In vivo-In vitro trials in Developing for therapeuticstrategies of Stargardt disease with desirable future

Stargardt disease (STGD۱) is a common childhood inherited retinal disease(IRDs), which is caused by defects in the ABCA۴ gene, a subgroup of ABCsuperfamily(ATP- binding cassette) called transporter proteins. Theaccumulation of Lipofuscin, N-retinylidene-N-retinylethanolamineproducts(A۲E), due to a biallelic mutation in ABCA۴(abca۴-/-) leading toretinal. Pigment epithelial (RPE) atrophy following effects on photoreceptorcells. The patients have problems in central visual with diagnostic signs infundus autofluorescence (FAF) imaging into retinal fleck lesions.A comparison of several strategies in therapeutic for Stargardt disease donesome of which, including, molecular therapies (pharmacological inhibitorssuch as RPE۶۵ inhibitors, RBP۴(retinol-binding protein ۴), Fenretinide,Emixustat, Aldehyde traps like primary amine-containing drugs, Deuteratedform of vitamin A like C۲۰-D۳-retinyl acetate) that reduce bisretinoidproducts(N-retinylidene-N-retinylethanolamin), all-trans retinaldehyde, andaccumulation of lipofuscin. Also gene therapy with viral vectors (Lentiviralvector with the largest capacity, Adeno-associated viral vector) andultimately CRISPR techniques, specifically Base editing, indeed have beenexperimented. The molecular therapies are yet in pre-clinical phases ۲ and ۳.Gene therapy with viral vectors is effective in both in vivo and invitro. TheCRISPR-Cas۹ way is being developed and needs attempts for betterresponses to treatment of STGD۱. AAV-dual vector (۵' and ۳' ABCA۴transgene) with no pathogenesis for the host and base-editing is also a viablestrategy, both can be useful and more desirable in the future of Stargardtdisease.

کلیدواژه ها:

Stargardt ، lipofuscin ، bisretinoids ، pharmacological ، deuterated ، AAV vector ، base-editing ، CRISPR-Cas۹