Altogether, the herein obtained results demonstrate that, following Idua suppression, Drosophila manifests key neurological and viability-related pathologies, which represent phenotypes indicative of human Hurler syndrome, thereby highlighting the strong potential of the “fly-IduaRNAi” genetic platform to serve as a reliable and effective in vivo animal disease model for mechanistically investigating Hurler syndrome pathogenesis and pre-clinically supporting high-throughput drug-screening systems, moving towards the discovery of novel therapeutic schemes and regimens. Here, IDUA is linked to glycogen storage disease VI.