About Usher syndrome type 2
What is Usher syndrome type 2?
Usher syndrome is a rare genetic disease that is the leading cause of combined deafness and blindness. Patients with Usher syndrome type 2 (USH2), the most common type of Usher syndrome, have a moderate to severe hearing impairment from birth and commonly experience the first symptoms of night blindness in their second decade of life, which progresses to complete blindness by the third or fourth decade of life. The progressive vision loss in these patients is known as retinitis pigmentosa (RP).
What causes Usher syndrome type 2?
USH2 is most commonly caused by mutations (or mistakes) in a gene in the DNA called the USH2A gene. This gene is responsible for the formation of the usherin protein. The mutation results in a lack of (functional) usherin protein and disrupts a process called photo transduction in the light detecting cells (rods and cones) in the retina causing RP.
The hearing impairment that patients can experience is often manageable with hearing aids or cochlear implants. However, there are currently no available treatment options that target the underlying cause of the vision loss associated with this disease.
ProQR is developing a novel investigational drug called QR-421a to treat RP in patients that have USH2 due to a mutation in a specific part of the USH2A gene, called exon 13. In the Western world there are approximately 16,000 patients that experience vision loss due to a mutation in exon 13 of the USH2A gene. 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. Skipping of exon 13 in the "blueprint" is expected to lead to a shortened but functional usherin protein. By restoring functional usherin protein expression, QR-421a aims to treat the underlying cause of RP associated with USH2. QR-421a is intended to be administered via intravitreal (into the eye) injections. Beyond QR-421a, we are developing QR-411, targeting the approximately 1,000 patients that have Usher syndrome due to the PE40 mutation (also known as c.7595-2144A>G) in USH2A.
QR-421a clinical trials
A first-in-human clinical trial of QR-421a is ongoing. The Phase 1/2 study, named Stellar, includes adults that experience vision loss due to mutation(s) in exon 13 of the USH2A gene. This Phase 1/2 clinical trial is designed to evaluate the safety and tolerability of QR-421a. Patient benefit will be assessed as well. Three-months interim findings from Stellar, reported in March 2020, suggested QR-421a given as a single intravitreal injection was safe and well tolerated. Two of eight participants in the treated groups responded to QR-421a treatment thus far showing benefit in multiple outcome measures. A similar response was not observed in the six participants included in the control (“sham procedure”) group. Based on these early positive findings we will continue the trial as designed at expert centers in North America and select European countries.
Information for patients
QR-421a is an experimental medicine that we are developing to treat the vision loss in patients with Usher syndrome or RP due to mutations in a specific part of the USH2A gene, called exon 13. A first clinical study, STELLAR, is ongoing. For more information about the program please visit this page since we will post regular updates here first. If you have any other questions please read the FAQ or contact us through the contact form.
Partnership with FFB
We teamed up with the Foundation Fighting Blindness (FFB) to develop QR-421a for Ushers syndrome. In the partnership the foundation supports the trial financially and provides knowledge and knowhow on the disease, including through the learnings from the “RUSH2A” natural history study FFB is conducting. Learn more about the Foundation Fighting Blindness and read our press release.
What is QR-421a?
QR-421a is an experimental medicine that is designed to treat RP associated with Usher syndrome type 2 caused by mutations in exon 13 of the USH2A gene. By restoring functional usherin protein expression, QR-421a aims to treat the underlying cause of RP associated with the disease. QR-421a has shown promising results in the laboratory and is currently being tested in humans.
When and where will QR-421a be tested?
A first clinical study, STELLAR, is ongoing. The study is planned to be conducted at expert centers in North America and selected European countries. We expect the first interim results from this study to be available in mid-2019. Updates will be posted to this website so please check back regularly.
What are known exon 13 mutations of the USH2A gene?
Different mutations cause Usher syndrome type 2. The most common mutations in exon 13 of the USH2A gene are the c.2299delG and the c.2276G>T mutation. A list of known exon 13 mutations can be found here. We recommend that you talk to your physician if you have questions regarding genetic mutations.