Hair Cell Regeneration and Treatment for Noise-Induced Hearing Loss in Pig Model
Abstract
Regeneration of hair cells in fully mature mammalian inner ear is a key application for potential therapy to treat hearing loss. Adult mouse inner ear can be reprogrammed by coactivation of c-Myc and Notch1 genes, enabling adult cochlear cell types to re-enter cell cycle. Reprogrammed adult cochlear supporting cells are sensitized by transient Myc/Notch activation and respond to hair cell induction signals by overexpression of Atoh1, a hair cell fate determinant, and transdifferentiate into hair cells efficiently in vitro and invivo. Our study further identified a pathway mTOR and showed its activation by gene manipulation resulted in robust attenuation of noise-induced hearing loss (NIHL). To move hair cell regeneration towards the clinic, reprogramming needs to be achieved by a clinically relevant method instead of transgene manipulation in the mouse models. A large animal pig model will be extremely valuable in developing a clinically relevant program in hair cell regeneration, due to the similarities between the pig and human inner ears in development, anatomy and physiology. In addition, we have identified a pathway with an FDA approved drug that potently attenuates NIHL. The drug could be developed into a treatment program for NIHL in the pig model and expand it to the applications in humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1223404
Entities
People
- Ying Wang
- Zheng-Yi Chen
Organizations
- Massachusetts Eye and Ear Infirmary
- Walter Reed Army Institute of Research