title: Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis.
abstract: OBJECTIVE
  Some functional limitations and economic burden of therapeutic antibodies indicated that introducing of alternative therapeutic compounds with same or different mechanism of action could be worthwhile. In this regard small-molecule antagonists can have a wide range of impacts, so in this research, we examine the prophylactic effects of BIO-1211 [Very Late Antigen-4 (VLA4) blocker], in experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in comparison with commercial available medicine, Natalizumab (NTZ)].
  
  
  METHODS
  EAE was induced by subcutaneous immunization of myelin oligodendrocyte glycoprotein (MOG35-55) in 8-week-old C57BL/6 mice. During EAE induction, mice were separated to distinct groups and provided either BIO-1211 (5 and 10 mg/kg) or NTZ (5 mg/kg) and co-administration of these two compounds. After 21 days, neuro-inflammatory responses were analyzed using qRT-PCR, western blot, and ELISA methods. Pervade of immune cells to brain was examined by Evans blue staining and immunohistochemistry (IHC) analysis of specific markers of microglia/monocytes (CD11b) and leukocytes (CD45).
  
  
  RESULTS
  Targeted disruption of VLA4/VCAM1 interactions, by BIO-1211 agonist in mice, results in reduced cytokines expression, leukocyte trafficking, and inhibition of inflammatory responses in EAE (p < 0.01) in a dose-independent manner (data not shown). Mice treated with both BIO-1211 and NTZ exhibited a considerable depletion in the EAE clinical score, which correlated with decreased expression of TNF-α, IL-17, IFN-γ and pervade of CD11b(+) and CD45(+) cells into the cerebral cortex.
  
  
  CONCLUSIONS
  Our results indicated that BIO12-11 compound would be an useful tool to further understand the biological roles of VLA4/VCAM1 interactions, and could also be considered as EAE-suppressing agent.
authors.affiliation: a Department of Neurology, Faculty of Medicine , Zahedan University of Medical Sciences , Zahedan , Iran .
authors.forename: Nourollah
authors.initials: N
authors.lastname: Ramroodi
authors.affiliation: b Department of Immunology, Faculty of Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran .
authors.forename: Masood
authors.initials: M
authors.lastname: Khani
authors.affiliation: c Department of Biology, Faculty of Sciences , University of Zabol , Zabol , Iran .
authors.forename: Zohre
authors.initials: Z
authors.lastname: Ganjali
authors.affiliation: d Department of Immunology, Faculty of Medicine , Zabol University of Medical Sciences , Zabol , Iran .
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Javan
authors.affiliation: c Department of Biology, Faculty of Sciences , University of Zabol , Zabol , Iran .|e Department of Pharmacy and Pharmaceutical Science Research Center , Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Nima
authors.initials: N
authors.lastname: Sanadgol
authors.affiliation: f Department of Chemical Engineering , Babol Noushirvani University of Technology , Babol , Iran .
authors.forename: Roghayeh
authors.initials: R
authors.lastname: Khalseh
authors.affiliation: g Department of Biology, Faculty of Science , Shahid Bahonar University of Kerman , Kerman , Iran , and.
authors.forename: Hadi
authors.initials: H
authors.lastname: Ravan
authors.affiliation: h Department of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Sanadgol
authors.affiliation: e Department of Pharmacy and Pharmaceutical Science Research Center , Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002540:Cerebral Cortex / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009574:Nitro Compounds; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D039041:Integrin alpha4beta1; D009574:Nitro Compounds; D009842:Oligopeptides; D012333:RNA, Messenger; D013844:Thiazoles; C118154:BIO 1211; D017493:Leukocyte Common Antigens; C041747:nitazoxanide
keywords: BIO-1211; EAE; VLA4; multiple sclerosis; neuro-inflammation