ProQR Therapeutics announced the publication of a peer-reviewed manuscript describing the preclinical validation for the use of QR-110 in the treatment of Leber’s congenital amaurosis 10 (LCA10) in the journal Molecular Therapy – Nucleic Acids.
LCA10 is a severe inherited retinal dystrophy associated with mutations in the CEP290 gene. QR-110 is an RNA-based drug candidate that has the potential to restore sight or slow down the process of vision loss in patients with LCA10 by correcting the most common mutation causing LCA10, p.Cys998X. This mutation causes incorrect splicing of CEP290 mRNA.
This publication details the screening process by which QR-110 was identified as a potentially optimal therapeutic candidate using a patient-derived retinal organoid (“eye cup”) model. In additional in vitro testing, QR-110 demonstrated a dose-dependent restoration of mRNA and functional CEP290 protein while in vivotesting showed that QR-110 was well-tolerated following intravitreal injection. The results from this study suggest the pharmacodynamic, pharmacokinetic and safety properties make QR-110 a promising candidate for the treatment of LCA10. On the basis of the work detailed in this publication, QR-110 is currently being evaluated in a phase 1/2 clinical trial in patients with LCA10.
“Given that the p.Cys998X mutation is a uniquely human mutation, there is no reliable in vivo model. Therefore, the eye cup model was essential in our preclinical validation process described in the paper,” Peter Adamson, PhD, senior vice president of ophthalmology for ProQR, said in a company news release. “The ongoing clinical trial of QR-110 in patients with LCA10 is evaluating the predictive accuracy of the model. If successful, we intend to use the platform to move our additional ophthalmology programs towards clinical development.”