The potential of gene therapy for mucopolysaccharidosis type I

ABSTRACT Introduction: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, characterized by deficient IDUA enzyme production and storage of glycosaminoglycans in tissues. Currently, therapeutic strategies approved have shown an improvement in quality of life of patients, but the majority of severe symptoms including cognitive and skeletal alterations persist. Gene therapy aimed to correct the genetic defect holds promise. Indeed, preclinical results show that it may be possible to develop a gene therapy strategy that may overcome the present limitations. In this review, authors review studies involving gene therapy for MPS I in the last years and highlight the most promising approaches. Areas covered: Authors review main studies involving gene therapy and genome editing for MPS I in the last 2–3 decades, from the initial in vitro studies up to the first clinical trials, and prospect what the future may hold for this technology in this disease. Expert opinion: Among all strategies studied, viral gene therapy and genome editing are being applied in clinical trials. Some of the results are inconclusive while scaling the process from animal models to human. The key for better outcomes relies on giving patients a proper therapy.