Fibrotic disease is characterised by excessive scarring and tissue hardening and is the major pathological component contributing to a variety of different diseases that ultimately result in organ failure (e.g. cirrhosis of the liver, idiopathic pulmonary fibrosis, chronic kidney disease, endomyocardial fibrosis, amongst many others). The lack of effective drug treatments for fibrotic diseases often means that transplant surgery is the only treatment option and in many cases these diseases are fatal. Fibrotic disease is estimated to account for approximately 43 per cent of deaths from disease in the developed world, representing a major unmet medical need. It is also the major cause of hospitalisations in Australia.
Our group has identified a novel target and developed new sphingolipid modifying agents for the treatment of fibrosis. Our background work is the first to link sphingolipid modification to fibrosis and we are the first group to develop drug-like (orally bioavailable) inhibitors of sphingolipid modifying agents (patented). Sphingolipid modifying agents regulate the relative levels of sphingolipids that are known to have opposing effects on multiple signal transduction pathways involved in fibrosis. In this project we brought together experts in the fields of medicinal chemistry, cell biology, clinical cardiology, and drug discovery and development to undertake preclinical proof-of-concept studies of sphingolipid modifying agents in fibrosis.