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Polymer Therapeutics for Oral Treatment of Wilson´s Disease

New medicament suitable for treating Wilson´s disease were designed, prepared and tested. Prepared materials are specific to copper chelation in biological environment and biologically inert. Properties of these medicaments allow applying this therapy without burdensome side effects, which are present during current therapies.

New biomaterials are based on modified cellulose and crosslinked chitosan with covalently bound copper chelator as potential drugs for the treatment of Wilson’s disease. We proceeded from the fact that copper is absorbed into the body by the gastrointestinal tract. Newly designed biopolymers are not degradable in human digestive tract and serve as copper scavengers. Our new proposed therapy utilizes specific copper chelating agent (8-hydroxyquinoline) that is covalently bound to carriers: cellulose or chitosan. New biocompatible carriers provide scavenging of copper without organ deposition. Described compounds are eliminated through the feces after oral administration. We have shown that both biopolymers are able to prevent the absorption of copper.

The greatest significance lies in the finding of very low copper content in the livers of animals after oral administration of radioactive isotope 64Cu. The biopolymers are able to scavenge radioactive isotope 64Cu and are fully eliminated from the body by the feces. Its released forms are degradable in the nature. This new way of treating Wilson´s disease can avoid harmful side effects which are typical for low molecular therapeutics and zinc therapy. Modified cellulose and chitosan are promising tools for the non-stressful treatment of Wilson’s disease. Proposed material can be used as nutrient supplement that can help patients all around the world.

Complete in vitro and successful in vivo biological evaluation on Wistar rats (72 samples) using radioactive 64Cu.

1. Skodova M, Kucka J, Vetrik M, Skopal J, Walterova Z, Sedlacek O, et al. Chelating polymeric particles intended for the therapy of Wilson's disease. Reactive and Functional Polymers 2013;73:1426-31. 2. Mattová J, Poučková P, Kučka J, Škodová M, Vetrík M, Štěpánek P, et al. Chelating polymeric beads as potential therapeutics for Wilson’s disease. European Journal of Pharmaceutical Sciences. 2014;62:1-7.

PV 2015-770: Polymers based on polysaccharides and ist use for Wilson´s Disease treatment PCT/CZ2016/050039

Institute of Macromolecular Chemistry of Academy of Sciences of the Czech Republic, v.v.i. Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University in Prague, Salmovska 1, 120 00 Prague 2