Molecular and Transcriptomic Study Finds Potential New Targets for Therapies to Treat Noise-Induced Hearing Loss
Noise-induced hearing loss affects tens of millions of individuals in the United States. Yet, despite decades of research and advances in the mechanistic and molecular underpinnings of the disorder, there are still no FDA-approved medication regimens that can either prevent or slow the degenerative process or restore hearing function once lost.
However, new research from a multidisciplinary team of investigators led by University of Maryland Medical Center (UMMC) and School of Medicine (UMSOM) faculty have characterized and mapped the transcriptomic and signaling factors across the multiple cell types of the inner ear in the setting of acoustic trauma and noise-induced hearing loss (NIHL) in a murine model using single-cell RNA sequencing and other cell type-specific approaches. The research was published in September 2021 in the journal Cell Reports. The findings from the study provide researchers with a clearer understanding of the molecular changes that occur in the cells of the inner ear and may lead to targets for novel drug discoveries and translational research studying viable existing compounds targeting specific pathways or gene expressions. Furthermore, the results were disseminated to the scientific community through the gene Expression Analysis Resource, an online portal for sharing, visualization and analysis of genomic data, that was published by the senior author, Dr. Ronna Hertzano, MD, PhD, Tenured Professor of Otolaryngology-Head and Neck Surgery, Anatomy and Neurobiology and an affiliate member of the Institute for Genome Sciences, at the UMSOM.
Co-first authors of the new study were Beatrice Milon, PhD, from the University of Maryland, and Eldad D. Shulman, PhD, from the Sackler School of Medicine at Tel Aviv University in Israel. Collaborating teams include the team of Barbara Canlon, PhD from the Karolinska Institute, Sweden, and a team of investigators from Decibel Therapeutics.
Summary of Key Findings
The research team exposed animal models to noise-induced acoustic trauma and performed cell type-specific sequencing on cell types of the inner ear pre and post-acoustic trauma in order to better characterize the molecular processes at play and how they differed once the models experienced noise trauma.
After exposure, the models exhibited up regulation of the immune-mediated STAT3 and IRF7 transcription factors, and these factors were upregulated in all of the analyzed cell types.
Notably, the team also found cell-specific changes in transcriptional activity across a number of important pathways and cell types. Type 1A neurons, which are thought to be more noise-resilient, were found to have increased activity in the ATF3/ATF4 stress response pathway, while cells of the lateral wall showed down regulation in potassium transport genes.
The cell types, transcription factors, and molecular pathways identified could potentially lead to new therapeutic targets for further investigation to treat or prevent noise-induced hearing loss. Indeed, the study team found through further analysis a number of existing drugs that could be potentially leveraged against the transcriptomic pathways identified. Notable among the candidates are the diabetes drug metformin, cholesterol-lowering statins, and general anesthetics using halogenated compounds.
How UMMC Treats Patients with Noise-Induced and Age-Related Hearing Loss
UMMC treats all diseases of the ear and skull base. Treatment options include:
- All forms of hearing loss, including genetic, acquired, and trauma-related
- Diseases of the ear, including otosclerosis, glomus tumors, cholesteatomas, and tympanic membrane perforations
- Various approaches for hearing restoration, including hearing aids through bone conduction devices and a large practice of cochlear implantation
UMMC also has an active IRB for patients with suspected genetic hearing loss in which DNA is obtained from individuals and families for genetic analysis. This expertise is unique in that UMMC is equipped with three molecular ear and research labs associated with the department.
Refer a Patient
To learn more about how the Department of Otorhinolaryngology-Head and Neck Surgery at UMMC studies and treats acoustic trauma, noise-induced hearing loss, and other ENT conditions, and to refer a patient for evaluation or treatment, please contact 1-800-373-4111.
- Milon B, Shulman ED, So KS, et al. A Cell-type-specific Atlas of the Inner Ear Transcriptional Response to Acoustic Trauma. Cell Reports. 2021; 36: 10978.