Final Report Summary - RADICAL PHARMACOLOGY (Free Radical Pharmacology: Generators, Targets and Therapeutic Implications)
This project aimed and achieved to establish and validate these new approaches and to co-develop matching diagnostics. My team identified NOX4 and NOX5 as novel, mechanism-based therapeutic targets for ischemic stroke and diabetic nephropathy; NOX1, in diabetic atherosclerosis and retinopathy. Here inhibitory drugs proved to be beneficial and this principle is now co-developed with a Swedish biotech company for clinical development. Also a detrimental role for high levels of NO and potentiation with ROS was found suggesting a possible combination therapy. Moreover, on the beneficial side, sGC, the NO receptor was found to be reduced in stroke and could be activated by e new compound class, now also in clinical development. This also reduced stroke size suggesting even a triple therapy may be possible.
These activities were scaled up to two major European networks as COST actions on NO (ENOG) and ROS (EU-ROS) as well as an Advanced Grant (RadMed), a EUROSTARS drug development programme and a H2020 application on ROS as a common mechanism explaining several comorbidities (COMMOX in PHC-03).
Collectively, we achieved transfer of our research from Australia to Europe and scientific breakthroughs towards an entirely new approach to “oxidative stress” with high socio-economically relevant impact. We look forward taking this now to direct patient benefit.