As early as in 1992 Jan Olof G Karlsson (then at Nycomed Imaging in Oslo) initiated preclinical studies to explore potential cardiovascular effects of the MRI contrast agent and PLED-derivative mangafodipir. Per Jynge (then at Trondheim University) and Rob Towart (then at Nycomed Pharma in Linz and later at Nycomed Innovation in Malmö) joined Karlsson in these studies. It was discovered that mangafodipir had a vasodilating effect by protecting nitric oxide (·NO) from reacting with superoxide radicals (·O2–). It was hypothesized and later confirmed that mangafodipir is a superoxide dismutase (SOD) mimetic. Mangafodipir and other PLED-compounds (including PledOx®) belong to a class of compounds named LowMEM (Low Molecular Enzyme Mimetics)
In connection with the discovery that mangafodipir possessed SOD mimetic activity, the idea came up of using mangafodipir as a remedy against oxidative stress, appearing for instance during cancer treatment and in cardiovascular diseases. Studies in mice showed that mangafodipir protected the heart against the chemotherapy drug doxorubicin. Doxorubicin is one of the best agents for treating human hematological malignancies and solid tumors. Its use is, however, restricted by dose-related and irreversible cardiotoxicity.
It was also demonstrated that a metabolite of mangafodipir acts as cardioprotectant during reperfusion of acute myocardial infarction in pigs. It was shown that simultaneous administration of a PLED-derivative during reperfusion of an acute myocardial infarction, reduced infarct size by more than 50%.
Then one thing led to another and to cut a long story short it was demonstrated that mangafodipir could protect normal cells against cytotoxic/cytostatic drugs without interfering negatively with the anticancer effect of these drugs.
PledPharma was founded in 2006 by:
Professor emeritus Torsten Almén
Professor Ingemar Lundström
Division of Applied Physics, Linköping University, Linköping, Sweden
Professor Louis J Ignarro
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, USA.
Assistant Professor Jan Olof G. Karlsson
Jan Olof G. Karlsson has a PhD in pharmacology from Linköping University, Sweden, where he also became an assistant professor of pharmacology in 1991. Read more…
Professor Per Jynge
Division of Drug Research, Department of Medical and Health Sciences Linköping University, Sweden
Associate Professor Heidi Brurok
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
Dr Rob Towart
Audacter Consulting, Helensburgh, Scotland