The conundrum of iron in multiple sclerosis – time for an individualised approach

Susan J Van Rensburg,Maritha J Kotze,Ronald Van Toorn

doi:10.1007/s11011-012-9290-1

Susan J Van Rensburg, Maritha J Kotze + Show 1 more

Open Access

https://doi.org/10.1007/s11011-012-9290-1

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Abstract

Although the involvement of immune mechanisms in multiple sclerosis (MS) is undisputed, some argue that there is insufficient evidence to support the hypothesis that MS is an autoimmune disease, and that the difference between immune- and autoimmune disease mechanisms has yet to be clearly delineated. Uncertainties surrounding MS disease pathogenesis and the modest efficacy of currently used disease modifying treatments (DMTs) in the prevention of disability, warrant the need to explore other possibilities. It is evident from the literature that people diagnosed with MS differ widely in symptoms and clinical outcome - some patients have a benign disease course over many years without requiring any DMTs. Attempting to include all patients into a single entity is an oversimplification and may obscure important observations with therapeutic consequences. In this review we advocate an individualised approach named Pathology Supported Genetic Testing (PSGT), in which genetic tests are combined with biochemical measurements in order to identify subgroups of patients requiring different treatments. Iron dysregulation in MS is used as an example of how this approach may benefit patients. The theory that iron deposition in the brain contributes to MS pathogenesis has caused uncertainty among patients as to whether they should avoid iron. However, the fact that a subgroup of people diagnosed with MS show clinical improvement when they are on iron supplementation emphasises the importance of individualised therapy, based on genetic and biochemical determinations.

Highlights

Whether iron supplementation is beneficial or harmful to people with multiple sclerosis (MS) has been debated for several years
Over the last 15 years our research has identified a subgroup of patients who, having presented with low iron parameters at diagnosis, subsequently followed a benign disease course only when the iron deficiency was alleviated through continuous lifelong supplementation (Kotze and Rooney 1997; Rooney et al 1999; Kotze et al 2001; van Rensburg et al 2006; van Toorn et al 2010)
Contrary to the belief that iron is harmful and invariably causes oxidative damage, it may paradoxically represent the key component of the entire antioxidant protection system of the oligodendrocyte, since: (1) Iron is required for the production of ATP, which is essential for the synthesis of NADPH, the reducing power of the cell

Summary

Introduction

Whether iron supplementation is beneficial or harmful to people with multiple sclerosis (MS) has been debated for several years. The autoimmune hypothesis, based to a large extent on results obtained with EAE, states that potentially autoaggressive T cells exist in the blood of patients with MS, having been activated by an antigen that mimics myelin proteins.

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Conclusion