In an international collaboration, researchers led by Matthew Levin of the California Academy of Sciences and Stephen Samuel of Trinity College Dublin have demonstrated that they may be edging towards the development of a universal snake venom antidote that could potentially dramatically improve the survival rates of victims of venomous snakebites. The study has been published in The Journal of Tropical Medicine.
Venomous snakebites are responsible for a considerable number of deaths each year. Of the 5 million snakebites reported each year, it is estimated that 2 million result in the injection of venom and between 94,000 and 125,000 will result in death. Furthermore, approximately 75% of these fatalities occur before reaching the hospital, which is mainly due to difficulties in treating these bites outside of a hospital setting as they require intravenous injections of antidotes. Therefore, developing treatments that are easier to administer in the field has the potential to save many lives, which is what this team has been working on.
During this current study, the researchers investigated the efficacy of an antiparalytic agent administered intranasally (IN) in mice challenged with a deadly dose of snake venom. The treatment, neostigmine, is an acetylcholinesterase inhibitor that is recommended by the WHO for the treatment of neurotoxic snakebites. It is thought to function by increasing the availability of the neurotransmitter acetylcholine at the junctions between the nervous system and the muscular system, thus reducing the neuromuscular block induced by the venom.
Mice were divided into groups that received varying lethal doses of venom, followed by IN neostigmine at different time intervals: either between 1-2 minutes after venom challenge or 10 minutes after. 100% of the control mice died in the study, but 10/15 of the mice receiving the lower (but still fatal) dose of the venom and treatment within 10 minutes survived and recovered. Although all of the mice receiving the higher dose of venom (2-5 times higher than the lethal dose) died, those receiving just a single dose of neostigmine survived for a significantly longer period than the control mice.
The study raises the possibility that this agent could be combined with specific antivenoms in order to form a more effective antidote. “Antivenom is necessary, but not sufficient to manage the problem. Its limitations are fairly well known at this point and we need a better bridge to survival. It’s ironic that virtually every medical organization and practitioner wears the snake symbol, yet we have no real effective treatments for the people getting bitten,” says lead author Dr. Lewin in a news-release. “Ninety-eight percent of snakebite victims live in poverty, which is perhaps why funding and innovation are lacking. The bottom line is that no one should die from a snake bite in the twenty-first century, and we’re optimistic about this promising step.”
The potentials of this treatment have been demonstrated in previous studies. In April last year, a volunteer was paralyzed in order to mimic neurotoxic snake venom. The paralysis resulted in respiratory distress, similar to what would be expected from certain venomous snakebites. The volunteer recovered a mere 20 minutes after IN neostigmine administration. A later study conducted in June involved a snakebite victim in India who failed to fully recover from 30 vials of antivenom. The patient remained weak and was paralyzed in her facial muscles, but IN neostigmine managed to reverse this facial paralysis in just 30 minutes. Two weeks later she was fully recovered.
The team is now collaborating with a snake venom expert, Sakthivel Vaiyapuri of Reading University, in order to test this therapy in combination with various antivenoms.