New Research Sheds Light on Genetic Mechanisms of Inherited Deafness
Understanding the Genetic Basis of Progressive Hearing Loss
Recent studies in mice have unveiled significant genetic mechanisms underlying inherited deafness, potentially paving the way for new treatment strategies in humans. Approximately a decade ago, scientists at the National Institute on Deafness and Other Communication Disorders identified a group of genes known as DFNA27, which are linked to progressive hearing loss when mutated.
New Findings from the University of Iowa and NIH
A collaborative research team from the University of Iowa and the National Institutes of Health has made further advancements in understanding these mutations. Their findings were published in the journal Cell. During their investigation, the researchers focused on a gene named REST, which plays a crucial role in regulating sensory cells within the inner ear. These hair cells are vital for hearing as they detect auditory stimuli.
Impact of REST Gene Modification in Mice
When the researchers deleted a specific coding sequence of the REST gene in mice, they observed the death of inner ear hair cells, resulting in deafness. This particular sequence, known as exon 4, functions as a molecular switch that activates genes that promote hair cell survival when present, but leads to cell death when suppressed.
Restoring Hearing Through Pharmacological Intervention
Building on their findings, the team further investigated the REST gene’s inhibitory process by employing small molecule drugs. The administration of these drugs to the mice resulted in partial restoration of hearing.
Clinical Implications and Future Directions
These findings hold significant clinical promise, particularly since the human equivalent of the REST gene is part of the DFNA27 gene group associated with inherited deafness. The authors emphasize the critical nature of this basic research in uncovering molecular mechanisms and express hope that these discoveries will inform future treatment plans for progressive hearing loss in humans.
References
– Novel drug therapy partially restores hearing in mice. National Institutes of Health. https://www.nih.gov/news-events/news-releases/novel-drug-therapy-partially-restores-hearing-mice. Published July 2, 2018.
– Nakano Y, Kelly MC, Rehman AU, Boger ET, Morell RJ, Kelley MW, Friedman TB, Bánfi B. Defects in the Alternative Splicing-Dependent Regulation of REST Cause Deafness. Cell. 2018 Jul 26;174(3):536-548.e21. doi: 10.1016/j.cell.2018.06.004. Epub 2018 Jun 28.