de VRIEZE Eric
Development of a genetic therapy for DFNA9 adult-onset hearing loss
Project status: active
BACKGROUND
While hearing loss in adults is more often caused by factors such as noise exposure or ageing, genetic factors can also contribute. A number of genes have been linked to adult-onset hearing loss, including the gene COCH (cochlin). Mutations in the COCH gene lead to a type of hearing loss called DFNA9, a common form of inherited hearing loss. People with DFNA9 hearing loss typically start to lose their hearing as young to middle-aged adults and it worsens with time. They may also develop problems with their balance.
DFNA9 is a dominantly inherited form of hearing loss. This means that someone will develop hearing loss when only one of their two copies of the COCH gene (we inherit one copy from each parent) carries the mutation. The mutated copy of the gene leads to the production of toxic cochlin proteins. These toxic proteins interfere with the healthy cochlin proteins produced from the non-mutated copy of the gene.
A treatment that blocks the production of these toxic cochlin proteins should also protect the hearing of people at risk of this genetic form of hearing loss, or prevent worsening of their hearing loss. This would especially be the case if the treatment was given at an early age, before hearing loss begins to develop. The remaining cochlin proteins produced from the non-mutated version of the gene are enough for normal inner ear function and hearing.
Aims
AIMS
The researchers have created antisense oligonucleotides (ASOs), a type of DNA/RNA molecule. DNA is the material that genes are made from, and RNA is part of the process of producing proteins from the gene blueprint. These ASOs specifically target the mutated version of the COCH gene and prevent it from being used as a blueprint to make proteins, without interfering with the non-mutated version. They block production of the toxic cochlin proteins, so that only the healthy version of the protein is produced. Using these ASOs in the inner ear could slow or even stop the progression of hearing loss in people with DFNA9, providing them with a new treatment.
In this project, the researchers will further improve their ASO approach as a treatment for DFNA9 hearing loss. They will conduct experiments to show it is effective and safe for use in the inner ear. Their overall aim is to develop a new RNA-based therapy to prevent hearing loss in an adult-onset form of hereditary deafness, DFNA9.
Benefit
BENEFITS
The results from this project will provide important data to support future studies of this new genetic therapy towards approval for testing in clinical trials. If successful, their work will advance a new genetic treatment for DFNA9 hearing loss.
More generally, this project will provide the first proof of concept for the use of ASOs in the inner ear. This will open the way for this promising approach to be adapted to treat other forms of inherited hearing loss and prevent hearing loss in large numbers of people.
Dr Erik de Vrieze
MD/PhD
Radboud University Medical Center, Netherlands