Why is Genetics Important in Hearing?
The cochlea, a part of the inner ear, is a spiral shaped organ containing 30,000 sensory cells evolved to help us hear. Each cell, called a hair cell, has hundreds of thousands of working proteins that enable us to convert nanometer-scale movements into electric neural signals. The structures of these proteins are based on the script provided by our DNA, a copy of which is found in nearly every cell in our body. The entirety of an individual’s DNA is known as a genome, which can be thought of as an instruction set for the human body. Each line, known as a gene is the basic unit of heredity. Some genes encode proteins. A change in our DNA can result in a protein that is unable to perform its typical role. As a result, these DNA changes, in thousands of different ways, can affect the ability to hear.
How do we know this?
Every year, thousands of children are born deaf or hard-of-hearing in the United States and Europe. Approximately 80% of congenital hearing loss in the United States and Europe is sensorineural hearing loss due to genetic causes. To date, more than 150 genes are known to be directly linked to deafness. By comparing genetic data between deaf and hearing family members, scientists have been able to learn the identity and location of these deafness-related genes. By identifying these genes and understanding the functions of the proteins they encode, scientists can begin working to develop treatment options. One type of gene therapy aims to deliver a healthy piece of DNA to cells in the cochlea, enabling them to produce functional protein and restore hearing.
How can we get from here to a potential therapy?
To develop treatments for hearing loss and deafness, Akouos is bridging the scientific community’s growing understanding of hearing loss genetics with recent advances in gene therapy. First, we need to understand which genes are affected and how they impair hearing. Healthy copies of these genes can be encased in engineered viral vectors to enter relevant cells and enable them to produce functional proteins. We are currently conducting preclinical studies to support initial clinical trials that will assess the safety and efficacy of a gene therapy for individuals with sensorineural hearing loss due to mutations in the otoferlin (OTOF) gene.
Hearing Loss Registry
Together with leading clinicians, researchers, and their medical institutions, Akouos is proud to sponsor the Sing (sensorineural genetic) hearing loss registry. The aim of the Sing Registry is to establish the global infrastructure required to assess hearing loss genotype-phenotype relationships and intervention outcomes over time.