Francyne Kubaski, Filippo Vairo, Guilherme Baldo, Fabiano de Oliveira Poswar, Amauri Dalla Corte and Roberto Giugliani* Pages 5100 - 5109 ( 10 )
Background: Mucopolysaccharidosis type II (Hunter syndrome, or MPS II) is an X-linked lysosomal disorder caused by the deficiency of iduronate-2-sulfatase, which leads to the accumulation of glycosaminoglycans (GAGs) in a variety of tissues, resulting in a multisystemic disease that can also impair the central nervous system (CNS).
Objective: This review focuses on providing the latest information and expert opinion about the therapies available and under development for MPS II.
Methods: We have comprehensively revised the latest studies about hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy (ERT - intravenous, intrathecal, intracerebroventricular, and intravenous with fusion proteins), small molecules, gene therapy/genome editing, and supportive management.
Results and Discussion: Intravenous ERT is a well-established specific therapy, which ameliorates the somatic features but not the CNS manifestations. Intrathecal or intracerebroventricular ERT and intravenous ERT with fusion proteins, presently under development, seem to be able to reduce the levels of GAGs in the CNS and have the potential of reducing the impact of the neurological burden of the disease. Gene therapy and/or genome editing have shown promising results in preclinical studies, bringing hope for a “one-time therapy” soon. Results with HSCT in MPS II are controversial, and small molecules could potentially address some disease manifestations. In addition to the specific therapeutic options, supportive care plays a major role in the management of these patients.
Conclusion: At this time, the treatment of individuals with MPS II is mainly based on intravenous ERT, whereas HSCT can be a potential alternative in specific cases. In the coming years, several new therapy options that target the neurological phenotype of MPS II should be available.
Mucopolysaccharidosis, Hunter syndrome, iduronate-2-sulfatase, glycosaminoglycans, enzyme replacement therapy, gene therapy, hematopoietic stem cell transplantation.
Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, Postgraduation Program in Medicine: Medical Sciences, UFRGS, Porto Alegre, Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre