English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/216226
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Preclinical Validation of a Repurposed Metal Chelator as an Early-Intervention Therapeutic for Hemotoxic Snakebite

AuthorsAlbulescu, Laura-Oana; Hale, Melissa S.; Ainsworth, Stuart; Alsolaiss, Jaffer; Crittenden, Edouard; Calvete, Juan J. ; Evans, Chloe; Wilkinson, Mark C.; Harrison, Robert A.; Kool, Jeroen; Casewell, Nicholas R.
Issue Date6-May-2020
PublisherAmerican Association for the Advancement of Science
CitationScience Translational Medicine 12(542):eaay8314 (2020)
AbstractSnakebite envenoming causes 138,000 deaths annually, and ~400,000 victims are left with permanent disabilities. Envenoming by saw-scaled vipers (Viperidae: Echis) leads to systemic hemorrhage and coagulopathy and represents a major cause of snakebite mortality and morbidity in Africa and Asia. The only specific treatment for snakebite, antivenom, has poor specificity and low affordability and must be administered in clinical settings because of its intravenous delivery and high rates of adverse reactions. This requirement results in major treatment delays in resource-poor regions and substantially affects patient outcomes after envenoming. Here, we investigated the value of metal ion chelators as prehospital therapeutics for snakebite. Among the tested chelators, dimercaprol (British anti-Lewisite) and its derivative 2,3-dimercapto-1-propanesulfonic acid (DMPS) were found to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also considerably extended survival in a "challenge and treat" model, where drug administration was delayed after venom injection and the oral administration of this chelator provided partial protection against envenoming. Last, the potential clinical scenario of early oral DMPS therapy combined with a delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. Our findings demonstrate that the safe and affordable repurposed metal chelator DMPS can effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the promise of this drug as an early, prehospital, therapeutic intervention for hemotoxic snakebite envenoming.
DescriptionVersión preprint: 40 páginas 7 figuras y material suplementario.
Publisher version (URL)http://dx.doi.org/10.1126/scitranslmed.aay8314
URIhttp://hdl.handle.net/10261/216226
DOIhttp://dx.doi.org/10.1126/scitranslmed.aay8314
ISSN1946-6234
E-ISSN1946-6242
Appears in Collections:(IBV) Artículos
Files in This Item:
File Description SizeFormat 
2020 Sci Transl Med 12-eaay8314 Preprint.pdf901,5 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.