Italian Project on Hereditary Optic Neuropathies (IPHON): from genetic basis to therapy

Descrizione del progetto

Hereditary optic neuropathies (HON) are common causes of vision loss, with about half of the patients without genetic
definition. Furthermore, there is only one approved drug (Idebenone) as therapeutic option. HONs are largely associated
with mitochondrial dysfunction and most known genes encode mitochondrial proteins. In the present project, to identify new
genes, we will sequence the genome coding regions by whole exome sequencing (WES) in over 200 HON patients,
negative for common mutations. The pathogenicity of mutations in new genes will be tested by their modeling in yeast
Saccharomyces cerevisiae. Mitochondrial functions will be also evaluated in patient-derived fibroblasts. Clinical phenotype,
in particular neuro-ophthalmological, will be systematically investigated. Taking advantage of the yeast model, a library of
FDA approved drugs, will be screened to identify therapeutic options to be translated into patients.