Novel HIV-derived peptides for the treatment of T-cell related disorders.
Autoimmune diseases affect millions of individuals worldwide and the cost of these diseases, in terms of actual treatment expenditures and lost productivity, is measured in billions of dollars annually. Uncontrolled activation of T cells is a hallmark of many autoimmune diseases; prominent among these are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and Type I diabetes. T cells also play a cardinal role in the rejection for organ transplantation or graft versus host disease. Currently available therapies such as immunosuppressive drugs suppress the patient's entire immune response, thereby increasing the risk of infection, and can cause toxic side effects to non-lymphoid tissues. The development of new immunosuppressive agents capable of selectively inhibiting the activation of T lymphocytes with minimal side effects is therefore desirable. The present invention provides novel peptides endowed with immunosuppressive activity, for the treatment of T-cell related conditions such as autoimmune, inflammatory and graft rejection disorders.
• Treatment of various T-cell mediated pathologies including:
• Autoimmune diseases.
• Inflammatory disorders.
• Graft rejection and graft-versus-host disease (GVHD).
- The peptides exhibit minimal toxicity.
- The peptides are about 20 times more potent than the strongest peptide reported from the HIV envelope proteins.
- The peptides are less hydrophobic than other gp41-derived peptides and as such are more readily soluble in aqueous solution.
A team of scientists from the Weizmann Institute has developed peptides, derived from the ectodomain of the HIV gp41 envelope protein, that are able to effectively inhibit T cell activation. These peptides are 20-fold more potent as immunosuppressive peptides compared to other HIV-derived immunosuppressive peptides. The novel gp41-derived peptides robustly attenuated autoimmune disease in vivo, as shown in an experimental autoimmune encephalomyelitis (EAE) animal model, while demonstrating minimal toxic effect in both in vivo and in vitro studies. Furthermore, the novel peptides are remarkably less hydrophobic than other HIV-derived peptides, and therefore can readily dissolve, facilitating their administration as therapeutic agents.