Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis

  • Immunol Invest. 2015;44(7):694-712. doi: 10.3109/08820139.2015.1085391.
Nourollah Ramroodi  1 ,  Masood Khani  2 ,  Zohre Ganjali  3 ,  Mohammad Reza Javan  4 ,  Nima Sanadgol  3  5 ,  Roghayeh Khalseh  6 ,  Hadi Ravan  7 ,  Ehsan Sanadgol  8 ,  Mohammad Abdollahi  5
Affiliations
  • 1. a Department of Neurology, Faculty of Medicine , Zahedan University of Medical Sciences , Zahedan , Iran .
  • 2. b Department of Immunology, Faculty of Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran .
  • 3. c Department of Biology, Faculty of Sciences , University of Zabol , Zabol , Iran .
  • 4. d Department of Immunology, Faculty of Medicine , Zabol University of Medical Sciences , Zabol , Iran .
  • 5. e Department of Pharmacy and Pharmaceutical Science Research Center , Tehran University of Medical Sciences , Tehran , Iran .
  • 6. f Department of Chemical Engineering , Babol Noushirvani University of Technology , Babol , Iran .
  • 7. g Department of Biology, Faculty of Science , Shahid Bahonar University of Kerman , Kerman , Iran , and.
  • 8. h Department of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
PMID: 26436854 DOI: 10.3109/08820139.2015.1085391
Abstract

Background and purpose: 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.

Conclusion: 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.

Keywords
BIO-1211; EAE; VLA4; multiple sclerosis; neuro-inflammation.
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