Novel Drug Therapy Partially Restores Hearing in Mice
A small-molecule drug is one of the first to preserve hearing in a mouse model of an inherited form of progressive human deafness, report investigators at the University of Iowa, Iowa City, and NIDCD. The study, which appears online in Cell, sheds light on the molecular mechanism that underlies a form of deafness (DFNA27) and suggests a new treatment strategy.
“We were able to partially restore hearing, especially at lower frequencies, and save some sensory hair cells,” said Dr. Thomas B. Friedman, chief of NIDCD’s Laboratory of Human Molecular Genetics and a coauthor of the study. “If additional studies show that small-molecule-based drugs are effective in treating DFNA27 deafness in people, it’s possible that using similar approaches might work for other inherited forms of progressive hearing loss.”
The seed for the advance was planted a decade ago, when NIDCD researchers led by Friedman and Dr. Robert J. Morell, another coauthor of the current study, analyzed the genomes of members of an extended family, dubbed LMG2. Deafness is genetically dominant in the LMG2 family, meaning that a child needs to inherit only one copy of the defective gene from a parent to have progressive hearing loss.
The investigators localized the deafness-causing mutation to a region on chromosome 4 called DFNA27, which includes a dozen or so genes. The precise location of the mutation eluded the NIDCD team, however.
A crucial clue to explain the DFNA27 form of progressive deafness arose from later studies of the mouse RE1 silencing transcription factor, or Rest, gene conducted by researchers at the University of Iowa. Dr. Botond Banfi and Dr. Yoko Nakano, lead authors of the current study, discovered that mouse Rest is regulated through an unusual mechanism in the sensory cells of the inner ear and this regulation is critical for hearing in mice. Because the human counterpart of the mouse Rest gene is located in the DFNA27 region, the Iowa and NIDCD researchers teamed up to reexamine the mystery of DFNA27 progressive deafness.