Therapeutic strategies in Wilson disease: pathophysiology and mode of action
| Autor: | Ralf Weiskirchen, Wolfgang Stremmel |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
business.industry chemistry.chemical_element General Medicine Disease Pharmacology Copper Pathophysiology Copper Chelator 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Neurologic manifestation Pharmacotherapy chemistry Medicine Metallothionein 030211 gastroenterology & hepatology Mode of action business Review Article on Unresolved Basis Issues in Hepatology |
| Zdroj: | Ann Transl Med |
| ISSN: | 2305-5839 |
| Popis: | Wilson disease is a copper overload disease treatable with the chelators D-penicillamine and trientine to enhance urinary excretion or with zinc which predominantly inhibits absorption. By lifelong treatment a normal life expectancy and significant improvement of hepatic injury as well as neurologic manifestation is achievable. Here we evaluate the mode of action for effective therapy of Wilson disease. We postulate that there is no quantitative removal of copper from the liver possible. The therapeutic goal is the removal of toxic free copper (non-ceruloplasmin, but albumin bound copper). This is achievable by the induction of metallothionein which is accomplished by chelators and in particular by zinc. For control of therapy the option of a direct measurement of free copper would be preferable over the less reliable calculation of this fraction. A therapeutic challenge is still the full restoration of neurological deficits which can hardly be reached by the available chelators. Whether bis-choline-tetrathiomolybdate as intracellular copper chelator is an option has to be awaited. It is concluded that the goal of actual drug therapy in Wilson disease is the normalization of free copper in serum. |
| Databáze: | OpenAIRE |
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