This is an RNID-FPA Translational Research Grant awarded to Professor Jane Sowden at University College London, Institute of Child Health in 2022. We’re funding this grant in partnership with Fondation Pour l’Audition.
Norrie disease is a rare genetic condition caused by changes in a gene called NDP. NDP contains the blueprint to produce a protein called Norrin. Norrin is an important molecule that directs the development and organisation of blood vessels in the eye and ear. The blood vessels supply the eye and ear with nutrients and other important chemicals so that they can work correctly.
People with Norrie disease carry changes in their NDP gene that means they don’t produce Norrin protein. This means that the blood vessels in the eye and ear don’t form or work correctly. Boys are more usually affected than girls; children with Norrie disease are born blind, and many will also begin to lose their hearing from around the age of 12. The combined effect of losing both their sight and their hearing has a severe impact on their quality of life, social interactions and independence.
Currently there is no treatment for Norrie disease. At the moment, children with Norrie disease who develop hearing loss are offered hearing aids, and cochlear implants once their hearing loss becomes severe. However, these devices have limitations, especially given the children’s blindness, and do not fully restore natural hearing.
The researchers have previously studied mice that have been genetically modified so they do not produce Norrin protein, in the same way as people with Norrie disease. To understand the cause of hearing loss in Norrie disease, they studied the effects of losing the Norrin protein on the inner ears of the mice. The scientists also discovered that they could use gene therapy to carry the original version of NDP into the inner ear of these mice. This gene therapy was able to reduce damage to the inner ear and prevent the mice’s hearing loss.
In this project, the research team will work on a gene therapy to carry the original version of NDP into the inner ear of these mice. With our funding, the scientists will perform experiments that are needed to advance this promising new gene therapy towards the clinic. They will produce their gene therapy molecule so that it can be used in people, and be delivered directly to the inner ear to replace the missing Norrin protein. They will then measure how effective the therapy is at preventing hearing loss in young mice with Norrie disease, an important step before it can be tested in people.
The team of researchers will use the results of this project to support their application for permission to start a clinical trial in people with Norrie disease. If successful, this research will advance a new genetic-based treatment for hearing loss in Norrie disease. It could ultimately be used to slow down or prevent hearing loss and reduce the impact of Norrie disease on affected people.
More generally, this project could be an important proof of concept for the use of gene therapy in the inner ear. It could open the way for this promising therapeutic approach to be adapted to treat other forms of inherited hearing loss, potentially preventing hearing loss in large numbers of people.