title: Retargeted clostridial neurotoxins as novel agents for treating chronic diseases.
abstract: Botulinum neurotoxin (BoNT) A and B are used to treat neuropathic disorders; if retargeted, these agents could be used to treat medical conditions that involve secretion from nonneuronal cells. Here, we report novel strategies for successfully retargeting BoNTs, and also tetanus neurotoxin (TeNT), to primary human blood monocyte-derived macrophages where BoNT/B inhibited the release of tumor necrosis factor-α, a cytokine that plays a key role in inflammation. Furthermore, mice treated with retargeted BoNT/B exhibited a significant reduction in macrophage (MΦ) recruitment, indicating that these toxins can be used to treat chronic inflammation.
authors: Department of Neuroscience, Howard Hughes Medical Institute, University of Wisconsin, Madison, Wisconsin 53706-1510, United States.
authors: Felix L
authors: FL
authors: Yeh
authors: Yiming
authors: Y
authors: Zhu
authors: William H
authors: WH
authors: Tepp
authors: Eric A
authors: EA
authors: Johnson
authors: Paul J
authors: PJ
authors: Bertics
authors: Edwin R
authors: ER
authors: Chapman
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D002460:Cell Line; D002908:Chronic Disease; D016503:Drug Delivery Systems; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000627:therapeutic use*
chemical_list: D009498:Neurotoxins; D019274:Botulinum Toxins, Type A; C545476:incobotulinumtoxinA