Preventing progressive hearing loss associated with Norrie disease

What is it about?

Norrie disease is a rare and severe genetic condition. It is caused by mutations in a gene called NDP located on the X chromosome and affects mainly boys. These boys are born blind or lose their vision in infancy and then also develop progressive hearing loss which can eventually become profound leading to deaf blindness. Recent work has shown that the hearing loss is associated with abnormal blood vessels in the cochlea (the hearing organ of the inner ear) as well as the death of sensory hair cells that detect sound vibrations in the cochlea and convert them into signals sent via nerves to the brain. We found that in mice with Norrie disease, treating just the faulty blood vessels is sufficient to halt the progressive loss of sensory hair cells and subsequent hearing loss.

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Photo by Laura Ohlman on Unsplash

Photo by Laura Ohlman on Unsplash

Why is it important?

We have recently shown that the Norrie deafness pathology is able to respond to gene therapy. Our current study investigated the mechanism of hearing loss in Norrie disease and identified a specific cell type, the vascular endothelial cells of the blood vessels, to which therapies could be targeted. The NDP gene encodes a protein called norrin. We showed that activation of a stabilized form of the protein β-catenin, which is thought to participate in the norrin signaling pathway in blood vessels, prevented outer hair cell death in the cochlea and hearing loss in a mouse model of Norrie disease. This is a step towards safe and effective clinical translation of a therapy, which would prevent the isolating dual-sensory deprivation experienced by people with Norrie disease. The study also highlights the importance of the vascular system to the normal functioning of the inner ear. The image shows the network of tiny blood vessels in the spiral shaped cochlea and the rows of sensory hair cells (in green) lining the coils of the cochlea.

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