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
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.