Inorganic elements, such as copper, zinc and iron, are vital to the healthy functioning of all cells in living organisms. But they are high-maintenance nutrients, and too much can be toxic, as is the case in Wilson disease, a genetic disorder that prevents the body from getting rid of extra copper and leads to liver and neurological problems.

Copper also is an important cofactor for tumor angiogenesis, the process of growing new blood vessels to feed the tumor. Researchers believe this is why tetrathiomolybdate has shown promise as an anti-cancer drug.

The chain of discovery that led to the use of tetrathiomolybdate as a therapeutic agent began in the 1930s when cows grazing in certain types of pastures in England developed neurological problems. This trouble was then linked to other neurological problems with sheep grazing on certain soils in Australia. It was found that molybdate, a non-toxic compound present in the grass of these pastures, when consumed in excessive amounts by the ruminants, led to copper deficiencies and neurological problems in the animals.

As copper overload disorders such as Wilson disease were discovered in humans, physicians used molybdenum chemistry focusing on tetrathiomolybdate to lower copper levels in the body. (Tetrathiomolybdate is an inorganic small molecule first synthesized by J. J. Berzelius in 1826.)

Tetrathiomolybdate is the active pharmaceutical agent in a well-tolerated drug that has shown activity for the treatment of Wilson disease and now is in phase II clinical trials as an anti-cancer drug.

TM also has been examined in recent studies where copper dysregulation is implicated in the pathogenesis of neurodegenerative diseases such as familial amyotrophic lateral sclerosis (ALS), Parkinson's disease, multiple sclerosis and Alzheimer's disease as well as primary pulmonary hypertension and left ventricular hypertrophy associated with type II diabetes. Copper modulating agents including TM have been shown to be active in animal models of these diseases providing a rationale for advancing tetrathiomolybdates into clinical evaluation in these areas.

Source: Northwestern University