A Controlled Clinical Trial with a Specifically Configured RNA Drug, Poly(I). POly(C12U), in Chronic Fatigue Syndrome

Abstract

Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition. In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined. Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance. After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).

Generation of mature dendritic cells fully capable of T helper type 1 polarization using OK‐432 combined with prostaglandin E2

“…8) Multiple reagents have been reported to induce DC maturation. The known DC maturation stimuli include CD40 ligand (CD40L), 4,9,10) poly I:C (a synthetic double-stranded RNA), 11,12) interferon (IFN)-α, lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, and conditioned medium of adherent autologous monocytes in culture, termed monocyte-conditioned medium (MCM). Among these currently available reagents, MCM has been considered to be one of the best stimuli.…”

Single-Blind, Placebo Phase-in Trial of Two Escalating Doses of Selegiline in the Chronic Fatigue Syndrome

“…That interpretation is important in that CFS is a disabling illness with limited treatment options primarily directed toward symptom relief; in fact, the one drug with a specific indication for treating CFS [17] -poly(I)Wpoly(C 12 U) -is not approved in many countries for use. However, the lack of a placebo control group in our study allows for other interpretations.…”

Dual Role of TLR3 in Inflammation and Cancer Cell Apoptosis

“…Poly(I:C12U) is a GMP-grade molecule that, in contrast to Poly-ICLC, undergoes accelerated hydrolysis because of regular regions of mismatching. However, Poly(I:C12U) maintains pharmacological activity [92]. Poly-ICLC remains toxic -notably with doses greater than 12 mg/m2 -whereas Poly(I:C12U) showed no evidence of dose-limiting organ toxicity.…”

“…Poly-ICLC remains toxic -notably with doses greater than 12 mg/m2 -whereas Poly(I:C12U) showed no evidence of dose-limiting organ toxicity. Indeed, Poly(I:C12U) has been previously tested in the treatment for chronic fatigue syndrome and AIDS without apparent toxicity [92]. Moreover, Poly(I:C12U) is shown to specifically target TLR3 [93].…”