Dr Yoshikazu Imanishi of Case Western Reserve University in Cleveland (Ohio, USA) is focusing on the development of therapy for Usher Syndrome 3A.
One of the most frequent mutations in USH3A is the N48K mutation.
Imanishi studies the clarin-1 protein with the N48K mutation in cultivated cells.
This study demonstrated that the N48K mutation makes the clarin-1 protein unstable and this leads to the cell quickly destroying the clarin-1 protein again. As a result of this instability, the rods and cones of patients with the N48K mutation in USH3A show a lack of functional clarin-1 protein.
Subsequently, Imanishi used cultivated cells to look for medicines that can stabilise the N48K clarin-1. The medicine BF844 appeared to stabilise N48K clarin-1 in the cultivated cells.
Imanishi then administrated this medicine to mice with the N48K mutation in the USH3A gene. It was shown that BF844 has a therapeutic effect on the loss of hearing in mice with the N48K mutation: the mice treated with BF844 could hear better than their brothers and sisters that carried the N48K mutation but were not treated with the medicine. The N48K mice do not show any retina degeneration.
The IND application for a trial of the drug BF844 is currently being prepared for the FDA. A trial will start in 2020/2021 for the specific mutation N48K in the USH 3 gene.