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

Troy C. Lund; Elizabeth Braunlin; Lynda E. Polgreen; Ashish O. Gupta; Paul J. Orchard; Julie B. Eisengart

doi:10.1002/ana.26786

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

Troy C. Lund, Elizabeth Braunlin, Lynda E. Polgreen, Ashish O. Gupta, Paul J. Orchard, Julie B. Eisengart

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1182-1186
Number of pages	5
Journal	Annals of Neurology
Volume	94
Issue number	6
DOIs	https://doi.org/10.1002/ana.26786
State	Published - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Access

10.1002/ana.26786

OpenUrl availability

Full text

Cite this

@article{a56624671c284bbbaac1cf2cf7366fa7,

title = "Hurler Syndrome Glycosaminoglycans Decrease in Cerebrospinal Fluid without Brain-Targeted Therapy",

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 na{\"i}ve (n = 19) versus receiving standard non-BBB penetrating enzyme replacement therapy (ERT, n = 12). In the ERT versus treatment na{\"i}ve 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.",

author = "Lund, {Troy C.} and Elizabeth Braunlin and Polgreen, {Lynda E.} and Gupta, {Ashish O.} and Orchard, {Paul J.} and Eisengart, {Julie B.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2023",

month = dec,

doi = "10.1002/ana.26786",

language = "English (US)",

volume = "94",

pages = "1182--1186",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "6",

}

TY - JOUR

T1 - Hurler Syndrome Glycosaminoglycans Decrease in Cerebrospinal Fluid without Brain-Targeted Therapy

AU - Lund, Troy C.

AU - Braunlin, Elizabeth

AU - Polgreen, Lynda E.

AU - Gupta, Ashish O.

AU - Orchard, Paul J.

AU - Eisengart, Julie B.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85171752549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85171752549&partnerID=8YFLogxK

U2 - 10.1002/ana.26786

DO - 10.1002/ana.26786

M3 - Article

C2 - 37679306

AN - SCOPUS:85171752549

SN - 0364-5134

VL - 94

SP - 1182

EP - 1186

JO - Annals of Neurology

JF - Annals of Neurology

IS - 6

ER -

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

Abstract

Bibliographical note

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this