Anti-snake alpha-neurotoxins antibody: Issues of concern

Snakebites affect between 1.8 to 2.7 million people worldwide each year, being additionally estimated to cause between 80,000 and 138,000 fatalities (1).
Published in Neuroscience and Immunology
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The BMJ
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Anti-snake alfa-neurotoxins antibody: Issues of concern

Dear Editor, As correctly highlighted by Dr Ralph and coworkers in this interesting article, snakebites affect between 1.8 to 2.7 million people worldwide each year, being additionally estimated to cause between 80,000 and 138,000 fatalities (1). Based upon the above, a monoclonal antibody (mAb) targeting and neutralizing the long-chain three-finger alpha-neurotoxins from several snakes has been recently described in another study (2). Should this polyvalent mAb be that effective in humans as it was shown to be in experimentally challenged mice (2), then the authors would deserve highly heartfelt congratulations for a major scientific and humanitarian advance. Nevertheless, the first obvious, self-understandable concern arising from the aforementioned work resides in the objective difficulty to translate tout court to human beings - and, most hopefully, also to domestic and wild animals exposed to snakebite envenomation - the results obtained in the experimental murine model utilized by these investigators (2), given the different susceptibility mice could have, as compared with human and/or other species, to one or more factors of the very complex snake venom’s cocktail, including long-chain three-finger alpha-neurotoxins. Furthermore, although there was obviously a degree of excitement by whomever wrote the aforementioned article (2), little actual detail was included in it, while many future benefits were touted. Within such context, doubts could arise, in fact, following the remark that, although the envenomated mice treated with the anti-alfa-neurotoxin mAb under study lived longer than expected, they still died (2). That claim calls for clarification: Did they all die? How many were in that group? What was the timing from envenomation to death of the mice experimentally challenged with the anti-neurotoxin mAb and controls? In this respect, while it is correctly stated that venom factors other than alfa-neurotoxins could have been responsible for the death of the snake envenom-challenged mice experimentally administered with this anti-neurotoxin mAb (2), the investigators do not provide further details in this direction, which would have been extremely useful. As an additional important remark, while we believe, on one hand, that such an extraordinary post-exposure treatment discovery would definitely deserve our most sincere congratulations, we feel quite surprised, on the other hand, by the fact the investigators did not delve into the multiple species of venomous snakes of tropical South, Central, and North America, where usually pit- and other vipers and coral snakes dominate the envenomating taxa that are responsible for so many snakebite fatalities, as also emphasized in this interesting BMJ article (1).

Based upon the above, a monoclonal antibody (mAb) targeting and neutralizing the long-chain three-finger alpha-neurotoxins from several snakes has been recently described in another study (2).

Should this polyvalent mAb be that effective in humans as it was shown to be in experimentally challenged mice (2), then the authors would deserve highly heartfelt congratulations for a major scientific and humanitarian advance.


Nevertheless, the first obvious, self-understandable concern arising from the aforementioned work resides in the objective difficulty to translate tout court to human beings - and, most hopefully, also to domestic and wild animals exposed to snakebite envenomation - the results obtained in the experimental murine model utilized by these investigators (2), given the different susceptibility mice could have, as compared with human and/or other species, to one or more factors of the very complex snake venom's cocktail, including long-chain three-finger alpha-neurotoxins.


Furthermore, although there was obviously a degree of excitement by whomever wrote the aforementioned article (2), little actual detail was included in it, while many future benefits were touted. Within such context, doubts could arise, in fact, following the remark that, although the envenomated mice treated with the anti-alfa-neurotoxin mAb under study lived longer than expected, they still died (2). That claim calls for clarification: Did they all die? How many were in that group? What was the timing from envenomation to death of the mice experimentally challenged with the anti-neurotoxin mAb and controls?


In this respect, while it is correctly stated that venom factors other than alfa-neurotoxins could have been responsible for the death of the snake envenom-challenged mice experimentally administered with this anti-neurotoxin mAb (2), the investigators do not provide further details in this direction, which would have been extremely useful.


As an additional important remark, while we believe, on one hand, that such an extraordinary post-exposure treatment discovery would definitely deserve our most sincere congratulations, we feel quite surprised, on the other hand, by the fact the investigators did not delve into the multiple species of venomous snakes of tropical South, Central, and North America, where usually pit- and other vipers and coral snakes dominate the envenomating taxa that are responsible for so many snakebite fatalities, as also emphasized in this interesting BMJ article (1).

References

1) Ralph, R., Faiz, M.A., Sharma, S.K., Ribeiro, I., Chappuis, F. (2022). Managing snakebite. BMJ 376: e057926. DOI: 10.1136/bmj-2020-057926.

2) Khalek, I.S., et al. (2024). Synthetic development of a broadly neutralizing antibody against snake venom long-chain alpha-neurotoxins. Science Transl. Med. 16 (735). DOI: https://doi.org/10.1126/scitranslmed.adk1867.

Giovanni Di Guardo
DVM, Dipl. ECVP, Former Professor of General Pathology and Veterinary Pathophysiology, University of Teramo, Veterinary Medical Faculty, Località Piano d’Accio, 64100 Teramo, Italy
Viale Pasteur, 77 - 00144 - EUR - Rome, Italy
 
Fredric L. Frye, DVM, MSc, 
Fellow Royal Society of Medicine, Fellow Federation of Biologists, (Hon.), Dipl. ECVP, (Hon.), Dipl. Am. Acad. Vet. Pathol, Former Professor of Comparative Medicine and Pathobiology, School of Veterinary Medicine, University of California, Davis, California 95616, USA(Email: FredFrye@aol.com)

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