RDP58, a novel immunomodulatory peptide, ameliorates clinical signs of disease in the Lewis rat model of acute experimental autoimmune encephalomyelitis.
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.
DeVry
Christopher G
CG
Department of Discovery Research, Sangstat Medical Corporation, Fremont, CA 94555, USA.
Valdez
Marybeth
M
Gao
Lan
L
Wang
Jing
J
Kotsch
Katja
K
Volk
Hans-Dieter
HD
Bechmann
Ingo
I
Buelow
Roland
R
Iyer
Suhasini
S
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
D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C092373:allotrap