This is a review from Canada telling how iron deposition is part of MS pathophysiology. It suggests that the next generation of iron chelators could be used in controlling toxic iron accumulation. As we know, ATH434 is a next-generation safe iron chelator according to the info we have today. This is just another example of the big potential of ATH434 if the phase 2 study demonstrates efficacy and safety in eliminating iron from the brain.

Review

Mult Scler Relat Disord

. 2023 Aug 9;78:104934.

doi: 10.1016/j.msard.2023.104934. Online ahead of print.

Iron in multiple sclerosis - Neuropathology, immunology, and real-world considerations

Bettina Zierfuss ¹, Zitong Wang ², Alexandra N Jackson ³, Dorsa Moezzi ⁴, V Wee Yong ⁵

Affiliations expand

• PMID: 37579645

DOI: 10.1016/j.msard.2023.104934

Abstract

Iron is an essential element involved in a multitude of bodily processes. It is tightly regulated, as elevated deposition in tissues is associated with diseases such as multiple sclerosis (MS). Iron accumulation in the central nervous system (CNS) of MS patients is linked to neurotoxicity through mechanisms including oxidative stress, glutamate excitotoxicity, misfolding of proteins, and ferroptosis. In the past decade, the combination of MRI and histopathology has enhanced our understanding of iron deposition in MS pathophysiology, including in the pro-inflammatory and neurotoxicity of iron-laden rims of chronic active lesions. In this regard, iron accumulation may not only have an impact on different CNS-resident cells but may also promote the innate and adaptive immune dysfunctions in MS. Although there are discordant results, most studies indicate lower levels of iron but higher amounts of the iron storage molecule ferritin in the circulation of people with MS. Considering the importance of iron, there is a need for evidence-guided recommendation for dietary intake in people living with MS. Potential novel therapeutic approaches include the regulation of iron levels using next generation iron chelators, as well as therapies to interfere with toxic consequences of iron overload including antioxidants in MS.