Researchers at LSTM & VU demonstrate a novel way to treat snakebite by combining small molecule inhibitor drugs as repurposing treatment candidates

The Research has been published in Nature Communications

12/21/2020 | 10:09 AM

A paper published in Nature Communications, authored by Dr. Laura-Oana Albulescu together with Professor Nicholas Casewell at the Liverpool School of Tropical Medicine’s (LSTM’s) Centre for Snakebite Research and Interventions and AIMMS researcher Dr. Jeroen Kool at the VU’s division of Bio-Analytical Chemistry, demonstrates a new way of treating snakebites. The team has shown that the repurposing of combinations of existing Phase II drug candidates provides an effective therapeutic approach for the treatment of bites from some of the deadliest haemotoxic snakes.

The paper entitled "A therapeutic combination of two small molecule toxin inhibitors provides pancontinental preclinical efficacy against viper snakebite" showed that a combination of two small molecule toxin inhibitors protected mice against the venoms from multiple species of vipers. The findings suggest that combinations of toxin inhibitors could lead to the development of broad-spectrum therapies to treat snakebites.

Snakebites result in approximately 138,000 deaths a year in the rural communities of sub-Saharan Africa, South and Southeast Asia, and Central and South America, and 3 to 4 times more victims suffer from permanent morbidities after a snakebite (such as amputations or blindness). Differences in the composition of snake venoms mean that antibody-based antivenoms tend to only be effective against bites from a specific snake species.

The team explored the potential of using combinations of small molecule toxin inhibitors as broad-spectrum therapeutics against snake venom. In laboratory experiments, the authors found that a number of molecules that had undergone phase-2 clinical trials were capable of neutralizing viper venoms by inhibiting different families of toxins. In experiments involving mice, a single dose of a combination of two inhibitors (marimastat and varespladib) was administered 15 minutes after viper venom, and the animals were monitored for 24 hours afterwards. The authors found that these molecules were capable of preventing the death of the mice, and were shown to be effective against the venoms from a range of medically important vipers from Africa, South Asia and Central America.

The authors conclude that their data provides evidence that combinations of small molecule toxin inhibitors can neutralize medically important snake venoms. Further preclinical studies are required, but the team suggests that these therapies could, in the future, provide safe, affordable and orally administrable prehospital treatments for snakebites.

Dr. Jeroen Kool has been interviewed both by the Dutch newspaper Trouw and by the Dutch broadcoast NPO Radio 1 (Spraakmakers, 16 December 2020, 10:30-11:30, (item starts at 0:03:55)).