Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome.
Latent 2', 5'-oligoadenylate (2-5A) synthetase activity, bioactive 2-5A and RNase L activity were measured in extracts of peripheral blood mononuclear cells (PMBC) before and during a randomized, multicenter, placebo-controlled, double-blind study of poly(I)-poly(C12U) in individuals with chronic fatigue syndrome (CFS) as defined by the Centers for Disease Control and Prevention. The mean values for bioactive 2-5A and RNase L activity were significantly elevated at baseline compared to controls (p < .0001 and p = .001, respectively). In individuals that presented with elevated RNase L activity at baseline, therapy with poly(I)-poly(C12U) resulted in a significant decrease in both bioactive 2-5A and RNase L activity (p = .09 and p = .005, respectively). Decrease in RNase L activity in individuals treated with poly(I)-poly(C12U) correlated with cognitive improvement (p = .007). Poly(I)-poly(C12U) therapy resulted in a significant decrease in bioactive 2-5A and RNase L activity in agreement with clinical and neuropsychological improvements (Strayer DR, et al., Clin. Infectious Dis. 18:588-595, 1994). The results described show that poly(I)-poly(C12U) is a biologically active drug in CFS.
Suhadolnik
R J
RJ
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Reichenbach
N L
NL
Hitzges
P
P
Adelson
M E
ME
Peterson
D L
DL
Cheney
P
P
Salvato
P
P
Thompson
C
C
Loveless
M
M
Müller
W E
WE
D015088:2',5'-Oligoadenylate Synthetase / Q000502:physiology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004722:Endoribonucleases / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy*; D006801:Humans; D011070:Poly I-C / Q000627:therapeutic use*; D011072:Poly U / Q000627:therapeutic use*; D012330:RNA, Double-Stranded / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D012330:RNA, Double-Stranded; D011072:Poly U; C047490:poly(I).poly(c12,U); D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D011070:Poly I-C