TY - JOUR
T1 - Therapeutic options for mucopolysaccharidosis ii (Hunter disease)
AU - Kubaski, Francyne
AU - Vairo, Filippo
AU - Baldo, Guilherme
AU - Poswar, Fabiano de Oliveira
AU - Corte, Amauri Dalla
AU - Giugliani, Roberto
N1 - Funding Information:
FK and FP conducted this work during scholarship financed by CAPES - raBzil. BGndaGRreaecirpients f o NCPq - raBzil er-search scholarships. The authors acknowledge the support of FIPE-GPPG-HCPA (Grant #17-0664).
Funding Information:
FK and FP conducted this work during scholarship financed by CAPES-Brazil. GB and RG are recipients of CNPq-Brazil research scholarships. The authors acknowledge the support of FIPEGPPG-HCPA (Grant #17-0664).
Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Enzyme replacement therapy
KW - Gene therapy
KW - Glycosaminoglycans
KW - Hematopoietic stem cell transplantation
KW - Hunter syndrome
KW - Iduronate-2-sulfatase
KW - Mucopolysaccharidosis
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U2 - 10.2174/1381612826666200724161504
DO - 10.2174/1381612826666200724161504
M3 - Article
C2 - 33138761
AN - SCOPUS:85096308146
VL - 26
SP - 5100
EP - 5109
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
SN - 1381-6128
IS - 40
ER -