Specifically, Mohan is referring to a pathogenic cascade found in inflammatory kidney diseases, which includes three molecules kallikreins, bradykinin and one of two bradykinin receptors. High levels of these three specific molecules work together to cause the disease.
The kallikrein enzyme leads to the production of bradykinin, which is a peptide that helps regulate blood pressure and inflammation. The kidneys also have elevated levels of the two bradykinin receptors (B1 and B2), which are proteins that chemically bond with bradykinin to set certain biological processes in motion. While the B2 receptor plays a role in disease protection, the B1 receptor induces inflammation and fibrosis in the kidneys, eventually leading to kidney failure. In lupus patients, B1 is more prevalent. The goal of the ALR grant is to determine whether this pathway can be blocked, thus preventing the activation of certain receptors in the kidneys.
Mohan and his research team, including research assistant professor Yong Du, are working with a drug already in clinical trials for other kidney diseases. This drug acts as an inhibitor that attaches to B1 and physically blocks it from bonding with bradykinin. No bond means no kidney inflammation. Mohan's group will study how subjects with lupus nephritis respond to this inhibitor drug.
"We will compare the efficacy of this novel therapy with that of steroids, which is currently the most common standard of care, in suppressing lupus nephritis," Mohan said. "If these subjects show significant improvement, we will have established the link between lupus nephritis and the pathogenic cascade we are targeting, as well as show that the inhibitor is an excellent candidate for treating lupus nephritis."
Mohan believes there is a high chance this will work, since the company that developed the drug has already gone through many libraries of molec
|Contact: Lisa Merkl|
University of Houston