New gene therapy for autosomal dominant retinitis pigmentosa

The United States Food and Drug Administration (FDA) has just approved the designation of the QR-1123 therapy by the Dutch company ProQR as a new investigational drug. This drug aims to treat a form of autosomal dominant retinitis pigmentosa (RPad) caused by the P23H mutation in the rhodopsin gene (RHO).

QR-1123 is an antisense oligonucleotide, that is, a short DNA sequence designed to specifically bind to a target DNA or RNA fragment. The QR-1123 therapy aims to specifically recognize the mutated messenger RNA (mRNA) of the RHO gene and inactivate it by the action of the enzyme RNase H. This strategy called “allele-specific knockdown” only inhibits the expression of the mutated allele, the normal (non-mutated) RNA is not affected. Then, this non-mutated mRNA form dictates the synthesis of the functional RHO protein using the cellular machinery.

P23H (p.Pro23His) is the most frequent mutation of RHO causing an autosomal dominant form of retinitis pigmentosa, and QR-1123 the first drug investigated to treat this type of retinal dystrophy.

ProQR, the company promoting this therapy, plans to start a first phase 1/2 clinical trial with 12 patients later this year. This study will evaluate the safety, tolerability and dosage of the therapy, as well as its effectiveness in improving visual function. The administration of QR-1123 will be carried out by intravitreal injection.