Otologic

Patient samples and mouse studies suggest that inhibiting REST or HDAC could help treat hearing loss associated with gain-of-function REST mutations. In a family with inherited progressive hearing loss, sequencing of a genetic locus previously linked with deafness identified an association between a mutant REST gene expressing a gain-of-function REST isoform and hearing loss. In mice, heterozygous expression of the REST mutation resulted in hearing loss, and in these mice, the HDAC inhibitor Zolinza vorinostat, which inhibits REST, decreased outer hair cell death and low-frequency hearing loss compared with vehicle. Next steps include testing additional HDAC inhibitors in mouse models of hereditary deafness...