Tiomolibdic acid (trade name Decuprate) is a

chelating agent Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

under investigation for the treatment of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

and of

Wilson's disease Wilson's disease (also called hepatolenticular degeneration) is a genetic disorder characterized by the excess build-up of copper in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, wea ...

, a rare and potentially fatal disease in which the body cannot regulate

copper Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...

. It is developed by

Wilson Therapeutics Wilson Therapeutics is a biopharmaceutical company, based in Stockholm, Sweden, that develops novel therapies for rare diseases. The company is listed in the Mid-Cap segment on Nasdaq Stockholm with the stock ticker WTX. Wilson Therapeutics' lea ...

and used in form of the salt bis-

choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...

tetrathiomolybdate. Wilson's disease is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

genetic disorder that is manifested by serious

hepatic The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

neurologic Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...

or psychiatric symptoms. The disease is fatal if left untreated. It is estimated that 1 individual in every 30,000 to 100,000 worldwide has Wilson's disease. Bis-choline tetrathiomolybdate has been evaluated in

clinical trials Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

in patients with various forms of

and has received orphan designation in the US and EU as a potential therapy against Wilson's disease.

Pharmacology

Mechanism of action

Tiomolibdic acid selectively forms highly stable complexes with copper and proteins. These complexes are then believed to be primarily excreted via the

bile Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...

, restoring the normal excretion route of copper that is impaired in patients with Wilson's disease. The binding and

excretion Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, Kidney (vertebrates), kidneys, and skin. This is in contrast with secretion, where the substa ...

mechanism is stable; whereas many de-coppering agents form unstable complexes that are excreted via urine.

Clinical trials

As of November 2014, a Phase 2, multi-centre, open-label study was 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. As of 2016, tetrathiomolybdate had been tested in over 500 patients for up to seven years, primarily in

oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis, and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's Etymology, etymological origin is the Greek word ὄγ ...

and

, 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.

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 may be helpful 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.

Society and culture

Names

Tiomolibdic acid is the recommended International nonproprietary name (INN).

References

External links

* {{DEFAULTSORT:Tiomolibdic Acid Molybdenum(VI) compounds Orphan drugs Thiometallates