Backed by a $200,000 grant from the Alliance for Lupus Research, Dr. Chandra Mohan, a biomedical engineer focusing on the genetics of systemic lupus erythematosus at the University of Houston, is aiming to help patients through his research and reduce the tens of thousands of annual hospitalizations caused by lupus nephritis, which impairs the patient´s ability to rid waste from their bodies due to inflamed kidneys
Dr. Mohan believes he can use specific drugs to target a molecular pathway activated in lupus. “Currently, management of lupus involves the use of nonspecific drugs, such as steroids, that suppress the immune system. Our lab, however, is trying to find out the exact molecular mechanisms that lead to lupus,” said Dr. Mohan in a news release from UH.
Similar to any disease, lupus encompasses a variety of signaling pathways that culminate in disease symptoms. Dr. Mohan explained, “These mechanisms belong to two classes. On the one hand, you have molecules and pathways that activate the immune system to attack your own body cells. The second set of molecules focus on the kidneys once the immune system is activated by lupus. Our present research and grant focuses on this second molecular cascade, and we want to see whether we can target the kidneys to offer therapeutics that lessen the chance of a patient developing kidney disease once they’ve developed lupus.”
To understand the molecular mechanisms of lupus, Dr. Mohan’s laboratory is focusing on a pathogenic cascade found in inflammatory diseases that involves high levels of kallikreins, bradykinin, and bradykinin receptor B1. The three molecules are related because kallikrein enzyme helps produce bradykinin, which then acts on either bradykinin receptor B1 or B2. Lupus is dominated by B1 activation, leading to inflammation and fibrosis in the kidneys and eventual kidney failure. Dr. Mohan strongly believes that by blocking B1 receptor activation using drug inhibitors, the inflammatory pathway can be blocked and the kidneys preserved. “To put it in perspective, lupus affects so many pathways and cells. So, if we are successful, this would be one of many different ways of attacking such a complex disease,” said Dr. Mohan.
Together with research assistant professor Yong Du, Dr. Mohan is working with a physical inhibitor of B1 to investigate its effects on patients with lupus nephritis. “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,” said Dr. Mohan. “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.”
Currently, the inhibitor is used in clinical trials to treat other kidney diseases and has already been established as a safe drug. Additionally, the production company sifted through many libraries of molecules to establish the drug as a potent inhibitor of B1, increasing its chances of efficacy. Together, these attributes may speed the transition of the drug to lupus nephritis clinical trials. “We do believe this drug would be more efficacious than the currently available steroids, which essentially dampen the entire immune system,” concluded Dr. Mohan.