A Toll-Like Receptor 3-Agonist as Promising Candidate in Multiple Sclerosis Treatment

Perturbations in immune processes play an important role in multiple sclerosis (MS), an autoimmune disorder where specific innate immune pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs) have recently been shown to play a major role in the initiation disease, the triggering of relapses, and regulation of CNS damage. The abnormal immune response in MS has been shown to be dependent on genetic background, despite environmental factors, including pathogens capable of overstimulating innate immune response through TLRs, appear to contribute to the development of autoreactive T cells that in turn cause myelin damage. However, whereas the upregulation of most TLRs plays a detrimental role in MS pathogenesis, recent studies suggest an ameliorative role of TLR3 in the onset and progression of MS and experimental autoimmune encephalomyelitis (EAE), a murine model of MS. TLR3 activation appears to protect from the disease, mainly through induction of interferon (IFN)β. Therefore, TLR3 stimulation with synthetic immunomodulators could represent a potential alternative approach in MS therapy. Among the investigational compounds TLR3-targeting, the mismatched double-stranded RNA molecule Ampligen®, can offer promise in the treatment of relapsing MS patients. Ampligen® is currently in phase III clinical trial in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), an illness that shows remarkable levels of similarity with MS. The aim of this paper is to provide a brief overview about Ampligen® historical development, clinical pharmacology, clinical trials, and safety data, and to discuss about its potential role in MS treatment in the context of existing therapeutic options.