Eye On the Cure Research News

Dec 16, 2019

First Patient Receives ProQR’s AON Therapy in Clinical Trial for RP Caused by RHO-P23H Mutation

The trial becomes ProQR’s third human study for inherited retinal disease therapies

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ProQR, a developer of RNA therapies in the Netherlands, has announced that the first patient in its Aurora Phase 1/2 clinical trial has received QR-1123, the company’s emerging therapy for autosomal dominant retinitis pigmentosa (adRP) caused by the P23H mutation in the gene RHO. The variant is the most prevalent variant causing adRP in the US, affecting approximately 2,500 people. The study, which plans to enroll 35 participants, is taking place at the Retina Foundation of the Southwest in Dallas, Texas, and VitreoRetinal Associates in Gainesville, Florida.

RHO, also known as rhodopsin, is a protein that enables rod photoreceptors to become light sensitive. Rods are the cells in the retina that give people peripheral vision and vision in dim settings. People with RP caused by RHO mutations (including P23H) lose peripheral vision and their ability to see in the dark.  Over time they can lose central vision, as well.

The start of the QR-1123 clinical trial is a milestone advancement, because it is one of the first, if not the first, gene-targeted therapy for an autosomal dominant inherited retinal disease

Ben Yerxa, PhD, chief executive officer, Foundation Fighting Blindness

QR-1123 is comprised of antisense oligonucleotides (AONs), small pieces of genetic material designed to mask the RHO-P23H mutation in RNA, the genetic messages that cells read to make proteins. The P23H mutation causes a toxic RHO protein to be expressed. In lab studies, QR-1123 masked the P23H mutation so that functional protein was made. QR-1123 is delivered by injection into the vitreous, the soft gel in the middle of the eye.

“The start of the QR-1123 clinical trial is a milestone advancement, because it is one of the first, if not the first, gene-targeted therapy for an autosomal dominant inherited retinal disease,” explains Ben Yerxa, PhD, chief executive officer at Foundation Fighting Blindness. “Dominant conditions can be challenging to treat, because the toxic protein must be knocked down while ensuring that functional protein is made. In recessive disease, there normally is no toxic protein to be shut down, so we only need to produce the functional protein.”

QR-1123 becomes ProQR’s third clinical program for an inherited retinal disease (IRD). The company’s other clinical programs are QR-110 for LCA 10 caused by the p.Cys998X mutation in the CEP290 gene and QR-421a for Usher syndrome type 2A caused by mutations in exon 13 of the USH2A gene. The Foundation Fighting Blindness is investing up to $7.5 million in the development of QR-421a through its RD Fund, a venture philanthropy fund for emerging therapies in early or planned clinical trials.