Otoferlin-Related Auditory Synaptopathy: Disease Mechanisms and Preclinical Development of Gene Therapeutic Approaches (A04)

• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Experimental Models for the Understanding of Nervous System Diseases ; Otolaryngology, Phoniatrics and Audiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 528760423

Synaptic disease mechanisms contribute to sensorineural hearing impairment, with otoferlin mutations being the most prevalent cause of inherited auditory synaptopathy. This project aims to decipher otoferlin-related synaptopathy by comprehensive analysis of impaired synaptic sound encoding in CRISPR/Cas9 mouse models of human missense mutations. In parallel, we plan to refine viral vector-mediated gene therapy for restoring hearing by supplementing residual otoferlin levels.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1690: Disease Mechanisms and Functional Restoration of Sensory and Motor Systems
• Applicant Institution: Georg-August-Universität Göttingen
• Project Heads: Dr. Kathrin Kusch; Professor Dr. Tobias Moser