title: Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).
abstract: Chronic fatigue syndrome/ Myalgic encephalomyelitis (CFS/ME) is a poorly understood seriously debilitating disorder in which disabling fatigue is an universal symptom in combination with a variety of variable symptoms. The only drug in advanced clinical development is rintatolimod, a mismatched double stranded polymer of RNA (dsRNA). Rintatolimod is a restricted Toll-Like Receptor 3 (TLR3) agonist lacking activation of other primary cellular inducers of innate immunity (e.g.- cytosolic helicases). Rintatolimod also activates interferon induced proteins that require dsRNA for activity (e.g.- 2'-5' adenylate synthetase, protein kinase R). Rintatolimod has achieved statistically significant improvements in primary endpoints in Phase II and Phase III double-blind, randomized, placebo-controlled clinical trials with a generally well tolerated safety profile and supported by open-label trials in the United States and Europe. The chemistry, mechanism of action, clinical trial data, and current regulatory status of rintatolimod for CFS/ME including current evidence for etiology of the syndrome are reviewed.
authors.affiliation: a Department of Pathology, Microbiology & Immunology , Vanderbilt University , Nashville , USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D011070:Poly I-C / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011072:Poly U / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012330:RNA, Double-Stranded / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D051196:Toll-Like Receptor 3 / Q000819:agonists*
chemical_list: D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C
keywords: Ampligen; Rintatolimod; TLR3 agonist; chronic fatigue/myalgic encephalomyelitis; clinical efficacy; clinical safety; clinical trials; dsRNA; primate/non-primate disassociation of toxicity