Lysosomal storage disorders (LSD) are a group of rare inherited metabolic disorders caused by defects in lysosomal function. Among these, Mucopolysaccharidoses (MPS) are characterized by the loss of function of lysosomal enzymes responsible for the degradation of glycosaminoglycans (GAGs). This defect leads to the production, at the cellular level, of secondary storages comprised of undegraded proteins. In some of these syndromes, this translates into a neurodegenerative phenotype with pediatric dementia. Promoting the degradation of secondary storages is one of the most promising therapeutic strategies to prevent neurodegeneration. Genetic overexpression of the transcription factor EB (TFEB), which controls genes involved in the autophagy/lysosomal degradation process, seems to promote the degradation of protein aggregates in animal models of neurodegeneration. However, there are still few synthetic drugs capable of stimulating TFEB and crossing the blood-brain barrier. In the current study, using validated animal and cellular models of MPS, we are testing a compound that has been shown to promote TFEB-mediated autophagy and lysosomal biogenesis in wild-type/control animals. Our in vitro analysis demonstrated that the drug is effective in patients' cell lines of various types of MPS, shedding light on the mechanism by which it activates autophagic flux in the context of disease. Analyses conducted in a validated animal model of MPS-IIIA have shown that the drug improves the cognitive deficits and favours the clearance of secondary storages composed of beta-amyloid. These results provide proof-of-concept evidence on a novel therapeutic compound for the treatment of LSDs.