Blockade of CD40-TRAF2 Interaction and IL-1 in Control of Inflammatory Disorders
- 详细技术说明
- As a pro-inflammatory molecule, CD40 and its ligand CD154 play a central role in the development and/or progression of a variety of diseases with an inflammatory component such as atherosclerosis, aut
- *Abstract
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As a pro-inflammatory molecule, CD40 and its ligand CD154 play a central role in the development and/or progression of a variety of diseases with an inflammatory component such as atherosclerosis, autoimmune disorders, Crohn's Disease, rejection of transplanted organs and stroke. Thus, the CD40-CD154 pathway has become an attractive therapeutic target for the treatment of a broad variety of human diseases. Clinical trials have been undertaken based on administration of a blocking anti-CD154 antibody for treatment of lupus nephritis, Crohn's disease and Immune Thrombocytopenic Purpura. While the anti-CD154 antibodies appeared clinically effective, some patients experienced heart attacks. This side effect was not caused by blockade of CD40 signaling but rather by an unexpected effect of the anti-CD154 antibody on platelets (platelet aggregation). Dr. Carlos Subauste has developed a different approach to block the effect of CD40 that should not cause platelet aggregation. Rather than employing an antibody-based approach to block CD40-CD154 signaling, Dr. Subauste has developed and identified through HTS agents that at low concentrations act intra-cellularly to block signals downstream of CD40 that drive inflammatory responses. The agents have been demonstrated to be highly effective in in vitro testing, and now, a proprietary in vivo model has also been developed to provide animal data.Recently, Dr. Subauste's lab has now tested an identified blocking peptide in vivo using mice. The peptide successfully inhibited inflammation. This has been done twice. The peptide also inhibits pro-inflammatory responses in vitro using human cells. Dr. Subauste also has continued with testing of the small molecules identified by their high throughput screening process. There is at least one compound that also inhibits inflammatory responses in human cells.
- 国家/地区
- 美国
