Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)

ABSTRACT

Introduction: Mucopolysaccharidosis Type II (MPS II; Hunter syndrome) is an X- linked lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS). IDS deficiency leads to primary accumulation of dermatan sulfate (DS) and heparan sulfate (HS). MPS II is both multi-systemic and progressive. Phenotypes are classified as either attenuated or severe (based on absence or presence of central nervous system impairment, respectively).

Areas covered: Current treatments available are intravenous enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), anti-inflammatory treatment, and palliative care with symptomatic surgeries. Clinical trials are being conducted for intrathecal ERT and gene therapy is under pre-clinical investigation. Treatment approaches differ based on age, clinical severity, prognosis, availability and feasibility of therapy, and health insurance. This review provides a historical account of MPS II treatment as well as treatment development with insights into benefits and/or limitations of each specific treatment.

Expert opinion: Conventional ERT and HSCT coupled with surgical intervention and palliative therapy are currently the treatment options available to MPS II patients. Intrathecal ERT and gene therapy are currently under investigation as future therapies. These investigative treatments are critical to address the limitations in treatment of the central nervous system (CNS).

KEYWORDS:

• MPS II
• enzyme replacement therapy
• hematopoietic stem cell transplantation
• gene therapy
• anti-inflammatory therapy

Article highlights

• MPS II is an X-linked recessive disorder manifesting in multi-systemic manifestations present in the CNS, skeletal, and somatic systems.

• Current treatments include conventional ERT and HSCT coupled with palliative care.

• Current treatments are limited in their efficacy on CNS impairment which decreases a patient`s quality of life.

• Intrathecal ERT is currently under clinical investigation and has shown evidence of some efficacy in the CNS although serious side effects related to the indwelling device are reported.

• Gene therapy is expected to provide self-sustaining IDS levels with an evidence of reversal of disease manifestations in mouse models

• Any treatment proposed will increase in efficacy if administered to patients before clinical symptoms of the disease are present, suggesting importance of newborn screening

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Additional information

Funding

This work was supported by the Japanese MPS Society. R Mason and S Tomatsu were supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of NIH under grant number P30GM114736. S Tomatsu was supported by National Institutes of Health grant 1R01HD065767. F Kubaski was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, from Brazil (CNPq) and INAGEMP.