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Developing RNA Medicines for Rare Genetic Diseases

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There are approximately 7,000 known rare diseases, however, less than 6% of these have a treatment. It is estimated that between 25–35 million Americans live with a rare disease. The company ProQR is dedicated to developing new therapeutics for patients living with untreated rare diseases.

We caught up with Daniel de Boer, Chief Executive Officer at ProQR to learn more about the company’s approach to finding new treatments for rare genetic diseases. Daniel discusses the interim results from their study on the use of QR-110 in patients with a specific type of Leber congenital amaurosis – a condition that is the most common cause of inherited loss of vision in children. He also touches on some of the other investigational drugs currently in development and describes the indications they being investigated for.

Q: Could you tell us more about ProQR, the company history, mission and goals?

At ProQR we develop RNA medicines for rare genetic diseases. I started ProQR in 2012 because my son was diagnosed with a rare genetic disease for which there was no treatment. We now have a diversified pipeline of programs for severe genetic eye and skin disorders with the goal to have a positive impact on the lives of patients and their loved ones.

ProQR recently announced results from a planned interim analysis of its Phase 1/2 trial of QR-110 in patients with Leber congenital amaurosis 10.

Q: What is Leber’s congenital amaurosis 10?

Leber congenital amaurosis (LCA) is the most common genetic cause of blindness in children. LCA10 is a one of the most severe forms that causes blindness very early in life. LCA10 is caused by mutations in the CEP290 gene. We believe there are at least 2,000 patients in the Western world that have LCA10 caused specifically by the p.Cys998X mutation, which ProQR is currently therapeutically targeting using QR-110, an investigational medicine.

Because of this mutation the light sensitive cells in the retina (photoreceptor cells) cannot perform their function which leads to involuntary eye movement and impaired vision. There are currently no approved therapies for LCA10.

Q: What is QR-110 and what were the key findings of the study?

QR-110 is an investigational RNA medicine that is designed to address the underlying cause of LCA10 by correcting the p.Cys998X mutation in the CEP290 mRNA. By correcting the mutation a “normal” (wild-type) mRNA is formed that can be used to create a functional CEP290 protein. In an interim analysis of the ongoing Phase 1/2 clinical study of QR-110 in LCA10 patients we observed rapid and sustained improvements in vision in the majority of patients. We believe the findings are clinically meaningful and very encouraging for the program and the LCA10 community.

Q: Could you provide an update on the therapeutic development of this lead molecule?

Based on the positive interim results of the Phase 1/2 clinical trial we decided to stop enrolment and are now planning a pivotal Phase 2/3 study that could serve as the sole registration trial for QR-110. We plan to start this 12-month study during the first half of 2019.

Q: What other drug candidates are currently in development and what indications are they being investigated for?

We have a broad pipeline of RNA medicines targeting severe genetic rare diseases. Besides QR-110 for LCA10 we are developing several other programs for genetic eye disorders including Usher syndrome, Stargardt’s disease and Fuchs endothelial corneal dystrophy.

Usher syndrome is the leading cause of combined deafness and blindness – there is currently no treatment for the vision loss associated with the disease. Our first Usher program using the novel investigational drug QR-421a, targets mutations in exon 13 of the USH2A gene. QR-421a will enter clinical development towards the end of 2018.

We have recently started the first clinical trial of QR-313 in patients with dystrophic epidermolysis bullosa (DEB). DEB is a terrible skin disease, sometimes referred to as the “butterfly disease” since patients have skin that is as fragile as the wings of a butterfly. Symptoms include poorly healing wounds, skin infection, fusion of fingers and toes, and a high risk of developing an aggressive form of skin cancer.

Daniel de Boer was speaking to Laura Elizabeth Mason, Science Writer for Technology Networks.