A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise

Med Res Arch. 2020 Feb 1;8(2):10.18103/mra.v8i2.2045. doi: 10.18103/mra.v8i2.2045. Epub 2020 Feb 21.


Mucopolysaccharidoses III (MPS III, Sanfilippo syndrome) is a subtype of the Mucopolysaccharidoses (MPS), a group of inherited lysosomal disorders caused by a deficiency of lysosomal enzymes responsible for catabolizing glycosaminoglycans (GAGs). Although MPS III is rare, MPS diseases as a group are relatively frequent with an overall incidence of approximately 1 in 20,000 - 25,000 births. MPS III are paediatric diseases, which cause learning difficulties, behavioural disorders and dementia, as well as skeletal deformities and ultimately result in premature death. There are currently no approved treatments for MPS III, but a number of therapeutic approaches are under development. In the past 30 years, research using cellular and animal models have led to clinical trials involving enzyme replacement therapy (ERT), substrate reduction therapy (SRT) and gene therapy, while stem cells approaches remain at the pre-clinical stage. Although safety and clinical efficacy in animal models have shown promise, the results of clinical trials have proved costly and shown limited therapeutic effects. In this review, we describe the most recent results from clinical trials. While ERT and gene therapy are the most developed therapies for MPS III, we highlight the work that needs to be done to bring us closer to a real treatment for these devastating diseases.

Keywords: Mucopolysaccharidoses III; Sanfilippo syndrome; clinical trial; enzyme replacement therapy; gene therapy; lysosomal storage disease; neurodegeneration; stem cell therapy; substrate reduction therapy.