Year Identified: 1998
Each research project listed below will include a graphic of the research continuum. The gold box indicates where this project falls on the continuum, illustrating its progress towards reaching people living with Usher syndrome, from "Bench to Bedside."
RUSH2A Natural History Study
According to Dr. Jacque Duncan, RUSH2A Study Chair, "Natural history studies are important to prepare investigators to design clinical trials. It's essential to know how vision is affected in patients with USH2A mutations in order to determine what to measure and how much change we expect to see over time, in order to know whether a potential treatment improves the vision or decreases the rate of vision loss in the long run."
ProQR's Stellar Clinical Trial
STELLAR or PQ-421a-001, is a first-in-human study that will initially include approximately 18 adults with vision loss due to mutations in exon 13 of the USH2A gene and will be conducted at about seven expert sites in North America and Europe. QR-421a is designed to exclude exon 13 from the USH2A mRNA, thereby removing the mutation in exon 13. This approach is also known as exon skipping. RNA is the "blueprint" for protein synthesis, and the skipping of exon 13 in the "blueprint" is expected to lead to a shortened but functional Usherin protein.
Pre-clinical USH2A c.2299delG mutation gene editing using the CRISPR system
Carla Fuster Garcia, Ph.D. and her team at Instituto de Investigación Sanitaria La Fe in Valencia, Spain have successfully investigated CRISPR/Cas9 gene editing in USH2A c.2299delG mutation on fibroblasts. In vitro mutation repair was demonstrated to be successful. The proven effectiveness and specificity of these correction tools indicate that the CRISPR system should be considered to further explore a potential treatment of Usher syndrome.
AON-based splice correction for the USH2A deep intronic c.7595-2144A>G mutation
Erwin van Wijk, Ph.D. and his team at Radboud University Medical Center Nijmegen in the Netherlands are utilizing an AON-based splice correction as an approach for the development of a future treatment for USH2A-associated Retinitis Pigmentosa caused by the deep-intronic c.7595-2144A>G mutation.
Watch Dr. van Wijk's USH Talk about this approach
USH2A-Related Science News
ProQR Therapeutics announced that the FDA has cleared the Investigational New Drug (IND) application for QR-421a. QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of the vision loss associated with Usher syndrome type 2 and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. ProQR plans to start enrolling patients in a Phase 1/2 trial named STELLAR in the coming months with preliminary data expected in mid-2019.
In this USH Talk, Dr. Hannie Kremer explains genetic testing of the USH2A gene, as conducted at the Radboud University Medical Center in Nijmegen, Netherlands.
In this USH Talk, Dr. Erwin van Wijk shows that AON-based splice correction could be a promising approach for the development of a future treatment for USH2A-associated retinitis pigmentosa caused by the deep-intronic c.7595-2144A>G mutation.
Our latest USH Talk features researcher Dr. Jacque Duncan from the University of California, San Francisco. Dr. Duncan shares an overview of an upcoming clinical trial that aims to study the rate of progression of USH2A related retinal degeneration: The RUSH2A Study.
Researchers study genotype–phenotype correlations and compared visual prognosis in Usher syndrome type IIa and nonsyndromic RP.
Researchers investigated the proportion of exon deletions and duplications in PCDH15 and USH2A in 20 USH1 and 30 USH2 patients from Denmark.
Foundation Fighting Blindness' deputy chief research officer, Dr. Brian Mansfield, explains how retinal researchers are working with induced pluripotent stem cells (iPSC), a patient's own skin cells, to gain a better understanding of the RP caused by defects in the gene USH2A. This basic research provides critical information for developing future treatments.
Steele-Stallard, Le Quesne Stabej P, Lenassi E, Luxon LM, Claustres M, Roux AF, Webster AR, Bitner-Glindzicz M..
Screening for duplications, deletions and a common intronic mutation detects 35% of second mutations in patients with USH2A monoallelic mutations on Sanger sequencing. An overview of a study to improve the molecular diagnosis in families with USH2A by screening USH2A for duplications.