Jornal de Ensaios Clínicos
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A New Era for Immunotherapeutic Approaches in Multiple Sclerosis Treatment

Maria Elsa Gambuzza, Luca Soraci, Vincenza Sofo, Silvia Marino and Placido Bramanti

Recent studies have shown that many pathological conditions, including neurodegenerative disorders, are always the result of innate immune dysregulations. In multiple sclerosis (MS), innate immunity has shown induce proinflammatory responses, mainly mediated by specific innate immune receptors, as well as Toll-like receptors (TLRs). Interestingly, whereas activation of TLR-MyD88 dependent signaling pathway induces inflammation and MS progression, TLR3 activation MyD88 independent seems to play a beneficial effect, probably due to its ability to enhance endogenous IFN-β production, that in turn down regulates proinflammatory responses. Consequently, new therapeutic approaches based on TLR up and/or down regulation could offer promising results. In addition to several classes of TLR antagonists represented by different types of antibodies, nanobodies, mimetic molecules and RNAselective interference compounds, TLR3 agonists appear particularly interesting due to their capability of inducing IFN-β production. Among these, Ampligen® shows early promise, since it has shown positive results in several phase III trials for the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), an illness that shows remarkable levels of similarity with MS.