Development and evaluation of the efficacy of gene therapy in a patient-derived inner ear organoid model for hearing loss caused by pathogenic mutations in the gene TMPRSS3

• Applicant: Dr. Thore Schade-Mann
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544948147

Hearing loss is the most common sensory deficit and leads to considerable health and socio-economic burdens. In early childhood hearing loss, about 50% of cases can be attributed to pathogenic mutations. To date, there is no causal therapy for hearing loss. One of the most frequently affected genes is TMPRSS3. This project aims to uncover the mechanism that leads to hearing loss in this gene. Furthermore, a new gene therapy approach for patients suffering from TMPRSS3-induced hearing loss will be tested. For this purpose, a new, patient-specific inner ear organoid model will be used: Mononuclear cells are isolated from peripheral blood of affected patients, from which induced pluripotent stem cells are generated. These stem cells are then differentiated into inner ear organoids. The pathophysiology of the affected patients can then be investigated and a patient-specific gene therapy can be tested.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Hosts: Professor Karl R. Koehler, Ph.D.; Professor Eliot Shearer, Ph.D.