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Hearing loss

g-Secretase; notch 1 (NOTCH1)

Studies in cell culture and in rodents suggest blocking NOTCH1 processing using g-secretase inhibitors could help treat hearing loss. In cultured inner ear stem cells and inner ear tissue explants, small molecule inhibitors of g-secretase induced growth of middle ear hair cells, which are damaged in noise-induced hearing loss. In mouse models of hereditary and noise-induced hearing loss, local or systemic delivery of a g-secretase inhibitor caused the regrowth of hair cells and restored hearing. Next steps could include optimizing dosage and delivery to minimize toxicity of g-secretase inhibitors.
Audion Therapeutics B.V., cofounded by the study's leader, and Inception 3 Inc., have preclinical compounds to treat hearing loss (see γ-Secretase lost and sound, page 7).

SciBX 6(2); doi:10.1038/scibx.2013.40
Published online Jan. 17, 2013

Patent pending; licensing status undisclosed

Mitzutari, K. et al Neuron; published online Jan. 9, 2013;
Contact: Albert S.B. Edge, Harvard Medical School, Boston, Mass.