Trade names Decuprate Legal status Investigational PubChem CID 18442052 | ATC code none CAS Number 649749-10-0 Molar mass 432.542 g/mol | |
Synonyms Choline tetrathiomolybdate; ATN-224; WTX101 | ||
Bis-choline tetrathiomolybdate (or tiomolibdate USAN, trade name Decuprate), is a salt of tetrathiomolybdate (TTM, MoS42−) and choline currently under investigation as a therapy against Wilson's disease, a rare and potentially fatal disease in which the body cannot regulate copper. Wilson's disease is an autosomal recessive genetic disorder that is manifested by serious hepatic, neurologic or psychiatric symptoms. The disease is fatal if left undiagnosed and untreated. It is estimated that approximately 1 individual in every 30,000 worldwide have Wilson's disease, corresponding to approximately 15,000 individuals in the European Union and approximately 11,000 in the United States.
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Bis-choline tetrathiomolybdate has been evaluated in clinical trials in patients with various forms of cancer and has received orphan designation in the US and EU as a potential therapy against Wilson's disease.
Bis-choline tetrathiomolybdate is a de-coppering therapy in clinical development against Wilson's disease under the code name WTX101 by Wilson Therapeutics AB. Wilson Therapeutics was founded by HealthCap in 2012.
Mechanism of action
Tetrathiomolybdate has a unique mechanism of action through which it selectively forms highly stable complexes with copper and proteins. These complexes are then believed to be primarily excreted via the bile, restoring the normal excretion route of copper that is impaired in patients with Wilson's disease.
The binding and excretion mechanism of WTX101 is stable; whereas many de-coppering agents form unstable complexes that are excreted via urine.
Clinical trial results and studies in progress
As of 2016, tetrathiomolybdate had been tested in over 500 patients for up to seven years, primarily in oncology and Wilson's disease, as well as some other clinical pathologies.
The data suggest that bis-choline tetrathiomolybdate can rapidly lower and control toxic free copper levels and improve clinical symptoms in Wilson's disease patients. The data also suggest that it is generally well-tolerated with the potential for a reduced risk of neurological worsening after initiation of therapy compared to existing therapies.
As of November 2014, a Phase 2, multi-centre, open-label study is recruiting newly diagnosed Wilson's disease patients 18 and older to evaluate the efficacy and safety of bis-choline tetrathiomolybdate administration over a 24-week period.
Dosing
Previous clinical studies with bis-choline tetrathiomolybdate in oncology patients have shown that it can lower and maintain copper levels using a once or twice daily oral dosing. This is an important finding, since untreated Wilson's disease may lead to death within several years of the onset of symptoms, and medication use should continue throughout the patient's lifespan. Patient compliance is crucial for clinical improvement, and it is a particular challenge for Wilson's disease patients taking de-coppering treatments.