The safety and efficacy of gene therapy treatment for monogenic retinal and optic nerve diseases: A systematic review

Victorian evolution of inherited retinal diseases natural history registry (VENTURE study): Rationale, methodology and initial participant characteristics

“…The next most‐common clinical diagnoses of VENTURE registrants are Bietti crystalline dystrophy (7%), choroideremia (5%), Stargardt disease (5%) and cone‐rod dystrophy (5%). Compared to the distribution of IRDs in the general Australian population previously reported by the AIRDR, 38 the phenotypic distribution of VENTURE varies, representing active research interests in IRDs for which treatments are being developed 12,36 . Probable causative variants in the current VENTURE cohort were most commonly found in RPGR , CYP4V2 , USH2A, CHM and ABCA4 genes, all of which are being evaluated in gene therapy clinical trials 12 …”

“…The most common IRD is rod‐cone dystrophy (including Usher syndrome), representing 63% of all registered participants. Other common panretinal pigmentary retinopathies in VENTURE are Bietti crystalline dystrophy (7%, n = 10) and choroideremia (5%, n = 7), representing active research priorities in these conditions 12,36 . Thirteen percent of registered participants have macular dystrophies, predominantly Stargardt disease or generalised macular dystrophy (9% of all registrants, n = 14).…”

“…VENTURE participants are recruited through referrals from health practitioners (e.g., ophthalmologists, optometrists, genetic counsellors), as well as those who contact the study investigators directly wishing to be involved in research. When VENTURE commenced participant recruitment, many referrals were for IRDs that were being targeted in pre‐clinical and clinical trials assessing retinal gene therapy and other pharmaceutical and biotech interventions (e.g., gene therapy products targeting RPGR and CHM genes), 12 to ensure that those participants have access to emerging treatments. Thus, the current phenotype distribution of the study cohort has a higher representation of IRDs with active research interests, rather than being representative of the population frequency of IRDs in Australia.…”

“…VENTURE collects genotype and phenotype data across a range of IRDs to better understand each condition. Following baseline examination and confirmation of diagnosis, VENTURE participants are then enrolled into disease‐specific, prospective longitudinal cohort sub‐studies to better characterise IRDs that are being targeted in the development of new pharmaceutical and biotech interventions 12 …”

AMD Genomics: Non-Coding RNAs as Biomarkers and Therapeutic Targets

“…In terms of specific targeting to ophthalmic tissue, ncRNA therapeutics have two potential avenues, both which have demonstrated high levels of success in prior studies. Owing to the unique anatomic compartmentalization of the eye, targeting the subretinal space via surgical procedures is indeed possible as demonstrated by prior and ongoing ocular gene therapy trials [ 181 ]. Additionally, trials in cardiovascular medicine have demonstrated the ability to target specific tissue, such as the liver, through modification of surface lipid nanoparticular delivery vectors delivered systemically [ 182 , 183 ].…”