Every year, venomous snakebite affects more than 2 million people and causes an estimated 138,000 deaths. It is also responsible for two to three times as many permanent disabilities and in 2017 the World Health Organisation finally designated venomous snakebite as a category A neglected tropical disease. Currently the only specific treatment for snakebite is antivenom but this has many limitations, including a high production cost, low affordability, the need to be kept refrigerated and the need to be administered in a hospital due to the high risk of anaphylaxis. A new study by Albulescu et al. (2020) however, suggests that a drug originally used for heavy metal poisoning could be repurposed to help in the treatment of bites by some species of viper.
Viper venom is often described as being haemotoxic, containing various components which affect blood clotting, blood pressure and cause local or systemic haemorrhaging. Some of these components known as zinc-dependent snake venom metalloproteinases (SVMPs), appear to be inhibited by the repurposed drugs Dimercaprol, 2,3- dimercapto-1-propanesulfonic acid (DMPS), and dimercaptosuccinic acid (DMSA). In vitro studies showed that these drugs inhibited SVMP activity in venoms from six medically important sawscaled vipers (genus Echis); a small but deadly group of snakes that are distributed across Africa, the Middle East, and South Asia. A study in mice also showed that DMPS almost completely prevented the haemorrhagic skin lesions associated with Echis ocellatus envenomation. DMPS, given 15 minutes after envenomation also improved survival when antivenom was administered 45 minutes after DMPS.
In a real-life scenario, this may mean that DMPS could be used as a first-line treatment before receiving antivenom in hospital. Taken quickly after a viper bite it could limit localised tissue damage, which usually occurs within the first few minutes after a bite. DMPS has a proven safety profile, is low cost and can be taken orally, making it a practical drug for self-administration in areas where vipers are endemic. The study highlights that despite snakebite being a serious medical emergency, DMPS might create a false sense of security among victims or medical practitioners, meaning that the administration of antivenom may be delayed. This can be overcome by developing proper clinical guidelines through a clinical trial.
Further pre-clinical studies now need to be conducted to test the efficacy and safety of DMPS against a range of viper venoms and should the drug be deemed an effective treatment, the fact that it is already licensed will help to speed up the clinical trial stage.
You can read the original research article at the Science of Translational Medicine.
L.-O. Albulescu, M. S. Hale, S. Ainsworth, J. Alsolaiss, E. Crittenden, J. J. Calvete, C. Evans, M. C. Wilkinson, R. A. Harrison, J. Kool, N. R. Casewell (2020). Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite. Sci. Transl. Med. 12. Issue 542.
C. Y. Koh, R. Bendre, R. M. Kini (2020). Repurposed drug to the rescue of snakebite victims. Sci. Transl. Med. 12, eabb6700.