title: Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses.
abstract: The gangliosidoses (Tay-Sachs disease, Sandhoff disease, and GM1-gangliosidosis) are progressive neurodegenerative diseases caused by lysosomal enzyme activity deficiencies and consequent accumulation of gangliosides in the central nervous system (CNS). The infantile forms are distinguished from the juvenile forms by age of onset, rate of disease progression, and age of death. There are no approved treatments for the gangliosidoses. In search of potential biomarkers of disease, we quantified 188 analytes in CSF and serum from living human patients with longitudinal (serial) measurements. Notably, several associated with inflammation were elevated in the CSF of infantile gangliosidosis patients, and less so in more slowly progressing forms of juvenile gangliosidosis, but not in MPS disease. Thirteen CSF and two serum biomarker candidates were identified. Five candidate biomarkers were distinguished by persistent elevation in the CSF of patients with the severe infantile phenotype: ENA-78, MCP-1, MIP-1α, MIP-1β, and TNFR2. Correspondence of abnormal elevation with other variables of disease-i.e., severity of clinical phenotype, differentiation from changes in serum, and lack of abnormality in other neurodegenerative lysosomal diseases-identifies these analytes as biomarkers of neuropathology specific to the gangliosidosis diseases.
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA; Advanced Therapies Program, University of Minnesota-Fairview, Minneapolis, MN 55455, USA; Gene Therapy Center, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: jutz1@fairview.org.
authors.forename: Jeanine R Jarnes
authors.initials: JR
authors.lastname: Utz
authors.affiliation: Gene Therapy Center, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Crutcher
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA; Advanced Therapies Program, University of Minnesota-Fairview, Minneapolis, MN 55455, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA; Advanced Therapies Program, University of Minnesota-Fairview, Minneapolis, MN 55455, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sorgen
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA; Advanced Therapies Program, University of Minnesota-Fairview, Minneapolis, MN 55455, USA; Gene Therapy Center, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid*; D002490:Central Nervous System / Q000378:metabolism; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid; D054407:Chemokine CCL4 / Q000134:cerebrospinal fluid; D054365:Chemokine CXCL5 / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D005260:Female; D005733:Gangliosidoses / Q000175:diagnosis* / Q000378:metabolism; D016537:Gangliosidosis, GM1 / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000175:diagnosis*; D008297:Male; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000134:cerebrospinal fluid; D012497:Sandhoff Disease / Q000175:diagnosis / Q000378:metabolism; D013661:Tay-Sachs Disease / Q000175:diagnosis / Q000378:metabolism; D014157:Transcription Factors / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; C486263:CXCL5 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D054365:Chemokine CXCL5; C114015:MNP-1 protein, human; D047889:Receptors, Tumor Necrosis Factor, Type II; D014157:Transcription Factors
keywords: GM1-gangliosidosis; Ganglioside; Glycosphingolipid; Metabolomic; Sandhoff disease; Tay–Sachs disease