Iron chelation and multiple sclerosis
Open accessAbstract
Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6-8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood-brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.
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Iron deprivation showed some beneficial improvements in MS patients.
“Indeed, iron deprivation reduced EAE, a T cell dependent autoimmune mouse model of MS (Grant et al., 2003) and importantly, showed some beneficial improvements in MS patients (Hametner et al., 2013; Weigel et al., 2014).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Weigel et al., 2014
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Additional file 1 of Iron deposition in multiple sclerosis: overall load or distribution alteration?
Hamdy, E., Galeel, A. A., Ramadan, I., Gaber, D. E., Mustafa, H., & Mekky, J. (2022) · Figshare · doi:10.6084/m9.figshare.21069384
Modulation de l'activation des lymphocytes T et des réponses anti-tumorales par le fer
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Iron overload inhibits neuronal extracellular vesicles secretion via SNARE dysfunction
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Mari, K., Bansari, M., & Memon, B. (2026) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-026-04507-8
- Authors
- Weigel, K. J., Lynch, S. G., & LeVine, S. M.
- Affiliations
- University of Notre Dame (US)
- University of Kansas Medical Center (US)
- Corresponding author
- LeVine, Steven M.
- Venue
- ASN NEURO
- Publisher
- Informa UK Limited
- Published
- 2014-01
- Volume
- 6
- Issue
- 1
- Pages
- e00136-e00136
- ISSN
- 1759-0914 (ISSN-L)
- PMC
- PMC3906635
- OpenAlex
- W2133159465
- Cited by
- 63
- References
- 227
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 6
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ASN NEURO (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (P20GM103418)
- National Center for Research Resources (P20RR016475)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- multiple sclerosis, iron chelation, iron accumulation, deferoxamine, deferasirox, deferiprone, hypoxia-inducible factor-1α, reactive oxygen species, inflammatory cytokines, experimental autoimmune encephalomyelitis, blood-brain barrier
- MeSH terms
- Deferiprone, Animals, Deferoxamine, Humans, Iron, Iron Chelating Agents, Multiple Sclerosis, Pyridones, Chelation Therapy
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