Identification of biomarkers reflecting opa1‐related dominant optic atrophy severity to infer patient cohorts eligible to clinical trials

Dominant Optic Atrophy is a blinding disease related to optic nerve degeneration, which is caused in more than 50% of cases, by a heterozygous mutation in the OPA1 gene. Since its molecular identification in 2000, one striking observation of DOA patients is the high variability of the visual defect, ranging from almost unaffected individuals to legally blind patients, even among relatives with the same mutation. This variability is further connected to a disease progression which is also highly variable, some patients evolving quickly to blindness, whereas others display a very slow progression. Together, this situation hampers the recruitment of OPA1‐related patients for clinical trials. To tackle this problem, we have recruited 100 OPA1 patients and 40 controls to identify biomarkers segregating with DOA severity. All patients and controls had a full ophthalmological examination and a mean follow‐up of 5 years, and all answered a visual quality of life and a nutritional questionnaire. Blood and stools were collected to perform transcriptomic, metabolomic and microbiota analyses. My talk will present the results of this multi‐OMIC analyses, the correlation between clinical and biological data and the identification of the most relevant biomarkers segregating with the evolution of DOA disease.