In Search of a Foundation for Therapies to Block and Reverse Fibrosis

Fibrosis is a form of inappropriate scarring, connective tissue forming where it should not inside organs, destroying the structures necessary for correct function. Fibrosis is involved in many age-related diseases, notably in liver conditions, for example. Researchers have in the last couple of years made a few initial inroads in targeting cell behavior to reduce fibrosis in some organs, but there is still comparatively little that can be done for patients suffering fibrotic conditions. Better and more universal approaches to block the mechanisms of fibrosis are needed, but as the publicity materials here indicate, the process of discovery is still in comparatively early stages.

Researchers have utilized the new software tool to evaluate the perturbation status of many signaling pathways. This new system aimed to identify robust biomarkers of fibrotic disease and develop effective targeted therapy. Fibrosis, a progressive accumulation of extracellular matrix, can occur in a wide range of organs and potentially distort their structure and function; most commonly it affects lung and hepatic tissues, causing idiopathic pulmonary fibrosis (IPF) and liver fibrosis respectively. Fibrosis accounts for up to 45% of deaths in the developed world, yet to date no effective therapeutic treatment has been developed. "Currently, there are no approved anti-fibrotic remedies and no reliable fibrotic biomarker. Our system can detect hidden fibrotic molecular signatures based on a pathway network analysis, and identify specific fibrogenic molecular changes regardless of detecting platform and tissue of origin. Despite many efforts, fibrosis is often misdiagnosed. Our system is supposed to help with proper and timely diagnostic."

With broad screening across multiple fibrotic organs, the platform identified pathogenic pathways that served as potential targets for the anti-fibrotic therapy. This approach led to a selection of the list of small molecules and natural compounds by their ability to minimize the signaling pathway difference between a fibrotic and a healthy state of the tissue. Further work with provides promising opportunities to identify conserved biological pathways that play a critical role in fibrosis development. "We have discovered previously-undetected pro-fibrotic signatures in glaucoma, based on pathway analysis. This new knowledge will allow us to cooperatively select and develop anti-fibrotic small molecule interventions to minimize or reverse this fibrotic state, and restore the tissue to normal function."

Link: http://www.eurekalert.org/pub_releases/2016-07/imi-psi072916.php