Tiomolibdic acid (trade name Decuprate) is a

chelating agent Chelation is a type of bonding of ions and 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 ligands are ...

under investigation for the treatment of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

and of

Wilson's disease Wilson's disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, ...

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

copper Copper is a chemical element with the symbol Cu (from la, cuprum) 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 pinkis ...

. 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 an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but re ...

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 effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic disorder that is manifested by serious

hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

neurologic Neurology (from el, νεῦρον (neûron), "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 brain, the spinal c ...

psychiatric symptoms A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...

. The disease is fatal if left untreated. It is estimated that approximately 1 individual in every 30,000 worldwide has Wilson's disease, corresponding to approximately 15,000 individuals in the European Union and approximately 11,000 in the United States. Bis-choline tetrathiomolybdate has been evaluated in

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

in patients with various forms of

and has received

orphan designation An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

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''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...

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

excretion Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...

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 etymological origin is the Greek word ὄγκος (''ó ...

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