Current approaches and future prospects in the treatment of Hunter syndrome

Abstract

Introduction: Hunter syndrome (mucopolysaccharidosis type II) is a lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase, leading to accumulation of glycosaminoglycans. It has an X-linked recessive inheritance and its symptoms are intellectual disability, macrocephaly, dysostosis multiplex, coarse facial features, hepatosplenomegaly and others. Materials and Methods: Literature was accessed through PubMed using the keywords: Hunter syn­drome; treatment; mucopolysaccharidosis. The articles used in this review are all written after the year 2015 and have been published in peer-reviewed journals. Results: Although there is no cure for Hunter syndrome, current treatments include enzyme replace­ment therapy (ERT) with recombinant Idursulfase (IDS, Elaprase) and hematopoietic stem cell trans­plantation (HSCT). ERT reduces GAG levels in urine and plasma, improves organ function, and pro­longs a patient`s life. Its main disadvantages are an inability to cross the Blood-Brain Barrier (BBB) and reach the CNS following intravenous delivery, limiting the potential applicability to treat neuro­logical symptoms, and high incidence of development of anti-IDS antibodies. HSCT has proved to be similar to ERT in terms of reduction of GAG levels. Intrathecal administration of iduronate-2-sulfa­tase for delivery to the CNS is currently in phase II trials. Results show it is suitable for treating the neurological manifestations associated with Hunter syndrome. One of the newest treatments is gene therapy - delivery of vectors to the CNS using adeno-associated virus vectors encoding IDS (AAV9- Ids) to the cerebrospinal fluid. AAV9-Ids-treated MPSII mice showed normalization of behavioural deficits and prolonged survival. Another method, currently being investigated is polymer-nanopar­ticles which are modified with a 7-amino acid glycopeptide with an ability to deliver low molecular weight molecules - IDS across the BBB. Conclusion: Hunter syndrome is currently treated by enzyme replacement therapy and stem cell transplantation, while intrathecal ERT, gene therapy, and targeted nanoparticles are the future of the treatment of Hunter syndrome.