C: Therapy for the retina
Component C: Therapy for the retina
The visual impairment of USH patients often leads to almost complete blindness in the 3rd or 4th decade of life. So far no treatment to stop or slow down the retinal degeneration exists. However, the postnatal onset of the progressive retinal degeneration opens a time window for therapeutic intervention.Here we evaluate two strategies to re-induce USH genes expression of the missing USH protein.
First, we aim to develop a gene replacement therapy for USH2A (P6). Since the coding sequence of USH2A is to long for the cloning capacity of viral vectors, we will test the potential of short USH2A protein variants to rescue the photoreceptor degeneration in a pre-existing zebrafish ush2a mutant. Analysis of the rescuing effect of the minigenes will provide the basis for putative gene augmentation therapies in USH2A patients.
In parallel, we evaluate the read-through of nonsense mutations by translational read-through drugs (TRIDs) (P1). We will evaluate the potential of different TRIDs for targeting different nonsense mutations causing USH (USH1C and USH2A) and Senior–Løken syndrome, a syndromic ciliopathy associated with RP (nephronophthisis-4 gene, NPHP4). Furthermore, we will compare the biocompatibility of TRIDs and identify in vivo TRIDs delivery methods. Our ultimate aim isto save or (partially) restore visual function in patients.
European Research Projects on Rare Diseases driven by Young Investigators