Hi, Tom - Coincidentally, I did a search on WF10, there, last night. No big surprises; list follows:
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Infection 1998 Jul-Aug;26(4):202-7 (ISSN: 0300-8126)
Raffanti SP; Schaffner W; Federspiel CF; Blackwell RB; Ching OA; Kuhne FW
Dept. of Medicine, Vanderbilt School of Medicine, Nashville, TN 37232-2637, USA.
A randomized, double-blind trial compared treatment with the immune modulator WF10 (ten patients) and placebo (nine patients) administered in cycles over 3 months among individuals with advanced AIDS. There were no notable clinical adverse events; changes in hematologic and chemistry values were comparable in the two groups. In both groups, median HIV-RNA PCR values remained stable. Immunologic variables showed a consistent tendency to increase in the WF10 group and to decrease in the control group, with significant differences between groups for median WBC, lymphocyte, CD19, and CD35 values.
Ten infections occurred in the control group, four of which were Pneumocystis carinii pneumonia (PCP), and three in the
WF10 group none of which was PCP. Five patients in the control group were hospitalized during the trial for a total of 53 days; no patients in the WF10 group were hospitalized. Over a subsequent 9-months follow-up, six patients from the control group and one from the WF10 group died. These results indicate that WF10 administration appears safe, may enhance immunologic function, and unlike other macrophage-activating cytokines does not increase HIV expression in this patient population. Further studies of WF10 in larger patient populations are warranted.
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Pharmacol Toxicol 2001 Aug;89(2):92-5 (ISSN: 0901-9928)
Hansen A; Kemp K; Kemp E; Bouchelouche K; Bouchelouche P; Dieperink H; Horn T; Larsen S
Department of Pathology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. alha@herlevhosp.kbhamt.dk.
WF10 is a stabilized chlorite matrix with immunosuppressive effects. In vitro studies have demonstrated its ability to
suppress T cells and delay or abolish antigen presentation. Hence, WF10 may prove useful to prolong graft survival after transplantation. In this study, we evaluated the use of high dose WF10 as a single drug regimen in the hamster-to-rat xenotransplantation model and searched for possible cardiotoxic side effects. WF10 prolonged cardiac xenograft survival, but did not induce tolerence or inhibit pathological signs of acute rejection. Hamsters from the donor population, receiving high dose WF10 for 5 days, were compared with a matched control group. Ultrastructural examination of cardiac tissue as well as biochemical analysis of the cardiac enzymes troponin I, myoglobin and MB isoenzyme of creatine kinase showed no signs of damage. Thus, while prolonging graft survival, high dose WF10 seems to be non-cardiotoxic and as such should not contribute to the differential diagnosis of acute graft failure
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Arzneimittelforschung 2001;51(7):554-62 (ISSN: 0004-4172)
Schempp H; Reim M; Dornisch K; Elstner EF
Institute of Phytopathology, Technical University Munich, Freising, Germany. h.schempp@flg.tum.de.
WF10 is a chlorite-based drug that modulates macrophages functional states and can be safely administered to humans.
WF10 potentially modulates disease-related up-regulation of immune responses both in vitro and in vivo. Thus immune response is influenced in a way that inappropriate inflammatory reactions are downregulated. The molecular mechanisms involved are not completely understood. Biochemical data suggest the reaction of chlorite with hemoproteins as the central step in the activation process of the drug. Thereby a chlorinating agent is generated, resulting in the oxidation of reduced sulfur-containing molecules and in the conversion of amino residues into more or less stable chloramines.
The most prominent chloramine in vivo is taurine chloramine. Taurine chloramine is a long-lived molecule with immunomodulatory properties. For instance, taurine chloramine inhibits the generation of macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). This study on the biochemical mechanism of WF10 gives evidence that hemoprotein dependent chlorination of taurine is not only observed in vitro but also very likely in vivo. To characterize the oxidant, generated during heme activation, different methods were used: Chemiluminescence, EPR-spectroscopy, UV/VIS-spectroscopy, gas (GC) and size exclusion chromatography. In summary, the results indicate as the first products of hemoprotein catalyzed chlorite activation a chloroxygen-species (probably HOCl/OCl-) and a ferryl-oxygen species at the hemoprotein active site in analogy to the known peroxidase (compound I and II) intermediates. Moreover, hydrogen peroxide and chlorite seem to react in a similar way with heme centers. It is proposed that WF10 represents an "inactive" transport form of potentially active chlorine. Reactivity of the latter is restricted unless heme moieties in proteins or enzymes activate he "transport form" to perform reactions in analogy to peroxidases (i.e. myeloperoxidase-catalyzed formation of HOCl/OCl
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McGrath MS; Kodelja V
University of California, San Francisco, Calif., USA.
Macrophages play a central role in the immune response and are major targets for chronic infection with viruses such as HIV.
Recent studies on macrophage differentiation have shown the existence of classical activation and the counter-balancing
anti-inflammatory alternative activation states. In the 'balanced macrophage activation hypothesis' we propose that macrophage activation is a cyclic process that balances these two states to achieve proper immunologic function.
Dysregulation of this cycle would, therefore, be associated with various forms of chronic disease. This model has been
utilized in the drug development of WF10, a novel macrophage-targeted drug, currently in advanced clinical testing for the treatment of HIV disease. [Copyright 2000 S. Karger AG, Basel |
