Current Biomedical Use of Copper Chelation Therapy Original paper

What was reviewed?

This review explains the current biomedical use of copper chelation therapy across major diseases and ties drug action to copper biology and transport. It summarizes how approved and investigational chelators lower free copper, how zinc limits gut copper uptake, and how these tools fit Wilson’s disease care, neurodegeneration, lung fibrosis, diabetes, and cancer. It also describes why copper balance matters for enzymes, energy use, and redox stress, and how copper transporters like CTR1 and ATP7A/ATP7B affect drug handling and, in cancer, even platinum response. Trials with penicillamine, trientine, tetrathiomolybdate and its bis-choline form, and metal-targeting ionophores appear, with notes on safety and effect. The article closes with how copper lowering can curb tumor vessels, slow spread, and pair with chemo, radiotherapy, and immune drugs.

Who was reviewed?

The review draws on patients with Wilson’s disease, where chelators remove stored copper and zinc maintains low intake; people with Alzheimer’s and Parkinson’s disease from small trials and animal work; adults with idiopathic pulmonary fibrosis tested with tetrathiomolybdate; individuals with diabetes studied for cardiac and metabolic end points; and patients with solid tumors, including breast, ovarian, lung, prostate, and melanoma, in early- and mid-phase trials of copper lowering alone or in combinations. It discusses safety, dose, and limits seen with penicillamine, trientine, ammonium and bis-choline tetrathiomolybdate, DMSA, and metal ionophores such as PBT2, and it notes ongoing or stopped studies that inform today’s practice. It also highlights how copper transport genes may shift drug uptake and resistance in cancer, which links trial design to basic copper handling.

Most important findings

Chelation stands as first-line for Wilson’s disease, with trientine and zinc favored when penicillamine harms or worsens early neuro signs; bis-choline tetrathiomolybdate shows promise for neurologic Wilson’s disease with fewer early setbacks. In Alzheimer’s disease and Parkinson’s disease, results remain mixed and small, which temper the use of outside studies. In lung fibrosis, tetrathiomolybdate lowered fibrotic signals tied to copper-dependent lysyl oxidases. In diabetes, early work with trientine hints at heart benefit, but trials are few. In cancer, copper lowering hits tumor blood growth, matrix cross-linking, spread, and MAPK signaling, and can reduce PD-L1 and raise platinum drug uptake by shifting CTR1 and ATP7A/ATP7B, which may resensitize resistant tumors. Across settings, safety is acceptable with guided copper targets, but long-term balance and patient fit remain key. For microbiome databases, the paper reports no direct taxa shifts; the most relevant markers are host copper status, chelator exposure, and copper-handling genes that frame host–microbe metal stress.

Key implications

Clinicians should match the chelator and goal to the disease stage and watch for copper deficiency, anemia, or immune effects. In Wilson’s disease, plan a de-coppering phase, then maintenance with zinc or trientine. In cancer, consider copper lowering where angiogenesis or MAPK drives growth, or where platinum uptake is poor, and track copper transporters when possible. In lung fibrosis and diabetes, view chelation as an option within trials or niche care until stronger data arrive. For microbiome-aware care, record chelation and copper targets as exposures that can shape host metal pressure on microbes, even if this review gives no taxa signals; this helps interpret culture or sequencing from infected or tumor wounds where metal stress is part of control.