Scientists one step closer to universal ‘holy grail’ antivenom
Scientists have developed a treatment that prevents paralysis or death triggered by the antivenom of some of the world’s most terrifying snakes, including the black mamba and king cobra.
The breakthrough has been hailed as a “first step” towards creating a universal antivenom – long considered the ‘Holy Grail’ of snakebite research.
Each year, between 81,000 and 138,000 people die from snake bites across the globe. A further 400,000 suffer life-altering injuries, including amputations, sight loss and terrible open ulcers that never heal.
But treatment options have barely changed for a century. Not only is the development process laborious – it involves milking snakes and injecting horses with toxins – but side effects can be severe and therapies are snake-specific.
However, in a new study published last week, scientists unveiled a single human antibody that protects against venom from numerous dangerous snakes – including the monocled cobra (also known as the Indian spitting cobra), the king cobra (the longest venomous snake species worldwide) and the black mamba (which is notoriously feared in Africa).
“This study is a really exciting outcome because it really moves the boundaries of what we thought a single antibody would be capable of in the context of snakebite,” said Professor Nicholas Casewell, head of the Centre for Snakebite Research and Interventions at the Liverpool School of Tropical Medicine and co-author of the report.
In the study, published in Science Translational Medicine journal, researchers analysed proteins found in elapids – a family of around 300 mostly venomous snakes – to identify common toxins which cannot mutate or change.
They honed in on a type of three-finger toxin which is present across all elapid snakes and causes paralysis in bite victims. The team, which included researchers from the UK, US and India, then tested more than 50 billion different human antibodies to find any that blocked the venom.
One, called 95Mat5, stood out. In animal trials, all mice that received an injection of this antibody were protected from paralysis and death caused by venom from various elapid snakes.
“This antibody works against one of the major toxins found across numerous snake species that contribute to tens of thousands of deaths every year,” said Prof Joseph Jardine, an assistant professor of immunology and microbiology at Scripps Research in the US, and co-author of the report.
“This could be incredibly valuable for people in low- and middle-income countries that have the largest burden of deaths and injuries from snakebites.”
The team hopes 95Mat5 could form the basis of the first monoclonal antibody treatment used against snake bites. Because it would be based on a human molecule, rather than “foreign” horse antibodies, it should also be “safer than current antivenom”, said Prof Casewell.
“Scalability is unlikely to be a major challenge once an appropriate manufacturing partnership is in place,” he added, though he noted that reaching the rural regions most at risk is likely to remain a “major hurdle”.
Still, while the identification of 95Mat5 and the success in mice is a major moment, it will take some time for a drug to be available.
“There remain considerable challenges,” said Prof Casewell. “There are currently no monoclonal antibodies in clinical use for snakebite, so this would be several years away from implementation. We would need to assess safety and efficacy of the antibody in clinical trials first, before any approval for use in patients.
“Also, this antibody is only tackling one class of toxins – though this is an important class – so additional work needs to be done on discovering other antibodies or drugs that neutralise other types of toxins too.
“But if we can develop similar broadly inhibiting solutions for other toxin families … then in the long term we might be able to develop a combination therapy that does provide that global breadth,” Prof Casewell said.
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