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.
- Link to study details on ClinicalTrials.gov
- View presentation on this study from the USH2019 Connections Conference
- Watch Dr. Hester van Diepen's USH Talk about ProQR's Development Pipeline
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.
USH2A-Related Science News
21 pathogenic mutations in the USH2A gene have been identified in 11 Chinese families by using the targeted next-generation sequencing (NGS) technology. We identified 21 pathogenic mutations, of which 13, including 5 associated with RP and 8 with USH II, have not be been previously reported. Visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations. These findings provide a basis for investigating genotype-phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.
What this means for Usher syndrome: This study provides additional genetic information about Usher syndrome type 2.
How do you cope with living with Usher syndrome? What strategies do you use to overcome challenges? In this USH Talk, Dr. Moa Wahlqvist summarizes the findings from the first qualitative scientific study of its kind, exploring the strategies described by 14 people with Usher syndrome type 2 seeking to remain active agents in their own lives.
ProQR Therapeutics N.V., a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, today announced the first patient treated in the Phase 1/2 STELLAR clinical trial for QR-421a in patients with Usher syndrome type 2 or non-syndromic retinitis pigmentosa (RP). Interim data from the trial are expected to be announced by mid-2019. According to David G. Birch, Ph.D., Principal Investigator of STELLAR and Scientific Director of the Retina Foundation of the Southwest in Dallas, Texas, “The STELLAR study is one of the first studies of its kind exploring the impact of ProQR’s RNA therapies on patients with Usher syndrome type 2 due to an Exon 13 mutation. The STELLAR trial will explore whether QR-421a (ProQR’s RNA therapy) can slow disease progression or even reverse it.”
What this means for Usher syndrome: There may be a potential drug available to reverse blindness caused by Usher syndrome.
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.
ProQR Therapeutics N.V. announced the results for their clinical trial of QR-110 LCA 10 is on track, and eight out of twelve patients have been enrolled in a Phase 1/2 trial. The results for safety and efficacy for the trial are expected to be announced in the second half of 2018. Currently, they planing to announce data from a QR-421 study for Usher Syndrome. The organization has received $7.5 million in funding from the Foundation Fighting Blindness (FFB) and hopes to use QR-421a for Usher Syndrome Type 2A to target mutations in exon 13.
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.
Jennifer Phillips, Ph.D. recaps ARVO 2017 Day 2 with highlights on Usher syndrome type 2A research from Erwin van Wijk and colleagues at Radboud University Medical Center in the Netherlands and RP research by Neena Haider and her team at Massachusetts Eye and Ear.
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.
Since I've spent the past few days talking in generalities, I’ll spend today’s blog giving a brief overview on the research specifically dealing with Usher syndrome.
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.
Whew! Day 4 is in the books, and what a day it was. I saw more excellent science presentations than I can count (and a few disappointing ones, too, but that’s a story for another day). I engaged in stimulating discussions about research directions throughout the day and managed to catch sight of a few Seattle landmarks while walking and talking with a colleague before hunkering down in my quaint little hotel room to write this up.
Since my return to blogging with an analysis of recent peer-reviewed literature on Usher research, another paper that will probably have relevance to a lot of our blog readers has come to my attention. In contrast to those first two papers on new Usher genes, however, this one isn’t exactly a cause for celebration.
Today was an 11-hour maelstrom* of really good science. Of all the great research stories I heard, there are several that will likely be of interest to our readers: