Predicting intelligence in MPS IH with biomarkers

Abnormal cerebral spinal fluid (CSF) characteristics were previously reported in children with severe mucopolysaccharidosis type I (MPS IH Hurler syndrome), a progressive lysosomal storage disease associated with rapid neurocognitive decline, worsening multi-system organ dysfunction, and early death. The present objective was to evaluate whether intrathecal (IT) enzyme replacement therapy (ERT) added to intravenous ERT and hematopoietic cell transplantation (HCT) is associated with attenuation of CSF abnormalities and whether this change has clinical correlates. Twenty-four MPS IH patients received IT ERT at four time points in the peri-transplant period. At these times, CSF opening pressure (OP), heparin sulfate (HS), non-reducing ends (NRE I0S0 and I0S6), heparin cofactor II thrombin complex (HCIIT), and inflammatory markers were measured. Neurocognitive functioning (i.e., infant IQ) was quantified at baseline, 1 year after HCT, and 2 years after HCT. There were no adverse events due to the administration of IT ERT. An association between attenuated CSF biomarkers and IQ change following transplant was examined. Significant reductions in CSF abnormalities were seen between time points 1 and 2, i.e. prior to HCT, for OP, NRE I0S0 and I0S6, and HCTIIT (p=0.036, 0.001, 0.006, and 0.026, respectively), and across time points 1 through 4 for NRE I0S0 and I0S6, HS, and HCIIT (p