Progressive kidney disease is a global health burden most commonly caused by diabetes and obesity, which are dramatically on the rise. In Australia, 1 in 3 adults are at risk of developing chronic kidney disease (CKD) which has enormous economic consequences. This project will provide a proof of concept for a new drug which not only aims to prevent/delay CKD progression but to potentially reverse progressive renal failure which is critical for the health and wellbeing of 1.8 million Australians.
Kidney fibrosis is the inevitable consequence of an excessive accumulation of extracellular matrix (ECM) that occurs in virtually all chronic kidney disease (CKD) leading to irreversible end stage kidney disease. Strategies that target one pathway contributing to kidney fibrosis have failed in numerous clinical trials. Hence new agents targeting novel pathways to limit kidney fibrosis are critically needed. The proposed strategy is not dependent on inhibiting a single pathway leading to fibrosis, but rather aims to directly inhibit matrix protein cross-linking, mediated by lysyl oxidase-like 2 (LOXL2), that leads to irreversible fibrosis. We have recently demonstrated that lysyl oxidase-like 2 (LOXL2) expression is increased in human proximal tubule cells exposed to hypoxic conditions and in diabetic mice kidney. LOXL2 has been demonstrated to be overexpressed in multiple experimental models of renal fibrosis. The current project will determine whether LOXL2 inhibition can prevent and/or reverse renal fibrosis. Three models of renal injury, each of which reflect human disease will be studied. We will additionally assess the correlation of pathological change with plasma and urinary biomarkers. This will allow us to determine non-invasive markers of therapeutic efficacy in future clinical studies.
Dr Saad is a senior research fellow with a national and international reputation in the area of metabolic and renal disease. She has published extensively in the area. She has successfully supervised 8 PhDs, 6 MSc, 1 Honours, and 2 summer students to completion and is currently supervising 4 PhD students affiliated with the University of Sydney and 2 Honours students affiliated with the University of Technology Sydney (where she hold an Academic Honorary position). She has expertise in diabetic kidney disease, fibrosis, oxidative stress, mitochondrial function and mitochondrial DNA quantitation.
The opportunity ID for this research opportunity is 2208