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Spring Seminar Series

March 11, 2020 @ 12:00 pm - 1:00 pm

Will McLean, PhD
Co-Founder, Frequency Therapeutics

“FX-322, A Potential Small Molecule Combination Therapy for Sensorineural Hearing Loss”

Room 3571 WIMR I

Dr. Will McLean, Frequency Therapeutics


Hearing loss is commonly caused by loss of cochlear hair cells after noise or other trauma. Currently, only devices (e.g. hearing aids) exist to treat hearing loss, which do not restore the underlying cellular deficit that causes the disease. Unlike other species, mammals lack the ability to regenerate hair cells. Although previous work showed that mammals have putative hair cell progenitors after cochlear development is complete, these cells fail to divide and differentiate on their own to repair damaged tissue.

In order to screen compounds that would promote regenerative behavior, cochlear hair cell progenitors were isolated from mice and cultured in a 3D organoid system. Individual and combinations of compounds were tested for promotion of progenitor cell proliferation and subsequent differentiation into hair cells. A combination of two compounds that activate the Wnt pathway and inhibit histone deacetylase (HDAC) was found to greatly expand otherwise senescent hair cell progenitors. This combination generated additional hair cells in intact cochleae ex vivo, without the need for differentiation agents. These compounds (CHIR99021+VPA) may serve as a likely candidate to promote hair cell regeneration in vivo. This combination, formulated and named as FX-322, recently completed a Phase I safety trial in cochlear implant patients and a Phase I/II safety trial in patients with mild to moderately severe sensorineural hearing loss and showed no serious adverse when delivered intratympanically. In the Phase I/II trial, a subset of FX-322 treated patients demonstrated hearing improvement based on audiologic measures.


March 11, 2020
12:00 pm - 1:00 pm
Event Category:


WI United States