Pharmacologic Regulation of Auditory Hair Cell Regeneration
Abstract
Post-mitotic mammalian hair cells (HCs) do not regenerate after traumatic damage, and their death leads to irreversible hearing and balance impairment. Therapeutically induced generation of new sensory HCs has been considered for many years. Yet, there are no available pharmacologic alternatives to trigger HC regeneration safely. Our laboratory uncovered the proliferative potential of quinoxaline (Qx), a non-steroidal anti-inflammatory compound, to regenerate lost HCs. During the past year, we focused on two series of Qx analogs to expand the structure of activity relationship of this novel chemotype, identify other proliferative analogs, and optimize potency, bioavailability, and in vivo efficacy. Two lead variants (Qx-294 and Qx-301)have been identified, showing promising in vitro ADMET ox profiles. Both compounds have been shown to have rapid absorption in zebrafish and induce supporting cell (SC) proliferation in the zebrafish neuromast and cochlea explants without signs of apoptosis. Overall, the results support the continuation of the studies in vivo in a mammalian (mouse) system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1191060
Entities
People
- Sonia M. Rocha-sanchez
Organizations
- Creighton University