Stargardt disease: clinical studies over the past 5 years—a systematic review
TL;DR
Although STGD1 remains a challenging condition, new therapies in this review have shown potential in clinical trials, even though challenges such as off-target effects and DNA repair errors remain.
Abstract
Stargardt disease type 1 (STGD1) is the most common juvenile macular degeneration and one of the leading causes of visual impairment and blindness among children and working adults across Europe. There are currently no approved therapies for STGD1, but several therapeutic approaches including pharmacotherapy, gene therapy, neuroprotection, and stem cell therapy are under investigation in clinical studies and trials. Here, we review the current status of evolving therapies for STDG1. This systematic review is based on the PRISMA‑P checklist using various scientific databases. Only case series and (non-)randomized clinical studies were included, with preclinical and basic science studies excluded. All included studies were individually assessed using the ROBINS‑I Tool of the Cochrane Collaboration and the TREND-Checklist for BIAS assessment. From the initial search, 314 records were identified, including 72 from PubMed, 96 from Embase, 41 from the Cochrane Library, 68 from Google Scholar, and 37 from Epistemonikos. After removing duplicates, the titles, abstracts, and full texts were screened according to predefined PICO criteria: population with genetically and clinically confirmed STDG1, interventions such as gene therapy, pharmacological approaches, stem cell therapy, and neuroprotection; comparison groups appropriate to the study design, such as placebo, the fellow eye, natural progression, or historical cohorts; and outcomes, including structural progression (assessed by fundus autofluorescence and optical coherence tomography), functional outcomes, and safety. Six studies met these criteria and were included. Of these, one investigated the gene therapy SAR422459, one evaluated the pharmacological agent emixustat, three assessed stem cell-based retinal pigment epithelium transplantation, and one examined neuroprotection through saffron supplementation. Although STGD1 remains a challenging condition, new therapies in this review have shown potential in clinical trials. Ongoing methods aim to optimize the use of stem cell-based retinal pigment epithelium cells, refine delivery methods for the large ABCA4 gene, and explore genome editing techniques, such as CRISPR, to correct ABCA4 mutations, even though challenges such as off-target effects and DNA repair errors remain. Pharmacological approaches are focused on optimizing dosing for safety and efficacy. With further research on larger cohorts and long-term evaluation, there is hope for effective therapies.
