Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of Gaucher disease

PloS One
Hila ZigdonA H Futerman

Abstract

Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available.

References

Mar 1, 1994·The Journal of Clinical Investigation·C E HollakJ M Aerts
May 23, 2002·Human Molecular Genetics·Rachel MyerowitzRichard L Proia
Oct 4, 2002·Muscle & Nerve·P L McGeer, E G McGeer
Dec 14, 2004·Molecular Genetics and Metabolism·Rachel MyerowitzRichard L Proia
Jan 15, 2005·Neurobiology of Disease·Dori PelledAnthony H Futerman
Apr 9, 2005·The Journal of Biological Chemistry·Lakshmanane PremkumarJoel L Sussman
Oct 19, 2006·Journal of Biomedicine & Biotechnology·Kathleen S HruskaEllen Sidransky
Mar 16, 2007·Journal of Leukocyte Biology·Kate SchroderMatthew J Sweet
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vera M RipollDavid A Hume
Oct 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ida Berglin EnquistStefan Karlsson
Dec 11, 2008·Annals of Neurology·Raphael SchiffmannAshok Vellodi
Oct 23, 2009·The New England Journal of Medicine·E SidranskyS G Ziegler
Oct 27, 2009·Pediatric Rheumatology Online Journal·Rolando CimazBernhard Manger
Oct 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Pramod K MistryMone Zaidi
Jul 30, 2011·PloS One·William BenkoEdmond J Fitzgibbon
Apr 28, 2012·Journal of Proteome Research·Christian D KelstrupJesper V Olsen
May 24, 2012·Human Molecular Genetics·Celine V M CluzeauForbes D Porter
Aug 15, 2012·Scientific Reports·Hirotaka TanakaHideaki Hara
Apr 9, 2013·Handbook of Experimental Pharmacology·Einat B Vitner, Anthony H Futerman
Apr 30, 2013·Handbook of Clinical Neurology·Cyril MignotThierry Billette De Villemeur
Jan 21, 2014·Nature Medicine·Einat B VitnerAnthony H Futerman
Apr 15, 2014·Nature Biotechnology·Juan A VizcaínoHenning Hermjakob

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Citations

Jan 9, 2016·Neurochemistry International·Melinda BarkhuizenAnne F Grobler
Mar 8, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·John MarshallSeng H Cheng
Dec 23, 2016·Blood Cells, Molecules & Diseases·Vagishwari MurugesanPramod K Mistry
Sep 1, 2017·Molecular Neurobiology·Kevin M BudgeFayez F Safadi
Oct 28, 2018·Applied and Environmental Microbiology·Barak DrorDani Eshel
Jul 25, 2019·Journal of Neuroinflammation·Penelope J HallettOle Isacson
May 22, 2020·Molecular Neurobiology·Kevin M BudgeFayez F Safadi
May 14, 2016·Journal of Neuroinflammation·Einat B VitnerAnthony H Futerman
Nov 14, 2019·Journal of Molecular Neuroscience : MN·Shaochun ZhuMiles Trupp
Oct 21, 2018·Acta Neuropathologica Communications·Melanie HüttenrauchOliver Wirths
Dec 28, 2018·International Journal of Molecular Sciences·Martijn J C van der LiendenMarco van Eijk
Mar 19, 2020·Journal of Clinical Medicine·Daphne E C BoerJohannes M F G Aerts
May 29, 2016·The Journal of Pathology·Ayelet VardiAnthony H Futerman
Jan 10, 2021·Molecular Genetics and Metabolism·Gregory A GrabowskiPramod K Mistry
May 1, 2021·International Journal of Molecular Sciences·Marco van Eijk, Johannes M F G Aerts
May 6, 2021·Alzheimer's Research & Therapy·Freyja AichholzerOliver Wirths
Jun 1, 2021·Frontiers in Immunology·Marina SaadePaula Fernanda Kinoshita
Sep 1, 2021·Neurobiology of Disease·Robert BrendzaBrad A Friedman
Apr 29, 2020·Dementia and Geriatric Cognitive Disorders·Ione O C WoollacottJonathan D Rohrer

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Datasets Mentioned

BETA
PXD001654

Methods Mentioned

BETA
protein assay
ELISA
FACS

Clinical Trials Mentioned

NCT00041535

Software Mentioned

Mascot
TransOmics

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