Natural History Studies of Mucopolysaccharidosis III

Study Overview
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Brief Summary
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The purpose of this study is to assess rates of decline in motor and cognitive functional measures, and to assess potential biomarkers, in order to identify potential outcome measure appropriate for use in therapeutic clinical trials.

Detailed Description
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Mucopolysaccharidosis (MPS) type III (Sanfilippo syndrome) is a group of four devastating genetic diseases that result in the abnormal accumulation of glycosaminoglycans in body tissues. In MPSIII the predominant symptoms occur due to accumulation within the central nervous system (CNS), including the brain and spinal cord, resulting in cognitive decline, motor dysfunction, and eventual death. In anticipation for future therapeutic studies for MPSIIIA and MPSIIIB, we are performing a natural history study to identify the following: Individual rates of decline in motor and cognitive function in a cohort of potential clinical trial patients The natural history of outcome measures in order to assess their appropriateness as outcomes in an eventual trial Baseline functional data in patients who will be potential candidates for an eventual trial Biomarkers of disease progression over a 12-month interval, including changes in brain MRI and in cerebrospinal fluid Patients in this study will need to come to Nationwide Children's Hospital in Columbus, Ohio, three times. At each of these three time points, cognitive outcome measures will be assessed: at baseline (visit 1), 6 months (visit 2), and at 12 months (visit 3). At baseline (visit 1) and 12 months (visit 3), an MRI and a lumbar puncture will be performed.

Official Title
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Natural History Studies of Mucopolysaccharidosis III

Conditions
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Mucopolysaccharidosis Type IIIA, Mucopolysaccharidosis Type IIIB

Intervention / Treatment
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* Procedure: Lumbar puncture
* Device: Magnetic Resonance Imaging (MRI) of the brain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 2 years old or greater Confirmed diagnosis of MPSIIIA or MPSIIIB by either of two methods: No detectable or significantly reduced NAGLU (MPSIIIB) or SGSH (MPSIIIA) activity in serum or leukocyte assay Genomic DNA mutation analysis demonstrating a homozygous or compound heterozygous mutations in the NAGLU (MPSIIIB) or SGSH (MPSIIIA) genes Clinical history of or examination features of neurologic dysfunction. Exclusion Criteria: Inability to participate in the clinical evaluations Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics Inability to be safely sedated in the opinion of the clinical anesthesiologist

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MPS IIIA/B Subjects<br>Cohort will be followed for one year to assess natural history of the disease. | Procedure: Lumbar puncture<br> <br> Device: Magnetic Resonance Imaging (MRI) of the brain<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function | Assessed using the Leiter International Performance assessment, a non-verbal assessment of cognitive function. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adaptive functioning | Parental assessment of adaptive functioning using the Adaptive Behavioral Assessment System | Months 0, 6, and 12 | 
| Emotional/behavioral function | Assessment of emotional/behavioral problems using the Child Behavioral Checklist | Months 0, 6, and 12 | 
| White and grey matter brain volumes | Assessment of brain volumes by MRI. MRI will be performed under sedation. | Months 0 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mucopolysaccharidosis, MPS, Sanfilippo