Development of WF10, a novel macrophage-regulating agent.
WF10 represents a new class of drug involved in regulating macrophage function both in vitro and in vivo. In the US, WF10 is being evaluated in patients with advanced HIV infection as an adjunct to highly active antiretroviral therapy (HAART). To date, most therapeutic efforts to treat HIV infection have focused on inhibition of viral replication with the goal of decreasing viral load. The introduction of HAART was associated with a dramatic decline in AIDS-related mortality; however, recent indications suggest that the trend maybe changing. WF10, which contains chlorite as the active principle, causes profound changes in macrophage function and activation of gene expression, and appears to downregulate inappropriate immunological activation. The loss of T-cell function observed in HIV-infected patients likely requires the involvement of chronically activated macrophages. Therefore, the persistently activated macrophage represents a therapeutic target that is, unlike HIV, not highly mutable. With this target as a focus, WF10 is being developed for use in advanced HIV disease. WF10 is currently being studied in the US, Europe and Asia for treatment of late-stage HIV disease, as well as recurrent prostate cancer, late post-radiation cystitis, autoimmune disease and chronic active hepatitis C disease.
McGrath
Michael S
MS
AIDS Immunobiology Research Laboratory, San Francisco General Hospital Medical Center, CA 94110, USA. mmcgrath@php.ucsf.edu
Kahn
James O
JO
Herndier
Brian G
BG
D002713:Chlorine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D015870:Gene Expression / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007880:Legislation, Drug; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D010087:Oxides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D014481:United States
D010087:Oxides; D002713:Chlorine; C041955:tetrachlorodecaoxide