Principal Investigator: Dr Adam Palermo
Decibel Therapeutics, Inc. (USA)Tags: 42738, featured, hearing, Therapeutics, tinnitus
Hearing loss imposes underappreciated health costs and deprives millions of many of the joys of life. Existing therapies are cumbersome and ineffective, but we lack knowledge about how to design better therapies that could address this public health burden. Human genetics has been shown as one route to help design better therapies: the DNA of every individual in the population is slightly different, and identifying differences that are over (or under) represented in people with hearing loss can suggest genetic causes of hearing loss. These, in turn, can be further investigated to suggest novel therapeutic strategies.
In this proposal, we will seek to identify genetic differences associated with hearing loss among UKBB patients. We will achieve this by, (a) systematically comparing the frequencies of DNA differences between people with normal hearing and those with poor hearing, to find those associated with hearing loss, and then (b) applying statistical approaches to link these differences to specific genes that could be targeted by a drug or other therapeutic strategy. We will focus on both unexpected associations that may emerge from this analysis – e.g. with genes never before expected to be involved in hearing – as well as associations within genes previous experiments suggest to be relevant to hearing.
We will also work to develop a method using genetics and other factors to predict who is at increased risk of hearing loss throughout life. This can help guide individuals at high risk to be more protective of their hearing, and may also be useful to help bring hearing therapeutics to the clinic.
We anticipate this project to take roughly two years. At its conclusion, we expect to have identified at least several genes that could be turned over to biologists to investigate whether they could yield effective therapies. We hope that this work can accelerate the timeline for making the joys and benefits of hearing available to everybody.
Scope extension February 2019:
We are interested in identifying genes that could be relevant to human hearing, with a focus on those that could be therapeutically targeted to prevent or reverse hearing loss. We will pursue two complementary approaches: first, by investigating whether variants nearby or with candidate genes demonstrate association with hearing-related phenotypes: second, by conducting a genome-wide association study with custom-defined hearing-related phenotypes and fine mapping of the identified associations. In addition, we will also seek to develop a genetic risk score (GRS) to predict risk of hearing loss.
We are interested in expanding the scope of our project to characterize the central neural processing changes that occur with tinnitus and hearing loss by analyzing fMRI data. Results from direct analyses of functional magnetic resonance imaging will be used both to identify potential objective biomarkers for tinnitus and hearing loss, as well as novel genes that elucidate the molecular pathways of these significant public health burdens. In a separate arm of the project, we will combine genetics and all phenotypic data to attempt to predict risk of both hearing loss and tinnitus. Better identification of patients at risk for these two serious maladies would be enabling for clinical studies in the field.
Last updated Mar 12, 2019