Abstract
In mucopolysaccharidoses (MPS), glycosaminoglycans (GAG) accumulate in tissues. In MPS II, approximately two-thirds of patients are cognitively impaired. We investigated levels of GAG in cerebrospinal fluid (CSF) in different populations from four clinical studies (including NCT00920647 and NCT01449240). Data indicate that MPS II patients with cognitive impairment have elevated levels of CSF GAG, whereas those with the attenuated phenotype typically have levels falling between those of the cognitively affected patients and healthy controls.
Highlights
Mucopolysaccharidosis II (MPS II; Hunter syndrome) is an X-linked lysosomal storage disorder (LSD) caused by a deficiency in the enzyme iduronate-2-sulfatase (EC 3.1.6.13), leading to the accumulation of glycosaminoglycans (GAGs) in lysosomes [1]
Our study expands on this and on the Hendriksz et al study that reported differences between pediatric and adult MPS II patients' cerebrospinal fluid (CSF) GAG levels [16]. This is the first study to undertake a systematic exploration of CSF GAG levels in MPS II patients and to compare them to healthy individuals
Our data show that healthy adults or surrogate-normal children have CSF GAG levels that are, on average, 50–70 ng/mL, depending on age, and almost always below 200 ng/mL
Summary
Mucopolysaccharidosis II (MPS II; Hunter syndrome) is an X-linked lysosomal storage disorder (LSD) caused by a deficiency in the enzyme iduronate-2-sulfatase (EC 3.1.6.13), leading to the accumulation of glycosaminoglycans (GAGs) in lysosomes [1]. All patients with MPS II experience a variety of somatic signs and symptoms associated with significant morbidity and early mortality [5,6]. Idursulfase (Elaprase®, Shire, Lexington, MA, USA), a recombinant human iduronate-2-sulfatase, has been approved as an intravenous (IV) medicinal product for the treatment of MPS II since 2006 in the United States and 2007 in Europe [8]. Intravenous idursulfase does not cross the blood–brain barrier at the therapeutic dose and is not expected to alter the cognitive decline seen in the severe phenotype [9]
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