Disease relevance of Ampligen

• Thus, in the short term, ampligen seems to have the dual ability to restore immunological function and to control HIV replication [1].
• Thus, combined therapy with ampligen and AZT can be expected to be more beneficial than AZT alone to patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex since AZT regimens that seem to be clinically effective are associated with considerable toxicity [2].
• Clinical, immunological, and virological effects of ampligen, a mismatched double-stranded RNA, in patients with AIDS or AIDS-related complex [1].
• We evaluated the efficacy of the interferon inducer Ampligen on coxsackie B3 virus-induced myocarditis in C3H/HeNHsd mice [3].
• We evaluated the prophylactic and therapeutic efficacy of interferon alpha-2b, pegylated interferon alpha-2b, poly(I. C), and Ampligen against Modoc virus encephalitis in an animal model for flavivirus infections [4].

High impact information on Ampligen

• Mismatched double-stranded RNA (ampligen) reduces concentration of zidovudine (azidothymidine) required for in-vitro inhibition of human immunodeficiency virus [2].
• As a first step in determining the molecular events responsible for growth arrest, we have explored the role of signal transduction through the cAMP system in the antiproliferative effect of the mismatched dsRNA, r(I)n.r(C12,U)n (Ampligen) [5].
• The growth of the xenografts was inhibited by beta-interferon (IFN-beta), polyriboinosinic acid.polyribocytidilic acid, the mismatched double-stranded RNA analogue r(I)n . r(C12,U)n, and to a lesser extent recombinant IFN-beta, when treatment was initiated at the time of tumor inoculation [6].
• Despite the observed advantages of interferon alfacon-1 therapy, efforts to stimulate the immune system with the known interferon inducer poly(I:C12U) (Ampligen) offered only limited protection against lethal PCV challenge [7].
• Ampligen at 20 mg/kg of body weight/day was able to reduce the severity of virus-induced myocarditis, as assessed by morphometric analysis, by 98% (P = 3.0 x 10(-8)) [3].

Chemical compound and disease context of Ampligen

• The results of this study indicate that Ampligen can significantly reduce the bleomycin-induced increased collagen accumulation and may be therapeutically useful in the management of lung fibrosis in humans [8].
• In the present report we examined three agents in the Rauscher retrovirus model: imexon, Ampligen and poly[I,C]-LC [9].
• The use of ampligen alone and in combination with ganciclovir and coumermycin A1 for the treatment of ducks congenitally-infected with duck hepatitis B virus [10].
• Treatment of lethal Pichinde virus infections in weanling LVG/Lak hamsters with ribavirin, ribamidine, selenazofurin, and ampligen [11].
• Mismatched double-stranded RNA of the form r(I)n.r(C12-U)n (Ampligen) has been shown to be active against human immunodeficiency virus type 1 (HIV-1) using CEM and C3 cells as targets for infection by the highly similar HIV-1 isolates HTLV-IIIB and LAV (Montefiori, D.C. and Mitchell, W.M., 1987, Proc. Natl. Acad. Sci. U.S.A., 84, 2985-2989) [12].

Biological context of Ampligen

• In addition, there was a significant increase in CD4+ cell counts with respect to dose of ampligen [13].
• The unique properties of Ampligen which support this hypothesis include activation of immune cells, inhibition of virus replication by inducing an antiviral cellular state and inhibition of growth of neoplastic cells [14].
• Poly(rI:rC) and Ampligen were entrapped in liposomes that were covalently coupled to Protein A, permitting binding to antibodies specific for the major histocompatibility complex-encoded H2K molecule of L929 cells, or to control antibodies [15].

