The Treatment of Wilson's Disease, a Rare Genetic Disorder of Copper Metabolism

Abstract

Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.

Oral Zinc Supplementation Decreases the Serum Iron Concentration in Healthy Schoolchildren: A Pilot Study

“…For example, in Wilson’s disease, zinc can induce copper binding metallothionein in duodenal enterocytes and in hepatocytes. Thus, copper absorption into the circulation is reduced, thereby decreasing the damaging effects of free copper [36]. This negative balance of copper in turn might affect iron transport and contribute to the risk of anemia in children [33].…”

Pathological mitochondrial copper overload in livers of Wilson's disease patients and related animal models

“…This means an efficient removal of excessive copper from mitochondria as early as possible to stop downstream deleterious events. Currently, four copper‐chelating drugs are available to treat WD: British anti‐Lewisite, D‐PA, trientine, and tetrathiomolybdate . Of these, D‐PA and trientine are in clinical use according to current guidelines .…”

Fair pricing of “old” orphan drugs: considerations for Canada’s orphan drug policy

“…In the 1950s and 1960s, dpenicillamine (1956) and trientine (1969) were developed as oral treatments, largely by researchers in the United Kingdom. 3 Now, medical treatment is highly effective in Wilson disease, permitting good health and a normal life span in most patients. 4 However, dpenicillamine causes major adverse effects in 30%-40% of patients with Wilson disease.…”

“…5 Trientine is traditionally the secondline drug used for patients who cannot tolerate dpenicilla mine. Trientine is chemically and mechanisti cally distinct from dpenicillamine, 3 and adverse effects of dpenicillamine typically resolve with trientine treatment. For selected patients, trien tine is the preferred firstline oral chelator.…”