title: Novel Zebrafish EAE model: A quick in vivo screen for multiple sclerosis.
abstract: BACKGROUND
  Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators.
  
  
  METHODS
  The EAE model was developed by disease induction with myelin oligodendrocyte glycoprotein - 35-55 (MOG) and observation of survival, clinical signs and body weight changes. We have validated this model using fingolimod. We have further performed detailed validation using dimethyl fumarate, dexamethasone and SR1001, which are known modulators of rodent EAE.
  
  
  RESULTS
  The immunization dose for the disease induction was observed to be 0.6mg/ml of MOG in CFA (Complete Freund's adjuvant), injected subcutaneously (s.c.) near spinal vertebrae. In the validation study with fingolimod, we have demonstrated the modulation of disease symptoms, which were also confirmed by histopathological evaluation. Furthermore, detailed validation with three other known drugs showed that our observations concur with those reported in conventional rodent models.
  
  
  CONCLUSIONS
  We have standardized and validated the adult zebrafish EAE model. This model can help get a quick idea of in vivo activity of drugs in a week using very low quantities of candidate compounds. Further work will be required to define this model particularly as it is found that zebrafish may not express a MOG homologue.
authors.affiliation: Drug Discovery Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad-500078, India; Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad-500046, India. Electronic address: pushkark@drils.org.
authors.forename: Pushkar
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad-500046, India.
authors.forename: Swapna
authors.initials: S
authors.lastname: Yellanki
authors.affiliation: Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad-500046, India.
authors.forename: Raghavender
authors.initials: R
authors.lastname: Medishetti
authors.affiliation: Drug Discovery Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad-500078, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad-500046, India; Kareus Therapeutics, SA. 40 Rue Fritz-Courvoisier, 2300 La Chaux-de-Fonds, Switzerland.
authors.forename: Uday
authors.initials: U
authors.lastname: Saxena
authors.affiliation: Drug Discovery Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad-500078, India. Electronic address: pyogee@hyderabad.bits-pilani.ac.in.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D000069462:Dimethyl Fumarate / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D010641:Phenotype; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014741:Video Recording; D015027:Zebrafish
chemical_list: D007155:Immunologic Factors; C558809:SR1001; D013449:Sulfonamides; D013844:Thiazoles; D003907:Dexamethasone; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride
keywords: Drug Discovery; Experimental autoimmune encephalomyelitis (EAE); Fingolimod (Gilenya); Multiple Sclerosis (MS); Myelin oligodendrocyte glycoprotein (MOG); Zebrafish