Mucopolysaccharidosis Type IIIA, Mucopolysaccharidosis Type IIIB
Conditions
Keywords
Mucopolysaccharidosis, MPS, Sanfilippo
Brief summary
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
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: 1. Individual rates of decline in motor and cognitive function in a cohort of potential clinical trial patients 2. The natural history of outcome measures in order to assess their appropriateness as outcomes in an eventual trial 3. Baseline functional data in patients who will be potential candidates for an eventual trial 4. 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.
Interventions
PROCEDURELumbar puncture
Sponsors
Sanfilippo Children's Research Foundation
The Sanfilippo Research Foundation
The Children's Medical Research Foundation
Nationwide Children's Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 2 years old or greater 2. Confirmed diagnosis of MPSIIIA or MPSIIIB by either of two methods: 1. No detectable or significantly reduced NAGLU (MPSIIIB) or SGSH (MPSIIIA) activity in serum or leukocyte assay 2. Genomic DNA mutation analysis demonstrating a homozygous or compound heterozygous mutations in the NAGLU (MPSIIIB) or SGSH (MPSIIIA) genes 3. Clinical history of or examination features of neurologic dysfunction.
Exclusion criteria
1. Inability to participate in the clinical evaluations 2. Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics 3. Inability to be safely sedated in the opinion of the clinical anesthesiologist
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive function | up to 12 months | Assessed using the Leiter International Performance assessment, a non-verbal assessment of cognitive function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adaptive functioning | Months 0, 6, and 12 | Parental assessment of adaptive functioning using the Adaptive Behavioral Assessment System |
| Emotional/behavioral function | Months 0, 6, and 12 | Assessment of emotional/behavioral problems using the Child Behavioral Checklist |
| White and grey matter brain volumes | Months 0 and 12 | Assessment of brain volumes by MRI. MRI will be performed under sedation. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum and cerebrospinal fluid NAGLU (MPSIIIB subjects) or SGSH (MPSIIIA subjects) levels | Months 0 and 12 | Measurement of NAGLU or SGSH activity in serum (by venipuncture) and CSF (by lumbar puncture). Lumbar puncture will be performed under sedation. |
| Liver size | Months 0 and 12 | Liver volume will be assessed by abdominal MRI obtained under the same sedation event as brain MRI and lumbar puncture. |
Countries
United States
Outcome results
None listed