Anatomical context of Ampligen

• In all cell lines, a synergistic antiproliferative effect was seen with all IFN preparations studied in combination with Ampligen, as calculated by the isobole method according to Berenbaum (1981) [16].
• Four human tumor cell lines were studied for their response to antiproliferative effects of various interferons (IFNs) alone and in combination with the novel mismatched dsRNA, r(I)n r(C12,U)n (Ampligen) [16].
• Preliminary in vitro data have demonstrated that a novel clinically non-toxic analogue polymer poly [I]:poly [C(12)U] (Ampligen R) can effectively induce in vitro maturation of human monocyte derived DC with sustained bioactive IL12 production [17].
• Lymphokine-activated killer (LAK) cell activity was measured in human peripheral blood mononuclear cells (PBMC) treated in vitro for 3 days with recombinant interleukin-2 (rIL-2) and mismatched double-stranded RNA (dsRNA) [18].
• Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R) [17].

Associations of Ampligen with other chemical compounds

• The second half-life is significantly longer than a variety of nucleic acids such as poly-IC and Ampligen and suggests therapy with phosphorothioate oligonucleotides should be possible and practical [19].
• 2',5'-Oligoadenylate synthetase was induced 3-2000-fold in spleen, liver, kidney and brain of NIH Swiss mice injected intravenously with 2-200 micrograms of the misaligned dsRNA, poly(I).poly(C12,U) [20].
• Synergism was also found between ampligen and zidovudine by reduction of HIV-produced plaques in a HeLa cell line expressing CD-4 receptors [21].
• Animals receiving bleomycin plus Ampligen at all dosages had significantly reduced prolyl hydroxylase activity compared to the bleomycin control group [8].
• Intraperitoneal selenazofurin (1-100 mg/kg per day for 10 days) and ampligen (0.5 and 5 mg/kg every other day for 5 injections) treatments provided neither protection from the lethal infection nor increased mean survival times [11].

Gene context of Ampligen

• DC maturation can be achieved with Toll-like receptor (TLR) agonists, such as the GMP-grade synthetic double stranded RNA, poly[I]:poly[C12U] (Ampligen) which is a TLR-3 agonist [22].
• Potentiated lymphokine-activated killer cell activity generated by low-dose interleukin-2 and mismatched double-stranded RNA [18].
• These results indicate that IFN-alpha and IFN-beta alone or combinations of type I IFNs, type II IFNs and Ampligen can be effective in inhibiting the growth of glioma cells [23].
• The immunomodulatory effects of Ampligen are manifested as a stabilization of CD4 counts [24].
• This Caraparu disease model was relatively resistant to treatment with immunomodulators, such as ABMP, Ampligen, alpha-interferon (IFN-alpha) or beta-interferon (IFN-beta) [25].

Analytical, diagnostic and therapeutic context of Ampligen

• The observed efficacies of Ampligen and poly(IC) were corroborated by the observation that the drugs also markedly reduced the virus titers in the heart, as detected by (i) quantitative real-time reverse transcription-PCR and (ii) titration for infectious virus content [3].
• Viral load (as measured on day 7 postinfection) was significantly reduced by 80 to 100% in the serum, brain, and spleen in mice that had been treated with either interferon alpha-2b, pegylated interferon alpha-2b, poly(I. C), or Ampligen [4].
• Detection of poly(I):poly(C12U), mismatched double-stranded RNA, by rapid solution hybridization: blood values after intravenous infusion [26].
• In crosslinking and immunoprecipitation experiments we present evidence that 2-5A (32P-labelled 2-5A derivative, ppp(A2'p)3 A[32P]pCp) is able to bind to nuclear topoisomerase I. The mismatched dsRNA, poly(I).poly(C12U) (Ampligen), exhibited a strong anti-HIV-1 activity [27].
• Intraperitoneal injection of IFN-alpha B/D (qd for 7 days), polyI-polyC(12)U [Ampligen (every other day for 7 days)] and topically applied imiquimod (qd for 7 days), administered from 1 day before viral challenge, were effective in protecting, respectively, 100%, 100% and 70% of BALB/c mice from mortality induced by subcutaneous injection of WNV [28].

References