Cochlea . Hair Cells . Hearing Loss

Inner EarResearch

Unravelling molecular mechanisms of auditory hair cell loss to find new therapeutic possibilities to treat hearing loss

Hearing loss has a huge impact on the affected individual as well as on our society.Not only is one baby out of 1000 born with hearing loss, but also more than50% of people older than 65 years suffer from hearing loss. Hearing loss of adult onset is one of the ten leading causes of disability-adjusted life years globally. It is estimated that 278 million persons worldwide suffer from disabling hearing loss (two-thirds of whom reside in developing countries). The impact of hearing loss on health care costs will very likely increase in the future considering the envisaged improvement in life expectancy.
The degeneration of inner ear sensory cells located in the cochlea, known as haircells underlies most forms of sensorineural hearing loss. Sensorineural hearing loss is difficult to treat, since it creates both loss of sensitivity and distortion. While hearing aids can increase sensitivity, they often do not overcome the distortion of sound caused by loss of hair cells. Therefore, in order to pave the road for new prophylactic and therapeutic approaches for sensorineural hearing loss, it is of the essence to thoroughly investigate molecular events involved in hair cell damage and death. Once we understand these molecular events we might try to block apoptosis signalling pathways while enhancing cell survival pathways, finally this will result in enhanced hair cell survival.
During the last couple of years, our research has been centered on the molecular mechanisms involved in hair cell damage and death. It has been demonstrated that signaling pathways exist that promote hair cell death and interestingly, it has also been shown that there are opposing pathways that promote hair cell survival. Different molecules have been found who influence these pathways, among them inhibitors who inhibit the JNK signaling pathway, apoptosis inhibitors, erythropoietin, somatostatin and octreotide which bind to the somatostatin receptor,and others. Also the phosphatidylinositol 3-kinase (pi3k) /Akt pathway has been studied in detail and its role in hair cell death and survival has been studied. Lately, we have founded a spin off company (Strekin AG, Basel) to explore pioglitazone and its effect on auditory hair cells. Currently, Strekin is running a clinical phase 2study to investigate whether pioglitazone can protect residual hearing during cochlea implant surgery.

Fig. 1: Transverse sections of the cochlear duct from adult wild type mice. Upper panel highlights the auditory inner and outer hair cells stained with myosin 7a antibody (Myo7a, green). Lower panel shows haematoxylin-eosin staining of cochlear structures. OHC, outer hair cells, IHC, inner hair cells.

Fig. 2: Whole mount staining of the middle turn of the organ of Corti from P4 mice highlighting the tree outer hair cells (OHC) and the inner hair cells (IHC) stained with myosin 7a antibody (Myo7a, green); and spiral ganglion neurons (SGN; β-III tubulin, red).

Fig. 3: Hair cell damage in the organ of Corti of neonatal mice induced by gentamicin. Phalloidin-stained hair cells from middle cochlear turn treated with and without gentamicin for 24 hours.