title: RDP58, a novel immunomodulatory peptide, ameliorates clinical signs of disease in the Lewis rat model of acute experimental autoimmune encephalomyelitis.
abstract: The therapeutic value of a novel immunomodulatory peptide, RDP58, was investigated in the acute experimental autoimmune encephalomyelitis (EAE) model of Multiple Sclerosis (MS). RDP58 is a 10-amino acid peptide with two major activities: (i) inhibition of inflammatory TH1 cytokines such as TNFalpha, IFNgamma, and IL12 and (ii) up-regulation of heme oxygenase-1 (HO-1) expression. Experiments in which EAE-induced Lewis rats exhibit an acute monophasic episode of disease demonstrated that a single intracerebroventricular injection of RDP58 is effective in preventing clinical signs of disease. The therapeutic effect on disease activity was observed at all pre-onset administration times and at all doses tested. Consistent with disease activity in vivo, RDP58-treated animals had reduced cellular infiltration within the spinal cord along with decreased TNFalpha expression levels. The data in this proof of concept study support the premise that RDP58, as a platform molecule, may be a promising new therapeutic intervention in autoimmune and inflammatory diseases.
authors.affiliation: Department of Discovery Research, Sangstat Medical Corporation, Fremont, CA 94555, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: DeVry
authors.forename: Marybeth
authors.initials: M
authors.lastname: Valdez
authors.forename: Lan
authors.initials: L
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Katja
authors.initials: K
authors.lastname: Kotsch
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.forename: Roland
authors.initials: R
authors.lastname: Buelow
authors.forename: Suhasini
authors.initials: S
authors.lastname: Iyer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007276:Injections, Intraventricular; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C092373:allotrap