Proof-of-concept study for oral synthetic 9 cis-retinyl provides visual rescue for late-onset autosomal dominant retinitis pigmentosa (adRP)

A collaborative research group with scientists working in Ireland, France, USA and Canada has reported the effects of single 7-day oral retinoid supplementation lasting “at least 6 months, possibly giving visual benefit throughout remaining life in patients with advanced disease”.  The research team, led by the Institute of Genetics, University of Dublin, Trinity College, and the Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, have published the results of a Phase 1b clinical study in 5 patients with advanced late-onset retinitis pigmentosa.  The current study showed improvements over longer periods lasting over 6–12 months, suggesting “a possible reflection of the time taken for regeneration of outer segments in remaining photoreceptors in these patients”.  The authors believe that the research was the first time a visual rescue following oral 9-cis- retinyl ester administration.


In the study, patients (with advanced disease, aged 41–68 years) received seven doses of 40 mg/m2 per day of QLT091001 (Retinagenix), 9-cis-retinyl acetate, a late-stage synthetic retinoid replacement therapy administered for inherited retinal diseases. The synthetic compound was designed to replace the normal functioning of 11-cis retinal.  The QLT091001 compound is understood to convert in the body to 9-cis retinal to combine with opsin forming iso-rhodopsin and initiating the phototransduction cascade upon activation by light. The compound is a prodrug converted by hydrolysis in vivo to 9-cis-retinol, then converted to 9-cis-retinal, and thereby restoring the key biochemical component of the retinoid cycle.


In the reported study results, treatment for 7 days with oral QLT091001 showed significant improvements in Goldmann visual fields from baseline ranging from 70% to 200% in three of five subjects aged 67–68 years, with largest improvements at 7–10 months. In addition, in two GVF non-responders, one had significant visual acuity improvement (5–15 letters) from baseline after 6 months.  Further, self-reported improvements in daily living activities appeared to support the clinical findings, “including to walk without their cane, dark adaptation and improved vision in low-light environments”.  Commenting on their report, published in the BMJ Open Ophthalmology (2020;5: e000462), the authors stated that: “It is remarkable that after 62 years of retinal disease, it appears possible to re-activate dormant photoreceptors with a simple oral retinoid. The biology behind this relative delay in our study is not yet known, but we speculate that it takes longer to re-grow an adequate outer segment in our older patients”.