Combating Sensorineural Hearing Loss

Sensorineural Hearing Loss (SNHL) is a widespread problem in the general population, reducing the quality of life for many people. In the article, “Mechanisms of sensorineural cell damage, death and survival in the cochlea” (Wong et al. 2015), the authors propose possible interventions for the unsolved problem of SNHL. There are many risk factors associated with SNHL including hypertension, certain drugs, infections, noise exposure, age (presbycusis), etc.. The breadth of these risk factors can cause relatively healthy individuals to develop some degree of SNHL within their lifetime, ranging in severity from mild to debilitating. What all of these factors have in common, is that they ultimately result in the death or damage of IHC and/ or SGN. Unfortunately, IHC do not regenerate. In development, some OHC will differentiate into IHC. However, these IHC do not proliferate after this point. According to the authors, this accumulation of risk factors can gradually damage hair cells over long periods of time, irreversibly deteriorating hearing. The authors argue that in order to combat SNHL, the best option is to discover new interventions to prevent it from occurring in the first place. These therapeutic interventions include antioxidants, anti-apoptotics, and proinflammatory cytokine inhibitors. 

While the methods proposed by Wong et al. appear promising for preventing SNHL, there is new evidence that it is possible to regenerate IHC after all. Jaime Garcia-Añoveros presented his new research to our school (Loyola University Chicago) this semester. He was a collaborator in the article, “Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1” (Wiwatpanit et al. 2018). His research shows a promising new direction to combat damage done to IHC after it has occurred. 

In Wiwatpanit et al. (2018), the authors demonstrate that mature OHC are capable of trans-differentiating into IHC via the manipulation of one gene. They manipulated the gene Insm1 in OHC. Insm1 encodes a zinc finger protein (INSM1) which prevents OHC from trans-differentiation into IHC during development. In the absence of INSM1 expression during development, OHCs mature into IHCs. In OHCs that lack INSM1 a set of genes is up-regulated which facilitate the transdifferentiation of the cell into the IHC phenotype. Furthermore, INSM1 expression makes the cell unresponsive to an IHC-inducing gradient, ensuring that the cell matures into an OHC. The authors conclude that the absence, of the Insm1 gene alone is sufficient to determine the differentiation of OHC into IHC. OHC typically express Insm1 gene, however, ablation of Insm1 from adult OHC promotes their transdifferentiation into IHC. This finding allows for mature OHC to be trans-differentiated into IHC via the manipulation of only a single gene. This has promising applications into treating SNHL in the future. 

While these two articles seek to correct SNHL, they have very different approaches. In Wong et al. (2015), they state that SNHL is irreversible. The authors propose methods for preventing SNHL before it occurs. While these are still very important topics of research to explore, they do not propose possible solutions for treating SNHL after its onset. In contrast, the applications of Wiwatpanit et al. (2018) exclusively focus on correcting SNHL after IHC damage occurs. Since SNHL is so widespread, both of these articles provide invaluable knowledge for improving the quality of life of many people. With both of these articles in mind, I am optimistic that there is very promising clinical treatments for SNHL coming in the near future. We have insights into both the prevention and reversal of IHC damage. Hopefully this information will help eliminate SNHL in the future. 

References: 

• Wiwatpanit, T., et al. (2018). Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1. Nature 563, 691–695. doi:10.1038/s41586-018-0570-8 
• Wong, A., Ryan, A. (2015) Mechanisms of sensorineural cell damage, death and survival in the cochlea. Frontiers in Aging Neuroscience 7:58. doi: 10.3389/fnagi.2015.00058