Compugen Announces Positive In-Vivo Results for Therapeutic Peptide Candidate for Immune Related Diseases
News Jul 10, 2008
Compugen Ltd. has announced positive results from a recently completed in vivo study of CGEN-25007, a novel peptide antagonist of the gp96 protein.
The data indicate that CGEN-25007 has immunosuppressive effects and therapeutic potential for the treatment of various inflammatory diseases and other immune related pathologies.
CGEN-25007, which has been shown to bind to recombinant gp96 in a dose dependent manner, was initially predicted using the Company’s previously announced DAC blockers platform, which was designed to predict peptides that block proteins of interest from achieving certain disease-associated conformations.
Using an animal model of endotoxemia, a condition in which there is a substantial increase in the levels of inflammatory cytokines and chemokines in serum, CGEN-25007 was shown to exhibit a profound and dose-dependent anti-inflammatory activity.
In this study, the novel peptide was administered following the introduction of lipopolysaccharide (LPS), a bacterial substance that induces a strong response in the animal immune system leading to systemic inflammation.
The administration of CGEN-25007 resulted in a decrease of approximately 50% in the serum levels of inflammatory cytokines and chemokines, including tumor necrosis factor alpha (TNF-a), IL-6, interferon-gamma (IFN-?), MIP-1a and MIP-2.
In addition, in ex-vivo experiments CGEN-25007 was found to strongly inhibit the secretion of inflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) which had been challenged with LPS, staphylococcus epidermidis or anti-CD3 antibody, compounds known to activate the human immune system through different receptors.
PBMCs triggered with these compounds and treated with CGEN-25007 exhibited more than 80% inhibition of secretion of cytokines, including TNFa, IL-1ß, IL-6, IL-8, IL-12 and MIP-1a. In addition, CGEN-25007 had only a 20% inhibitory effect on the secretion of GM-CSF and no effect on the secretion of IL-2, suggesting selectivity in the action of this peptide.
These results support the potential use of this peptide as a novel approach for the treatment of many immune related diseases, including sepsis, autoimmune disorders, cardiovascular diseases and acute transplant rejection.