A generic therapy for venomous snakebites
One of the most common lethal symptoms of snakebites is neurotoxicity, which causes damage to the nervous system by neurotoxins blocking the nerve transmission. To inhibit the activity of these neurotoxins, the scientists will use molecules that mimic the receptors to which those toxins bind in the body.
An earlier pilot by Kool and colleagues showed that such 'decoy receptors' offer great potential to neutralize venom neurotoxins, irrespective of snake species (unlike antivenom) and at lower doses than antivenom. This research could therefore lead to a single, generic therapy for the treatment of neurotoxic snakebites worldwide.
First aid after a snakebite
In many developing countries it takes a while before you can be treated in a hospital after a snakebite due to the long travel, often by foot, to the nearest hospital or the absence of the right antivenom. Small molecule toxin inhibitors offer great potential to deliver inexpensive, safe and efficacious oral interventions (such as a pill) on the spot soon after a snakebite, prior to subsequent admission to a hospital.
Only a handful of toxin inhibitors have been robustly explored to date. Kool and his colleagues are therefore going to screen more than 50,000 molecules using high throughput screening techniques to find molecules that neutralize pathological toxins in venoms of many different snake species. Among those molecules, also all registered small molecule drugs developed to date for treatment of other diseases will be screened for their potential to become repurposing candidates to treat snakebites. The concept aims at developing new orally available generic snakebite drugs. At the end of the project the scientists will deliver a portfolio of molecules ready for translation into clinical studies to assess their tolerability and efficacy as snakebite therapeutics.
Wellcome is a politically and financially independent global charitable foundation, funded by an investment portfolio. Kool, Casewell and Ulens received two Snakebite Grants. These grants are meant for scientists working on innovative approaches to discover and develop next generation treatments for snakebite.
Image credits: Jory van Thiel