Natural History Studies of Mucopolysaccharidosis III

Nationwide Children's Hospital

Status: Completed

Conditions: Mucopolysaccharidosis Type IIIB; Mucopolysaccharidosis Type IIIA

Treatments: Device: Magnetic Resonance Imaging (MRI) of the brain; Procedure: Lumbar puncture

Study type: Observational

Funder types: Other

Identifiers

NCT02037880

MPSIII-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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

Trial design

25 participants in 1 patient group

MPS IIIA/B Subjects

Description:

Cohort will be followed for one year to assess natural history of the disease.

Treatment:

Device: Magnetic Resonance Imaging (MRI) of the brain

Procedure: Lumbar puncture