Key challenges in developing a gene therapy for Usher syndrome: machine-assisted scoping review

Despite compelling empirical evidence demonstrating its efficacy, gene therapies for usher syndrome (USH) are not yet available for the patient's usage. This scoping review assessed the current scenario and analysed the challenges in implementing gene therapies for USH. A literature search was conducted using PubMed and Google Scholar through an artificial intelligence (AI) tool, MaiA, focusing on relevant publications from the last 10 years. We followed the methodological guidance of the Joanna Briggs Institute (JBI) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) checklist. Of 517 records, 51 reports were considered for final analysis. It identified and categorized challenges across four key areas: preclinical, clinical, economic, and regulatory. Of all, many reports (30) highlighted the preclinical challenges where the USH gene development process encountered roadblocks. Specifically, preclinical challenges included the lack of suitable in-vivo models and effective delivery methods. Clinical challenges focused on establishing clear endpoints and long-term safety and efficacy. Economic challenges addressed diagnostic issues and manufacturing hurdles, while regulatory challenges focused on expedited evaluation processes and guidance for clinical development. Our analysis uncovered key barriers to clinical translation of USH gene therapy and strategies to address them. Researchers are employing innovative approaches, including novel delivery methods such as minigenes and nanoparticles, inventive clinical trial designs, cohesive regulatory frameworks, strategic market assessments, and collaborative research initiatives. These efforts hold promise for impactful disease-cure and modifying interventions ultimately enhancing the quality of life for USH patients.