Usher Syndrome is a rare, inherited condition that affects the three major senses, vision, hearing and balance. There are three types and they are:
Type 1—This causes profound deafness at birth, balance dysfunction and progressive vision loss.
Type 2—This causes moderate to severe hearing loss at birth and progressive vision loss.
Type 3—This causes later onset progressive hearing loss and progressive vision loss.
This condition affects at least 25,000 people in the U.S. and over 400,000 worldwide. Of course, research is ongoing for treatments and ultimately a cure for Usher Syndrome. One such project involves RNA therapies to treat adults with Usher Syndrome. ProQR Therapeutics N.V. of the Netherlands, completed a Phase 1/2 clinical trial of the drug QR-421a. This drug showed benefits on many measures of vision, including visual acuity and visual fields as shown in optical coherence tomography retinal imaging after a single dose in both advanced and early-moderate Usher Syndrome patients. No serious adverse events were reported and based on these finding, the company planned to do a Phase 2/3 trials at the end of 2021.
QR-421a’s purpose is to stop vision loss or restore vision in persons with a mutation in a specific part of the USH2A gene, known as exon 13. The drug works by binding to the mutated USH2A RNA and excludes exon 13 from the RNA. This is known as exon skipping and as a result, the cells in the retina produce a shorter but functional USH2A protein. Currently, there are no approved treatment for Usher Syndrome, so these finding suggest that QR-421a has the potential to stop disease progression and maintain vision.
Other research at the University of Maryland School of Medicine involved a retinoid therapy that improved vision in mice with Usher Syndrome. While it isn’t a cure, this therapy has been shown to improve the function of the remaining tissue. This therapy works on the PCDH15 gene. Researchers previously identified that a mutation in the PCDH15 gene lead to a shortened version of the protein protocadherin-15. What lead to the blindness from this mutant protocadherin was unknown.
Over time, scientists identified two functions of protocadherin-15. First, it helps the light-dark cycle proteins move between the different compartments of the light-detecting photoreceptors in the eye. Second, protocadherin-15 is required for recycling molecules needed for functioning eye tissue, the retinoid. The mice with Usher Syndrome type 1F had reduced levels of retinoid in a certain kind of eye cell.
When the retinoid drug was given to the mice with Usher Syndrome, there was increased electrical activity in the eyes of both young and adult mice, which shows improved visual function. There are currently FDA approved drugs that are similar to the retinoid drugs used in this study and researchers hope to partner with one of these companies in order to start a clinical trial in patients with type 1F of Usher Syndrome to see if it can prevent continuing vision loss.