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 autoinumme encephalomyelitis (EAE) model of Multiple Sclerosis (MS). RDP58 is a 10-amino acid peptide with two major activities: (i) inhibition of inflammatory T(H)1 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. (C) 2004 Elsevier B.V. All rights reserved.