Clinical management of Wilson disease

Abstract

The availability of effective therapies distinguishes Wilson disease (WD) from other inherited neurometabolic diseases. The cause of hepatic, neurologic or psychiatric symptoms is copper overload and subsequent copper toxicity. Diagnosed WD patients require life-long pharmacologic therapy that is focused on reversal of copper overload with maintenance of a long-term negative copper balance. This is associated with the rapid control of free or non-ceruloplasmin bound copper that is mostly responsible for acute cytotoxic effects. Currently available therapies can be divided into chelators and zinc salts. They have different mechanisms of action and the onset of efficacy that influences their selection in acute and chronic stages of therapy. We review the use of D-penicillamine and trientine for chelation therapies, including the required monitoring of therapy for its efficacy and possible overtreatment with iatrogenic copper deficiency.Additionally, the use of zinc salts is also discussed, including a possibility of its use for the initial therapy in an acute stage of the disease. Supportive and symptomatic therapies for liver failure and neuropsychiatric symptoms are also reviewed.

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

“…Kontoghiorghes et al [71,75] reported a number of fatal renal, liver, and bone marrow failures due to Deferasirox. Another common CA used for Cu overload, D-Penicillamine, causes neuropsychiatric or hepatic complications in up to one-third of patients [76]. Toxic effects have also been observed with other CAs (2,3-dimercaptopropanol, meso-2,3-dimercaptosuccinic acid, 2,3-dimercaptopropane-1-sulfonic acid, EDTA calcium or sodium salts) used in the therapy for the overload of As, Au, Hg, Pb [77].…”

The Patient-Reported Experience of Living with Wilson Disease

“…Wilson disease is fatal without proper management [6] and there is no curative treatment. Zinc and copper chelators are currently used for reducing copper levels and managing the disease [11,15,16]. As an exploration into potential treatments is pursued, there is a need to better understand how patients describe their experience with Wilson disease and to identify the symptoms and impacts of most importance in an understudied condition.…”

Current Biomedical Use of Copper Chelation Therapy

“…These drugs, however, need further studies both in vitro and in vivo as they have not been used in clinical trials so far. An updated overview on the currently approved treatments for Wilson's clinical manifestation is reported in several recently published reviews [27,47,48] focused on the efficiency, the side efaafects and possible combination therapies.…”