Hurler Syndrome Glycosaminoglycans Decrease in Cerebrospinal Fluid Without Brain-Targeted Therapy

Overview

Journal Ann Neurol

Specialty Neurology

Date 2023 Sep 7

PMID 37679306

Authors

Troy C Lund

Elizabeth Braunlin

Lynda E Polgreen

Ashish O Gupta

Paul J Orchard

Julie B Eisengart

Affiliations

Soon will be listed here.

Abstract

Novel therapies for Hurler syndrome aim to cross the blood-brain barrier (BBB) to target neurodegeneration by degrading glycosaminoglycans (GAG). BBB penetration has been assumed with decreased cerebrospinal fluid (CSF) GAG, yet little is known about CSF GAG without brain-targeting therapies. We compared pre-transplant CSF GAG in patients who were treatment naïve (n = 19) versus receiving standard non-BBB penetrating enzyme replacement therapy (ERT, n = 12). In the ERT versus treatment naïve groups, CSF GAG was significantly lower across all content assayed, raising questions about using CSF GAG decrements to show BBB penetration. Future studies should compare GAG reduction in standard versus novel therapies. ANN NEUROL 2023;94:1182-1186.

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