Age Related Hearing Loss

Adeetee Bhide and Jianxin Bao

Department of Otolaryngology, Washington University School of Medicine

Auditory neurons such as hair cells and spiral ganglion neurons naturally die as we age, and since they cannot regenerate, this leads to age-related hearing loss. My lab is aiming to better understand the process through which auditory neurons die and develop cures for age-related hearing loss. In order to study auditory neuron loss, my lab is applying the confocal imaging method to study whether age-related loss of synaptic terminals between hair cells and spiral ganglion neurons contributes to loss of auditory neurons. Once this is known, clinical applications can be developed to address the primary problem. We believe that age-related hearing loss can be cured if we successfully make auditory neurons from somatic cells such as fibroblast or fat stem cells. We have devised two steps to achieve this goal: converting human and mouse cells into cells similar to embryonic stem cells (ESCs) and then making these converted cells into auditory neurons. Four factors (Oct4, Sox2, c-Myc, and Klf4) have been identified to be able to convert mouse cells into ESCs through retrovirus-mediated induction. However, these modified cells can form tumors in vivo. Thus, we are exploring two alternative methods to create the ESCs- transfection of plasmids and of mRNAs. For the plasmid, we are engineering a pIRES containing the genes Oct4, Sox2, c-Myc, and Klf4, which can then be transfected into mice fibroblast cells. For the mRNA transfection, we are engineering related genes into the pCMVTnT vector for making in vitro mRNAs. We will then transfect these mRNAs into somatic cells. If either of these methods results in cells similar to ESCs, we can then program the cells to form auditory neurons. If this project is successful, it will be very useful in clinical applications because, by using ESCs, we reduce the risk of the patient rejecting the cells or developing tumors. Furthermore, by creating ESCs rather than getting them from an embryo, we are able to avoid ethical concerns. Hearing loss is a stark reality for our rapidly aging population, and hopefully the techniques we are developing can be used by many in the future to again enjoy music and simple conversation.