and controls. By integrating these three layers of information, we will develop a sophisticated strategy to pinpoint hidden mutations in undiagnosed patients. These mutations may represent novel targets for intervention studies. This proposal has expected health impact, accelerating a definite diagnosis in inherited retinal diseases, improving genetic counseling, reproductive options, disease prognosis and management and ultimately offering therapeutic opportunities. We will transfer results from our study to the patients through our local clinical and international networks.