title: Reduced levels of alpha-1-antitrypsin in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a novel approach for a potential treatment.
abstract: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative motor neuron disease that involves activation of the immune system and inflammatory response in the nervous system. Reduced level of the immuno-modulatory and anti-inflammatory protein alpha-1-antitrypsin (AAT) is associated with inflammation-related pathologies. The objective of the present is to determine AAT levels and IL-23 in the cerebrospinal fluid (CSF) of ALS patients and control group.
  
  
  
  CSF samples from newly diagnosed ALS patients and age-matched controls were analyzed for AAT and IL-23 by ELISA and magnetic luminex screening, respectively. A statistically significant reduction of 45 % in mean AAT levels was observed in the CSF of ALS patients (21.4 μg/ml) as compared to the control group (mean 38.8 μg/ml, p = 0.013). A statistically significant increase of 30.8 % in CSF mean levels of the pro-inflammatory cytokine IL-23 was observed in ALS patients (1647 pg/ml) in comparison to the controls (1259 pg/ml, p = 0.012). A negative correlation coefficient (r = -0.543) was obtained by linear regression analysis of the two measured parameters (p = 0.036).
  
  
  
  Reduced AAT and elevated IL-23 CSF levels support the notion of neuroinflammatory process occurring in ALS patients. Increasing AAT levels in the patients' nervous system should be further investigated as a new therapeutic approach and a novel potential tool for ALS treatment.
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, POB 12065, 91120, Jerusalem, Israel. wormser@cc.huji.ac.il.|David R. Bloom Center for Pharmacy at the Hebrew University and, The Dr. Adolf and Klara Brettler Centre for Research in Molecular Pharmacology and Therapeutics at the Hebrew University, Jerusalem, Israel. wormser@cc.huji.ac.il.
authors.forename: Uri
authors.initials: U
authors.lastname: Wormser
authors.affiliation: Department of Neuroscience, S. Agostino- Estense Hospital, and University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.affiliation: Research Centre for Environmental, Genetic and Nutritional Epidemiology (CREAGEN), University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Vinceti
authors.affiliation: Department of Neuroscience, S. Agostino- Estense Hospital, and University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fini
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer Sheva, 84105, Israel.
authors.forename: Amnon
authors.initials: A
authors.lastname: Sintov
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, POB 12065, 91120, Jerusalem, Israel.
authors.forename: Berta
authors.initials: B
authors.lastname: Brodsky
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, POB 12065, 91120, Jerusalem, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Proskura
authors.affiliation: Service and Unit of Neurology and Toxicology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Finkelstein
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000628:therapy*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D053759:Interleukin-23 / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D000515:alpha 1-Antitrypsin / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D053759:Interleukin-23; D000515:alpha 1-Antitrypsin
keywords: ALS; Amyotrophic lateral sclerosis; Antitrypsin; Cerebrospinal fluid; MND; Motor neuron disease