Quantitative in vivo brain magnetic resonance spectroscopic monitoring of neurological involvement in mucopolysaccharidosis type II (Hunter Syndrome)
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Neurological involvement in X-linked mucopolysaccharidosis type II (Hunter syndrome) is indicative of more severe disease, but is not attenuated by current enzyme replacement therapy which does not significantly penetrate the blood–brain barrier. Magnetic resonance spectroscopy is an objective method of determining brain metabolites and has the potential to identify disease biomarkers with utility in evaluating current and novel therapies. MRS studies from seven patients with MPSII all receiving enzyme replacement therapy were compared with a large cohort of children with various neurocognitive disorders with normal MR imaging. All studies were completed on 1.5Tesla clinical MR scanners. Brain metabolite concentrations were determined from basal ganglia and parieto-occipital white matter using LCModel quantification. Serial trends in brain metabolites were analysed. Examination of mean spectra and quantitative metabolite concentrations demonstrated significantly decreased white matter N-acetylaspartate (a neuronal marker), total choline and glutamate, and elevated myo-inositol (glial marker) in MPSII patients. Analysis of serial determinations of white matter N-acetylaspartate demonstrated no change in two patients with stable MR imaging features but decreasing N-acetylaspartate in two patients more severely affected or deteriorating. These data demonstrate the utility of MRS to monitor serial alterations in brain metabolites including N-acetylaspartate which could be used as biomarkers of progressive neurological disease in MPSII. Integrated as an adjunct to MRI, such an approach could aid the evaluation of the efficacy of current ERT and also novel CNS-targeted therapies in MPSII.
KeywordsMagnetic Resonance Spectroscopy Enzyme Replacement Therapy Lysosomal Storage Disorder Hunter Syndrome Brain Metabolite
Mucopolysaccharidosis Type II
Central nervous system
Enzyme replacement therapy
Magnetic resonance spectroscopy
Magnetic resonance imaging
Details of funding
The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors. A.C.P. group funded in part by Cancer Research UK, EPSRC, MRC, NIHR Cancer Imaging Programme Grant. Birmingham Children’s Hospital Research Foundation (BCHRF 204 to J.E.D.). N.P.D. funded by CSO/NIHR Healthcare Scientist Fellowship. P.G. is a GSK Clinician Scientist Fellow.
Conflict of interest
C.J.H. has advisory board membership and has received honoraria, lecture fees and research grants from: Actelion, Shire, Biomarin and Genzyme. C.J.H. has had research funds, travel grants and lecture fees from patient organisations: NSPKU, MPS Society, National Diabetic foundation. C.J.H. is an expert advisor for both the MHRA and the EMEA.