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Radical Medicine: Redefining Oxidative Stress

Final Report Summary - RADMED (Radical Medicine: Redefining Oxidative Stress)

Oxidative stress, i.e. the appearance of chemically aggressive oxygen molecules (ROS) in our body, is one of the most widely claimed disease mechanisms. The appearance of ROS has been correlated with aging as well as many acute and chronic degenerative diseases. In response, vitamins and antioxidants nourish a multi-billion-euro economy. However, the use of vitamins, without diagnosed vitamin deficiency, and anti-oxidants is not only ineffective, it even imposes health risks. Was the hypothesis that ROS may play a role in disease thus wrong? No. It just had to be approached in a completely different manner.
First, we and others established that ROS are by no means only destructive triggers of disease. Instead, seven genes are known in the human genome that have only one known function, to produce ROS. Why should evolution have preserved those genes, if they are only causing disease? As we now know they are involved in immunity, hormone synthesis, blood vessel formation, bone growth, and hearing to name a few. Any anti-oxidant will thus always interfere with some of these beneficial roles of ROS. Thus, their expected net effect may be neutral or, as indeed observed, negative. This explained decades of failures of testing anti-oxidants in clinical trials.
The second major achievement of RadMed was to take international leadership on an alternative therapeutic and diagnostic approach. RadMed identified sources of oxidative stress that at a given time-point in a given disease can become detrimental; in addition, RadMed identified ways of repairing ROS induced damage. These approaches have not ended at the experimental or research level. RadMed was extended for one year to allow completion of the clinical trial CIPER in patients with severe atherosclerosis. RadMed’s findings in diabetes-induced end-organ damage have led to phase II and III clinical trials by a Swiss biotech in diabetic nephropathy. Moreover, RadMed has been awarded by the ERC a proof-of-concept grant to explore both inhibition of ROS formation and repair of ROS damage in ischemic stroke, a high unmet medical need indication, which also led to a EUROSTAR drug discovery project with a Swedish biotech company.
To treat patients in such trials in a manner that the likelihood of benefit is very high, RadMed developed novel approaches to diagnose ROS dysfunction in patients and thereby stratify them for ROS related therapies. This approach has been picked up by a German biotech company and is now developed for routine clinical application as a blood-based test panel. Since it may also desirable to localise ROS in the body by advanced imaging techniques, RadMed developed a gold-standard for 3D-ROS visualisation.
Finally, by big data and systems medicine approaches, RadMed identified that the disease relevance of ROS is probably more limited to a smaller group of diseases than previously thought. This will allow to focus future research and prevent unnecessary approaches and trials.
To disseminate RadMed’s findings as much as possible amongst European scientists, clinicians and biotech as possible a Collaboration on Science and Technology (COST) action was founded and led by RadMed. Also, the lay press is increasingly picking up this new view on ineffective and even harmful use of vitamins and antioxidants. Unfortunately, only the food and over the counter pharmaceutical industries seem to somewhat resistant to accepting these findings and continue marketing their products.