WP 2.1: Pathologies génétiques sensorielles

Coordonnateur: Hélène Dollfus 

Co-coordonnateur: Vincent Marion

General scopes and previous achievements:

Genetic diseases, affecting neurosensory organs and inducing disabilities such as deafness or visual impairment (i.e: Inherited Retinal Degenerations IRD), have been a major topic developed since 2002. Indeed clinical research has been performed on syndromic IRD especially for a recently defined group of diseases, the ciliopathies like Bardet-Bield (BBS) and Alström (ALMS) syndromes. For both, we have characterized in depth the neurologic/psychiatric and retinal phenotypes. CARGO is leading two national RADICO rare disease cohorts namely RETICO and COBBALT. CARGO is one of the 3 teams involved in the first national forfeit d’innovation plan for artificial retinal implantation for IRD patients. 

Scientific research has enabled since 2006: 6 novel genes identifications using Next Generations Sequencing strategies. Cellular and animal modelling have enabled better pathogenesis knowledge in particular for IRD. Translational research has showed therapy developments such as pharmacological compounds to slow retinal degeneration in ciliopathies (with the use of valpro・ acid combined to guanabenz).

Future projects in NEUROGENYCS:

Clinical research: Innovate and develop Deaf Blind Patient health monitoring with “human machine interfaces” including psychocognitive impact studies (EU project in preparation). Study RETICO and COBBALT cohorts to determine the best efficient biomarkers for clinical trials to be set in the next 5 years. Identify genomic biomarkers for genotype-phenotype modifications by way of NGS with platform 3.

Fundamental research: Study CNS involvement for the ciliopathy related obesities (using our conditional Bbs and Alms mice with the ICS). Determine in depth pathogenesis of photoreceptor degeneration including biomarker identification. Model photoreceptor cells by way of iPS cells derived from patients and improve ciliopathy related RD modelling with small or large animal. For novel gene identification, we wish to develop a NGS mutation validation platform using all tools including short life animal models.

Translationnal research: Therapies to cure retinal degeneration in ciliopathies by a general neuroprotective agent or gene derived strategies (gene replacement or read-through or exon skipping).