TAT-BH3 methods for treating arthritis

摘要

The present invention is directed to compositions and methods for treating immune system mediated disease. In particular, certain embodiments of the present invention use BH3 mimetic therapy as an efficacious treatment of the effector phase of RA wherein the compositions and methods of the present invention markedly reduce the level of the Bcl-2 antagonist protein Bim present in RA synovial tissue as compared to control patients. Therefore, the present invention involves restoring the function of Bim in order to ameliorate inflammatory arthritis. In connection therewith, systemic delivery of a peptide to the BH3 domain of Bim effectively inhibits the development of K/B×N serum transfer-induced arthritis which closely resembles the effector phase of RA.

主权项

1. A method of treating an immune-mediated disease in a patient comprising the step of:
administering a pharmaceutical composition to said patient in need thereof, said composition including a cell delivery agent that is a cell-penetrating peptide selected from the group consisting of TAT, penetratin, VP22, transportan, synthetic oligoarginines, and combinations thereof that is conjugated to a cell death agent that is the BH3 domain of Bim, in an amount sufficient to provide a clinically observable improvement in the disease symptoms of said patient; wherein said immune-mediated disease is selected from the group consisting of rheumatoid arthritis and juvenile polyarticular rheumatoid arthritis.