The company was founded in 2006 but already in 1992 Jan Olof G Karlsson (then at Nycomed Imaging in Oslo, now at Linköping University and retired from PledPharma since 2014) initiated preclinical studies to investigate the cardiovascular effects of the MRI contrast agent and mangafodipir. Later, Per Jynge (then at Trondheim University) and Rob Towart (then at Nycomed Pharma in Linz and later at Nycomed Innovation in Malmö) also joined in these studies.
It was discovered that mangafodipir had a vasodilatory effect by protecting nitric oxide (NO ·) from being eliminated by superoxide radicals (· O2–). They also assumed, as they later confirmed, that mangafodipir is a superoxide dismutase (SOD) mimetic, i.e. mangafodipir mimics the enzyme SOD which is one of the body’s most important protectors against oxidative stress. Mangafodipir and PLED substances (including PledOx®) belong to the substance class LowMEM (Low Molecular Enzyme Mimetics).
In connection with the discovery that mangafodipir had SOD mimetic activity, the idea came to use mangafodipir in the treatment of diseases with high level of oxidative stress resulting in cell damage, which occurs in e.g. cancer treatment and cardiovascular disease. Preclinical studies showed that mangafodipir protects the heart from doxorubicin (link to the study). Doxorubicin is one of the most effective cell toxins, but its use is severely limited by the fact that it causes very serious heart damage.
Preclinical results also showed that a metabolite for mangafodipir protected the heart from reperfusion injury (reflux injury) that occurs after, e.g. Percutaneous coronary intervention (PCI) in the treatment of acute myocardial infarction. Concomitant treatment with PLED substance during reperfusion reduced infarcts by more than 50% in pigs.