Retargeted Clostridial Neurotoxins as Novel Agents for Treating Chronic Diseases

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), t...

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Bibliographic Details
Published in:Biochemistry (Easton) 2011-12, Vol.50 (48), p.10419-10421
Main Authors: Yeh, Felix L, Zhu, Yiming, Tepp, William H, Johnson, Eric A, Bertics, Paul J, Chapman, Edwin R
Format: Article
Language:English
Subjects:
Animals
Botulinum Toxins, Type A - therapeutic use
Cell Line
Chronic Disease
Drug Delivery Systems
HEK293 Cells
Humans
Inflammation - drug therapy
Inflammation - metabolism
Inflammation - pathology
Macrophages - drug effects
Macrophages - pathology
Macrophages - secretion
Mice
Neurons - drug effects
Neurons - pathology
Neurotoxins - therapeutic use
Rapid Report
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Summary: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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi201490t