Sepsis a serious life-threatening condition resulting from a harmful inflammatory reaction of the body due to bacterial infection. The mortality rate of sepsis remains high in intensive care units around the world but therapeutic interventions have been largely unsuccessful. Clearly, there is a great need for inventing efficacious therapeutic drugs to treat patients with sepsis associated illnesses. Increasing evidence indicates that aberrant apoptosis (programmed cell death) plays a key role in sepsis-related death but currently no drugs to prevent apoptosis in sepsis are available for clinical use. A soluble decoy receptor, DcR3, has been demonstrated for its survival effects in animal lethality induced by apoptosis. Moreover, the level of DcR3 was significantly elevated in human cells in response to bacterial antigens and in sera of patients with bacterial infections thus indicating that the protein might play an important role in the pathogenesis of bacterial infection and sepsis. Therefore, we propose to accomplish two goals in this Phase-I STTR study. First, we propose to develop a high quality soluble recombinant human DcR3 (rhDcR3) so that the protein can be safe and effective for preclinical and future clinical studies. The protein will be purified, PK studies conducted. Second, to evaluate the future therapeutic potential of rhDcR3 to treat septic patients, we propose to test whether the protein provides a survival advantage in an animal model of sepsis. Undoubtedly, the positive outcome of this project will provide us with the rationale for further development of rhDcR3 for future clinical use. If DcR3 can be effective for treating patients with sepsis, this will increase the success rate of therapy thus reducing the burden of medical care costs, as well as enhancing the quality of the patients' life
