Usher syndrome is an inherited retinal degeneration that affects hearing, balance, and vision. Usher syndrome caused by USH2A mutations is one of the most common causes of retinitis pigmentosa (RP) with syndromic features. Currently there is no treatment for the sensory deficits caused by Usher syndrome.
In an attempt to fill this void, QR-421a is an antisense oligonucleotide (ASO) and designed to specifically target mutations in exon 13 of the USH2A gene for the treatment of patients with RP. QR 421a binds to a specific sequence in the USH2A pre-messenger ribonucleic acid (mRNA) and modulates splicing by enhancing exon-skipping. Skipping of exon 13 from the USH2A pre-mRNA results in mRNA without exon 13, that is expected to lead to functional (albeit shorter) Usherin protein, according to ProQR.
It is hypothesized that treatment with QR-421a will result in restoration of functional Usherin protein in photoreceptors and restoration of vision.
The first-in-human study of QR-421a (PQ-421a-001) has already commenced and will evaluate the safety and tolerability of a single dose of QR-421a in adult subjects with RP due to mutations in exon 13 of the USH2A gene. QR-421a will be administered via intravitreal injection in the worst eye. A potential dose response relationship and duration of effect following a single dose of QR-421a, based on improvements in retinal structure or visual function, will also be investigated to inform selection of dose level(s) and dosing intervals for subsequent studies of QR-421a clinical development.