title: Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: a survey clinic-based study.
abstract: The aim of this study was to determine if blood chitotriosidase (Chit) activity and lysosomal enzyme levels might represent markers of disease activity and progression in amyotrophic lateral sclerosis (ALS). It is a survey clinic-based study performed in a tertiary ALS centre. Blood samples were obtained from 76 patients with ALS in different stages of the disease and from 106 healthy individuals serving as controls. Chit activity and the levels of acid alpha-glucosidase, acid alpha-galattosidase A, beta-glucocerebrosidase, and alpha-l-iduronidase were detected using the dried blood spots (DBS) technique. The CHIT1 genotype for exon 10 duplication and for the p.G102S variant was also determined. Chit activity was significantly higher in ALS patients than in healthy individuals. This difference was independent of the genotypes at CHIT1 functional variants. Chit were significantly higher in 34 rapidly progressing patients as compared to 42 with slowly progressive disease. Acid alpha-glucosidase was higher than normal and significantly correlated with the severity of the disease. Glucocerebrosidase and alpha-l-iduronidase activity were significantly lower in patients than in the controls. Alpha-galactosidase A was higher than normal only in rapidly progressing patients. We have employed a very simple and affordable laboratory test to measure blood Chit and lysosomal enzymes activity which could be easily included in the screening of ALS patients recruited in clinical trials. Remarkably, high levels of chitinase and alpha-galactosidase A could help to distinguish patients with fast progression from those with slow progression of the disease and possibly to follow the effects of treatments on neuroinflammation and autophagy.
authors.affiliation: Department of Pediatric and Newborn Screening, University of Torino, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Pagliardini
authors.affiliation: Department of Pediatric and Newborn Screening, University of Torino, Italy.
authors.forename: Severo
authors.initials: S
authors.lastname: Pagliardini
authors.affiliation: Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases, A. Avogadro' University, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Corrado
authors.affiliation: Department of Neurology, A. Avogadro' University, Maggiore della Carità University Hospital, Novara, Italy.
authors.forename: Ausiliatrice
authors.initials: A
authors.lastname: Lucenti
authors.affiliation: Department of Pediatric, A. Avogadro' University, Maggiore della Carità University Hospital, Novara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Panigati
authors.affiliation: Department of Neurology, A. Avogadro' University, Maggiore della Carità University Hospital, Novara, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bersano
authors.affiliation: Department of Neurology, A. Avogadro' University, Maggiore della Carità University Hospital, Novara, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Servo
authors.affiliation: Department of Neurology, A. Avogadro' University, Maggiore della Carità University Hospital, Novara, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantello
authors.affiliation: Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases, A. Avogadro' University, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.affiliation: Department of Neurology, A. Avogadro' University, Maggiore della Carità University Hospital, Novara, Italy. Electronic address: mazzini.l@libero.it.
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics; D015415:Biomarkers / Q000097:blood*; D002688:Chitinases / Q000097:blood; D018450:Disease Progression; D005260:Female; D006596:Hexosaminidases / Q000097:blood* / Q000235:genetics; D006801:Humans; D007068:Iduronidase / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D000519:alpha-Galactosidase / Q000097:blood*; D000520:alpha-Glucosidases / Q000097:blood
chemical_list: D015415:Biomarkers; D006596:Hexosaminidases; C086400:chitotriosidase; D002688:Chitinases; D000520:alpha-Glucosidases; D000519:alpha-Galactosidase; D007068:Iduronidase
keywords: ALS; CHIT1 polymorphisms lysosomal enzymes; biomarkers; chitotriosidase; neuroinflammation