The main objective of this Phase II application is to continue in vitro and preclinical studies to evaluate a potential biologic therapeutic for septic shock. Phase I purified a TNF inhibitor that is homologous to human MRP-8, a molecule of unknown function. It was also discovered that nanomolar concentrations of this peptide could inhibit LPS-induced production of reactive nitrogen intermediates (RNI) by macrophages. Since overproduction of both TNF and RNI is implicated in the pathogenesis of septic shock, this new activity makes MRP-8 even more promising as a treatment for sepsis. Phase II plans are to clone the human gene for MRP-8, express, and purify the recombinant molecule. Purified rMRP-8 will be evaluated in vitro and in vivo models of sepsis and inflammation. In vitro studies will focus on determining RMRP-8's spectrum of activities and analyzing mechanism of action. In vivo studies will evaluate efficacy in mouse models of endotoxemia and sepsis and in a guinea pig model of LPS-induced adult respiratory distress syndrome. The results of these studies will be crucial to determine whether further clinical studies planned for Phase III are warranted.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44CA053006-03
Application #
3506817
Study Section
Special Emphasis Panel (SSS (B3))
Project Start
1990-08-03
Project End
1994-09-29
Budget Start
1993-09-30
Budget End
1994-09-29
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Panorama Research, Inc.
Department
Type
DUNS #
City
Sunnyvale
State
CA
Country
United States
Zip Code
94089