Abstract
There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.
Highlights
Snakebite envenoming is a threat to more than five billion people and at least 750 million who live more than 1 h from a health care facility [1]
In the last two years has snakebite received recognition as a Neglected Tropical Disease; Fayrer0 s words are as relevant today as they were more than a century ago [3,5]
The definitive treatment for snakebite envenoming requires the intravenous administration of animal-derived antivenoms at a health care facility [3,6]
Summary
Snakebite envenoming is a threat to more than five billion people and at least 750 million who live more than 1 h from a health care facility [1]. Snakebite envenoming kills 81,000–138,000 people annually and leaves hundreds of thousands with amputations, disfiguring injuries, and both chronic physical and psychological sequelae [3,4]. In the last two years has snakebite received recognition as a Neglected Tropical Disease; Fayrer0 s words are as relevant today as they were more than a century ago [3,5]. The definitive treatment for snakebite envenoming requires the intravenous administration of animal-derived antivenoms at a health care facility [3,6]. More than 75% of deaths from snakebite envenoming occur before reaching hospital care [1,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
