Human Inner Ear Organ-On-Chip Platforms for Hearing Loss Drug Discovery
Abstract
Hearing is pivotal for human verbal communication, social interactions, and general alertness to our surroundings. impairment, as a consequence, has a profound effect on quality of life. In children, it may result in learning disabilities and difficulties in acquisition of a spoken language. In adults, it can affect work performance and result in social isolation and depression. Exposure throughout life to infections, the side-effects of some medicines, and noise overexposure result in hearing impairment. Occupational loud noise exposure (prolonged or blasting) is particularly relevant for the military units, where high proportions of service-connected disabilities are reported. Specialized sensory cells located into the inner ear translate with remarkable speed and accuracy sound-induced vibrations of different loudness and pitch into chemical signals that can be interpreted by the brain as sound. It is specifically the loss of these sensory cells that results in permanent hearing loss. The human ear in fact cannot repair after damage. Novel therapies are being developed to protect these vulnerable cells and boost their regeneration. Too often, however, exciting findings obtained in animal studies do not translate to patients, either because of the differences in the response to therapies between species, or due to the high costs associated with clinical trials, which leaves many novel candidate therapies idle. We believe experimental models based on human cells will bridge this gap and promote the advancement of therapies for hearing loss. This research project focuses on the development of a human-specific in-a-dish model to study how key cell types required for hearing are formed and which factors may cause their damage and result in hearing impairment. In addition, the generated cells will be used to validate new drugs for hearing restoration. As the human ear is inaccessible for experimental purposes, we will exploit an alternative strategy, based on the generation of human inner ear sensory cells from a unique source of stem cells, the so-called induced pluripotent stem cells. These can be generated in the laboratory and converted to different cell types to study organ biology and disease. Through an intercontinental collaboration of two laboratories with key expertise in hearing research and stem cell biology, we will test complementary approaches to create an in vitro model of the human hearing organ. We will optimize the methodology to generate auditory cells and through knowledge exchange implement the reproducibility of the findings. These studies will pave the way for the identification of novel hearing loss therapeutics. Specifically, testing the efficacy of new therapies on patient-derived cells will increase the confidence among stakeholders and streamline clinical translation. We have confidence that this will reflect in lower costs for drug development, resulting in more inclusive treatment options.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110810
Entities
People
- Karl Koehler
Organizations
- United States Army