Snakebite treatment hope after drug combination success

New drug combinations could protect snakebite victims from life-changing injuries caused by toxic venom.

Promising new research led by a team at the Centre for Snakebite Research & Interventions (CSRI) at Liverpool School of Tropical Medicine, UK, suggests combining repurposed small molecule drugs could inhibit specific snake venom toxins.

These could be deployed quickly in the field immediately following a snakebite, possibly averting devastating injuries.

Existing antivenom treatments are largely ineffective against the tissue destruction caused by the cytotoxic venomous bites of different snake species. It is given intravenously when a patient arrives at hospital, at which point much of the irreversible tissue damage has been done.

In this study, the team found combining repurposed small molecule drugs were effective against several snakes with drastically different venom toxin profiles. This has raised the hope that it could lead to an effective future pan-species, pan-continental snakebite therapy.

Professor Nicholas Casewell, head of CSRI at LSTM, said: “Our findings are exciting because they show that combinations of drugs that have already been shown to be safe in human clinical trials can prevent local tissue damage caused by different snake species. This is important because cytotoxic snake venoms cause hundreds of thousands of cases of morbidity each year across the world. Identifying new, affordable and safer treatments for snakebite is a priority to mitigate the devastating impact caused by this neglected tropical disease”.

Lead researcher Dr Steven Hall, previously of LSTM and now at Lancaster University, analysed repurposed the small molecule drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat and varespladib, which target different toxins found in snake venoms.

In preclinical studies using human skin cells and animal models, rationally designed combinations of these three drugs protected against the necrotic effects of venoms from genetically and geographically diverse medically important snake species – something that current antivenom treatments cannot do.

Although more work is needed before these drug combinations are used in snakebite patients, the researchers hope that these findings will accelerate support for their onward development into clinical trials.

Dr Hall said: “Snakebite affects millions of people yearly with upwards of 400,000 being permanently injured as a result, which is why this study is so promising. We successfully showed that combining two drugs that target just two different snake venom toxin families can almost completely inhibit the skin necrotising activity of a wide range of geographically distinct snake species with differing venom profiles. Even more impressive is the fact that this reduction in necrosis remained significant even when the drugs were administered up to an hour after the envenoming event in vivo”.

Hall SR, Rasmussen SA, Crittenden E et al. Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms. Nature Communications 14 December 2023; doi: 10.1038/s41467-023-43510-w

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