Cognitive and imaging data are sensitive markers that can be used to assess changes in the disease course of Sanfilippo syndrome type B and evaluate new therapies, according to researchers.
Their study, “Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B,” was published in the Journal of Pediatrics.
There is a need for a better understanding of the clinical progression of mucopolysaccharidosis (MPS) type IIIB (MPS IIIB, or Sanfilippo syndrome type B) to identify disease stages and assess potential treatments, especially because early studies of an enzyme replacement therapy and a gene therapy have generated encouraging results.
Researchers conducted a prospective, multicenter study (NCT01509768), referred to as the MPS IIIB natural history study, to evaluate the natural course of disease progression in children with Sanfilippo syndrome type B.
Nineteen patients ages 1-10 were enrolled in the study. They had been diagnosed with Sanfilippo type B based on a gene mutation or enzyme deficiency analysis.
The children underwent detailed assessments that involved clinical, developmental, imaging (using brain magnetic resonance imaging, or MRI) and biochemical aspects at the start of the study and then at six and 12-month intervals.
Their neurodevelopment and quality of life were assessed using standard tests, such as Bayley Scales of Infant Development, Third Edition (BSID-III), and Infant Toddler Quality of Life (ITQOL).
The results showed that cognition, behavior, and brain cortical gray matter volume (GMV) decreased over the 12-month period. The developmental quotient (DQ) — which measures a child’s behavioral growth to maturity — was lower in patients diagnosed after age 6 compared to those diagnosed before that.
Regarding GMV, most children diagnosed before age 6 showed a consistent decrease, whereas those diagnosed after age 6 did not show a great variability.
Biochemical tests indicated that urine glycosaminoglycans (GAG) and cerebrospinal fluid heparan sulphate levels, both of which are established as markers of Sanfilippo syndrome type B, were higher than normal across all age groups.
These results suggest that “neuro-cognitive and adaptive function, and quantitative MRI are appropriate methods to evaluate patients in future efficacy trials for MPS IIIB treatments,” because these were shown to sensitively track deterioration in patients younger than 8.6, researchers wrote.
They pointed out, however, that although biomarkers may have prognostic value, additional research into the use of these markers to track disease severity is needed.