Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

Expert Rev Clin Pharmacol. 2016 Jun;9(6):755-70. doi: 10.1586/17512433.2016.1172960.


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.

Keywords: Ampligen; Rintatolimod; TLR3 agonist; chronic fatigue/myalgic encephalomyelitis; clinical efficacy; clinical safety; clinical trials; dsRNA; primate/non-primate disassociation of toxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Fatigue Syndrome, Chronic / drug therapy*
  • Fatigue Syndrome, Chronic / physiopathology
  • Humans
  • Immunity, Innate / immunology
  • Poly I-C / adverse effects
  • Poly I-C / pharmacology
  • Poly I-C / therapeutic use*
  • Poly U / adverse effects
  • Poly U / pharmacology
  • Poly U / therapeutic use*
  • RNA, Double-Stranded / metabolism
  • Randomized Controlled Trials as Topic
  • Toll-Like Receptor 3 / agonists*


  • RNA, Double-Stranded
  • Toll-Like Receptor 3
  • Poly U
  • poly(I).poly(c12,U)
  • Poly I-C