Collection and Study of Cerebrospinal Fluid in Patients With Hunter Syndrome

The purpose of the study is to collect data on CSF biomarkers in patients with Hunter Syndrome that would serve as reference data for comparison with cognitively impaired patients with Hunter syndrome, patients with other lysosomal storage diseases, or other diseases with CNS involvement.

To determine levels of glycosaminoglycans (GAGs), including dermatan sulfate (DS) and heparan sulfate (HS), GAG-degradation products, and other biomarkers of central nervous system (CNS) and lysosomal function in cerebrospinal fluid (CSF) in pediatric and adult patients with Hunter syndrome.

The study population will consist of pediatric (<18 years of age) and adult (≥18 years of age) male patients with Hunter syndrome. Up to approximately 60 patients (approximately 30 adults and 30 children) may be enrolled in this study.

• Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. Epub 2007 Nov 23. Review.
• Dickson PI. Novel treatments and future perspectives: outcomes of intrathecal drug delivery. Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S124-7. Review.
• Dickson P, McEntee M, Vogler C, Le S, Levy B, Peinovich M, Hanson S, Passage M, Kakkis E. Intrathecal enzyme replacement therapy: successful treatment of brain disease via the cerebrospinal fluid. Mol Genet Metab. 2007 May;91(1):61-8. Epub 2007 Feb 26.

Inclusion Criteria:

• The patient is male and has a documented diagnosis of Hunter syndrome (MPSII).
• The adult patient has completed a cognitive assessment at screening/baseline or within the previous 3 months and has been determined to have an intelligence quotient (IQ) ≥78. Note: cognitive evaluation of pediatric patients is not required.
• The adult patient or the adult patient's legally authorized representative(s) has voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed.
• The pediatric patient must be scheduled to undergo a non-study related lumbar puncture or other medical or diagnostic procedure that requires the administration of general anesthesia. The pediatric patient's parent(s) or legally authorized representative(s) must have provided written informed consent (with patient assent as relevant), after all relevant aspects of the study have been explained and discussed, to allow CSF sample collection for this study in conjunction with performance of the non-study related procedure requiring general anesthesia.

Exclusion Criteria:

• The patient has a history of complications from a previous lumbar puncture(s) or technical challenges in conducting lumbar puncture.
• The patient has received a hematopoietic stem cell transplant.
• The patient has taken aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or other over-the-counter or prescription medications that could affect blood clot formation within the 7 days prior to lumbar puncture, or has ingested such medications within 7 days prior to any study-related procedure in which a change in potential blood clot formation would be deleterious.
• The patient is currently receiving treatment with intrathecal idursulfase-IT.
• The patient is currently enrolled in an interventional clinical trial.
• The patient has participated in a clinical trial of any investigational drug, including idursulfase-IT, or device within the 30 days prior to study entry.