Kerstin Nagel-Wolfrum from Mainz (Johannes Gutenberg University, Germany) is doing research into ‘translational read-through’ therapy for USH1C as a result of stop (nonsense) mutations in the USH1C gene.

Many mutations causing Usher Syndrome are ‘nonsense mutations’. This means that the mutation prematurely stops the protein production process, a so-called ‘stop sign’. Nagel-Wolfrum studied read-through medicines (abbreviated by TRID = Translational Readthrough Inducing Drug), as a possible therapy for USH1C. These ‘read-through’ medicines can make the protein production machine ignore the ‘stop sign’ and so make the machine produce the complete protein. TRID medicines have existed for some time already, but they often have adverse effects on the body.

Nagel-Wolfrum is looking for new TRID medicines with fewer side effects. She studied the medicine Ataluren in cultivated cells with a USH1C mutation. Without treatment these cells are unable to produce the USH1C protein harmonin. When Ataluren is administered to the cultivated cells with a USH1C mutation, the complete harmonin protein is produced again.  In order to investigate whether Ataluren is also effective in the eye, studies are presently conducted into pigs with a mutation in the USH1C gene. Nagel-Wolfrum also treated mice with another form of retina degeneration with Ataluren eye drops. This slowed down the retina degeneration. At this moment clinical trials are conducted with Ataluren for Aniridia, an eye disease which prevents the proper forming of the iris. For USH1C the studies with the pigs will have to demonstrate whether Ataluren can also slow down the retina degeneration before clinical studies can be done.