Review on emerging polymer therapeutics of iron and copper overload

Scientists from the Department of Supramolecular Polymer Systems published a review article „Chelators for treatment of iron and copper overload: shift from low-molecular-weight compounds to polymers“ envisioned the dawn of polymer iron- and copper-chelating therapeutics for the treatment of hemochromatosis and Wilson´s disease and critically compared their advantages and disadvantages over conventional low-molecular-weight chelators.  The review was written in collaboration with colleagues from 1st Medical Faculty, Charles University and from Helmholz-Zentrum Dresden-Rossendorf in Germany. The article have been published in the journal Polymers.

The essential elements iron and copper are needed for the proper function of redox processes in every organism, and their metabolism is strictly regulated. Deficiencies of iron and copper are common and are reviewed elsewhere. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in multiorgan damage. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson’s disease. The damage of the organism may become fatal if untreated.

The main organ damaged is always the liver, as it is the key storage organ for both iron and copper, but also more specific organ damages (e.g., of the neural system for copper or of gonads for iron) occur. The current state of the art iron and copper overload therapies mostly rely on low-molecular-weight chelators. As these low-molecular-weight metal chelators possess strong side effects (e.g., ophthalmic and auditory toxicity; pulmonary, renal and neurological effects for deferoxamine or gastrointestinal problems; leucopenia and liver problems for penicillamine), new treatment paradigms are to be discovered, for which polymers hold great promise. „The purpose of this review article is to critically compare the advantages and disadvantages of currently developed polymer-based treatment approaches for iron and copper overload with a special focus on the correlation structure–properties–function–observed advantages/disadvantages and to propose new ways ahead,“ explains dr. Martin Hrubý, head of the Department of Supramolecular Polymer Systems.


Simplified overview of iron metabolism and iron flow in organism shows where the overload occurs due to hemochromatosis and thalassemia and where the effect of both low-molecular-weight and polymer drugs effect takes place.

 

The Original Article

Overview of Scientific Publications of the IMC