In a scientific paper demonstrating multiple breakthroughs, scientists at Sydney and Liverpool have identified a commonly available blood thinner that doubles as an antidote to cobra venom.
The study relied on CRISPR gene modification technology to identify cells immune to snake venom and use them as case studies to figure out what would be the best mechanism for preventing necrosis from snake bites.
The authors describe snake bites in general as “the deadliest neglected tropical disease” and report that around 140,000 people every year die from them, with another 400,000 permanently wounded.
Snake venom comes in different forms. Cobra venom attacks cells directly causing necrosis, but also attacks the nervous system and can affect the heart and brain.
Antivenom is typically about 7 times as expensive as the average daily wage in countries where cobra bites are the highest, and many pharma companies will simply discontinue the products for this reason.
By examining the effect of cobra venom, what study author Professor Greg Heely refers to as a “three-finger toxin,” on human cells, he and his team found a cell pathway conserved in all known animal species that produces the related molecules heparan and heparin, the latter being a used as a blood thinner.
“Heparin is inexpensive, ubiquitous, and a World Health Organization-listed Essential Medicine. After successful human trials, it could be rolled out relatively quickly to become a cheap, safe, and effective drug for treating cobra bites,” says Ph.D. student and lead author, Tian Du, who like Professor Neely, resides at the University of Sydney, working in functional genomics.
Heparin and heparan are both targets of cobra venom, with heparan found on the cell surface and heparin being released during an immune response. Their similar structure means the venom can bind to both, and the “heparan/heparin sulfate biosynthesis pathway” was often the most heavily targeted component by the venom as a means to infiltrate cells, with 7 out of 11 components in the pathway attacked by the venom of the red spitting cobra, and 8 out of 11 by the venom of the black-necked spitting cobra.
The team used this knowledge to turn the heparin drug into an antidote that can stop necrosis in human cells and mice by flooding the bite zone with decoy molecules. The venom rapidly attacks the exogenous heparin, leaving the endogenous heparin and the cells containing it, intact.
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Cobras are part of the Elapidae family of snakes which include sea snakes, mambas, and coral snakes. In some parts of Asia and Africa, cobras are responsible for more bite deaths and amputations than any other group.
In an interesting secondary discovery, the team hypothesized how their method could be used to find other use cases for antivenoms. In a video explainer, Professor Neely says that there aren’t many different kinds of venom across the animal kingdom, and finding a way to crack the code of one offers the chance to develop antivenoms much more rapidly.
MORE BREAKTHROUGH MEDICINES: Scientists Find Potential Universal Anti-Venom to Treat Snakebites, from Kraits to King Cobras.
The three-finger toxins present in cobra venom are also found in the terribly toxic blue bottle jellyfish of Australia, which the team says is next on their list for antivenom research.
It was hypothesized when CRISPR first entered the public zeitgeist that it would be monopolized by wealthy industrialized nations to create a slew of aesthetic products and treatments to enhance beauty or longevity. It’s inspiring to see CRISPR be used directly for the benefit of the poorest and most vulnerable members of the world.
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