Non-syndromic HSNHL occurs 1 in 1000 live births. Newborn hearing screening had been introduced around 2000; however, no effective therapy for SNHL has been developed. About 100 genes associated with non-syndromic HSNHL has been discovered: about 30 of these encode proteins associate with actin. We are intensively studying about Rho-family GTPases, which are key regulators for actin structures. During the study of hair cell-specific Cdc42-KO mice, we found that the activated RhoA signaling is one of causes of progressive SNHL in Cdc42-KO mice. RhoA is a regulator of DIA1, which is a key molecule in straight actin elongation and the responsible gene of the 1st type of autosomal dominant non-syndromic SNHL, DFNA1. We have discovered novel DFNA1 patients and clarified that DFNA1 is caused from constitutively active mutants of DIA1, in which the auto-inhibitory interaction is disrupted. Besides, patients with CDC42 mutants showing HSNHL were reported from Japan in 2015, and they are categorized into Takenouchi-Kosaki syndrome.
I will present recent advances of our studies regarding SNHL and our trial for development of novel drugs against SNHL.