The Iron Paradox: Chelation Therapy’s Impact on Parkinson’s

For decades, researchers long assumed that excessive iron accumulation in the substantia nigra contributed to the neurodegeneration in Parkinson’s Disease based on elevated iron levels found in post-mortem, MRI studies of patients and the discovery of ferroptosis, an iron-dependent form of cell death, introducing Chelation therapy (the process of removing heavy metals from the body) as a potential treatment for Parkinson’s patients. 

However, a paper recently published by Ian Peikon and Nancy C. Andrews challenges that assumption. In the latest edition of The Journal of Clinical Investigation, researchers point out that multiple clinical trials using a drug called Deferiprone (a brain-penetrant iron chelator) had the opposite effect on patients, making their motor symptoms worse, especially with newly diagnosed and drug-naive patients. These outcomes directly contradict the iron-overload hypothesis and suggest that iron removal could be depriving neurons of something essential. Bioavailable iron (the iron absorbed by the body from foods) is essential for dopamine synthesis and mitochondrial respiration, which are both impaired functions of the brain as a result of Parkinson’s taking hold.

Researches suggest that neurons may be “iron-starved,” despite MRI imaging suggesting that there may be an overabundance. “Though it may appear that patient brains are overloaded with iron, the data are equally consistent with a functional iron deficiency of the dopaminergic neurons.” state the authors of the paper, “While the total amount of iron in the tissue may be normal or elevated, bioavailable Fe²+ in the dopaminergic neurons is low due to sequestration in subcellular compartments or nearby cells.”

Researchers also point to studies of people with manganism, a neurological disorder caused by excessive manganese exposure from sources such as mining, battery manufacturing, or contaminated water, which show Parkinson’s-like symptoms driven by disrupted cellular iron balance and an iron-deficient state. 

The authors make the argument that Iron chelation in Parkinson’s Disease has been thoroughly tested and fails to provide benefits in treating the disease, and removing iron from the body makes symptoms worse. Instead, the point out the focus should be on restoring iron bioavailability by targeting iron trafficking to restore dopamine production and improving access to usable iron, rather than focusing on how much iron exists. 

The entire paper can be read here.

_{^{Unless noted, all media by Chris Denny}}