Background: MS is a chronic inflammatory disease of the CNS leading to demyelination
and neurodegeneration, with a complex and still to be clarified aetiology. Several
data, coming from patients' samples and from animal models, show that oxidative status (OS)
plays an important role in MS pathogenesis. Overproduction of reactive oxidative species by
macrophages/microglia can bring about cellular injury and ensuing cell death by oxidizing
cardinal cellular components. Oxidized molecules are present in active MS lesions and are
associated with neurodegeneration.
Methods: We undertook a structured search of bibliographic databases for peer-reviewed research
literature focusing on OS in MS. The contents of the selected papers were described in
the context of a conceptual framework. A special emphasis was given to the results of our
study in the field.
Results: The results of our three recent studies were put in the context and discussed taking
into account the literature on the topic. Oxidative damage underpinned an imbalance shared
by MS and neurodegenerative diseases such as Alzheimer and Parkinson diseases. In people
with clinically isolated syndrome (an early phase of MS) oxidative stress proved to contribute
to disease pathophysiology and to provide biomarkers that may help predict disease evolution.
A drug screening platform based on multiple assays to test the remyelinating potential of library
of approved compounds showed two anti-oxidants, edaravone and 5-methyl-7-
methoxyisoflavone, as active drugs. Moreover, an analysis of 'structure activity relationship'
showed off-targets sites of these compounds that accounted for their remyelinating activity,
irrespective of their antioxidant action.
Conclusion: Overall, edaravone emerges as a candidate to treat complex disease such as MS,
where inflammation, oxidative stress and neurodegeneration contribute to disease progression,
together or individually, in different phases and disease types. Furthermore, approaches based
on drug repositioning seem to maintain the promise of helping discover novel treatment for
complex diseases, where molecular targets are largely unknown.