The National Center for Genomic Analysis (CNAG), located at the Barcelona Science Park, is collaborating in a study led by researchers from the University of Barcelona (UB) and the Bellvitge Biomedical Research Institute (IDIBELL) that identifies the genetic mechanisms involved in a disorder affecting the vestibular system of the ear, which is key to maintaining balance and hearing ability. The study, published in the Journal of Biomedical Science, shows how the degradation of these non-regenerative cells begins with the continued use of certain antibiotics and drugs.

Certain drugs and chemicals can damage the vestibular system, which is essential for hearing and balance. Prolonged use of toxic substances, such as some antibiotics (for example, streptomycin used in tuberculosis relapses) or certain anticancer drugs, can damage the hair cells that form part of this system. In mammals, these cells have a very limited capacity for regeneration, so chronic exposure can lead to permanent sensory loss. Instead of dying immediately, hair cells can be “expelled,” a controlled process in which they leave the sensory epithelium and move into the fluid-filled cavity of the inner ear. Before this happens, subtle changes occur, such as the weakening of connections with nerve cells and the disruption of specialized structures that maintain hair cell function.

Now, new research has identified the genetic mechanisms involved in the degradation of the vestibular system caused by ototoxic compounds that affect the vestibule. The study found that one of the earliest and most consistent responses is the decrease in the activity of hair cell–specific genes, which implies a reduction in the expression of genes essential for their function. Among these are Atp2b2 and Xirp2, which help maintain the structure of the stereocilia (the tiny hair-like projections that detect sound and head movements); Nsg2, which is important for communication between hair cells and nerve cells; and Kcnab1 and Kcna10, which control the ion channels that allow electrical signals to pass through the cells.

The main causes of chronic vestibular ototoxicity are antibiotics from the aminoglycoside family, such as streptomycin, which is used in cases of tuberculosis relapse, or anticancer drugs such as cisplatin. The continued use of these medications triggers a degeneration process that causes “hair cells to detach from neurons, begin to deform, and eventually be expelled from their place in the sensory tissue,” explains Jordi Llorens, lead author of the study and researcher at the Faculty of Medicine and Health Sciences of the University of Barcelona (UB), and researcher at the Institute of Neurosciences (UBNeuro) and IDIBELL.

To uncover these early genetic changes, the study used RNA sequencing, a technique that measures global gene expression and reveals which genes are activated or silenced in the tissues of the vestibular system. Marta Gut, Head of the Sequencing Unit at CNAG, together with members of the Functional Genomics Team, Anna Esteve-Codina and Beatriz Mur, contributed to the sequencing and analysis of this project.

Using this approach, the study also showed that hair cells respond to chronic ototoxic stress by activating stress-related genes and adjusting processes such as cell adhesion, energy production, and protein handling. Understanding these early molecular changes provides valuable insights into the mechanisms that cause hair cell loss and could help develop strategies to protect hearing and balance before permanent damage occurs. More specifically, these findings could also help improve the diagnosis of chronic vestibular ototoxicity and other pathologies related to the hair cells of the vestibular system.

» Article de referència: Borrajo, M., Greguske, E.A., Maroto, A.F. et al. Early downregulation of hair cell (HC)-specific genes in the vestibular sensory epithelium during chronic ototoxicity. J Biomed Sci 32, 84 (2025). doi: 10.1186/s12929-025-01180-4

» Link to the news: CNAG website [+]