Scott D. Barnett, PhD
Dual Inhibition of sEH and COX-2 for the Treatment of Focal Segmental Glomerular Sclerosis
Summary
Focal segmental glomerulosclerosis (FSGS) is the single most common form of kidney disease. Unchecked, this devastating disorder leads to end stage renal disease (ESRD), a terminal diagnosis in the absence of a kidney transplant. The progression of FSGS is defined by damage to the glomerulus, the primary filter of blood in the kidney. This research seeks to better understand the protective effects of a family of small molecules found in the glomerulus called epoxyeicosatrienoic acids (EETs), as well as the potential adverse effects caused by their metabolism. PTUPB is a novel drug that has a two-fold action on EETs. First, it acts to prevent EET breakdown by inhibiting an enzyme called soluble epoxide hydrolase (sEH). Second, it limits the formation of EET metabolites though inhibition of cyclooxygenase-2 (COX-2). The objective of this research is to determine if PTUPB exerts a protective/therapeutic effect on glomerular function by limiting EET metabolism, while concurrently decreasing the amount of deleterious EET metabolites. The long-term goal of this study is to mitigate the glomerular damage caused by FSGS by better understanding the role of EETs and their metabolites in the kidney. The proposed research is innovative because it investigates a new class of renal therapeutics using pharmacology, physiology, and medicinal chemistry, and it will expand knowledge of the role of EET metabolites in FSGS. There is a dearth of effective treatment options for FSGS, and if successful, PTUPB will represent a new and much needed therapy for this common and lifethreatening disease.
As academic research scientists we live or die by our publications, grants, and other forms of professional achievement/recognition. This fellowship was an important first step for me as I seek to thrive in this challenging field. Importantly, it freed up funds in our lab to accelerate the pace of research, and through the PhRMA Foundation I have made contacts that will foster collaborations for years to come.
