about 1.8 million Every year, 138,000 people are bitten by snakes around the world, of which 138,000 die and a further 400,000 are left with permanent injuries or disabilities.
Many cobras Poison that damages tissue These toxins cannot be treated with current antitoxins. We have discovered that cheap, readily available anticoagulants can be repurposed as antidotes for these toxins.
use CRISPR Gene editing techniques have allowed us to learn more about how these toxins attack cells. And Heparinoids It can protect the tissue from toxins. the study Published today Science Translational Medicine.
Snakebites are a serious problem
Snake venom They consist of a variety of compounds that typically target the heart, nervous system, or tissues at the site of exposure (such as skin or muscle).
Much of the research on snakebites has understandably focused on the most deadly venoms, with the result that venoms that are less deadly but do cause long-term problems – such as cobra venom – have received less attention.
In areas where cobras live, a severe snake bite can have devastating effects such as amputations, leading to life-changing injuries and loss of livelihood. who It hopes to declare snakebite a “category A” neglected tropical disease and reduce the burden of snakebite. Half by 2030.
Currently, the only treatment for snakebite is AntitoxinIt is made by administering a small amount of poison to a non-human animal and then harvesting the venom. antibody They produce accordingly.
Although antivenoms are life-saving, they do have some drawbacks: each antivenom is specific to one or more snake species, is very expensive (if it can be obtained at all), needs to be kept refrigerated, and must be administered by injection in a hospital.
Furthermore, the antitoxin does not prevent localized tissue damage, primarily because the antibodies that make up the antitoxin are too large to reach peripheral tissues such as the hands and feet.
How cobra venom kills cells
Our team (from the University of Sydney in Australia, the Liverpool School of Tropical Medicine in the UK, and the Clodomiro Picado Institute in Costa Rica) began looking at other options for treating snakebites.
First, we wanted to understand how these venoms work. We started with cobras, which live in Africa and South Asia.
We took venom from the African spitting cobra, which is known to cause tissue damage, and did what’s called a whole genome test. CRISPR screen.
We took large numbers of human cells and used CRISPR gene editing technology to disable different genes across the human genome in each cell. CRISPR technology uses special enzymes to delete or change specific parts of the DNA in cells.
They then exposed all the cells to cobra venom to see which cells survived and which died.
Because the surviving cells must have lacked whatever the poison needed to injure humans, we were able to quickly identify what these characteristics were.
They discovered that the venom of various cobras requires certain enzymes to kill human cells. These enzymes are: Heparan and heparin sulfate.
Heparan sulfate is present on the surface of human and animal cells and is released from cells when the immune system responds to a threat.
The importance of these molecules makes intuitive sense: snake venoms have co-evolved with their targets, but heparan and heparin have remained largely unchanged throughout evolution, allowing the venom to hijack a common part of the animal’s physiology to cause damage.
How heparin decoy reduces tissue damage
Heparin has been used as an anticoagulant for almost 100 years.
We tested this drug in human cells to see if injecting large amounts of free heparin into the body could be used as a decoy for the toxin. Surprisingly, this worked – even when heparin was added to the cells after the toxin had been administered, the toxin no longer caused cell death.
We also tested heparin against the venom of the distantly related Asian cobra and found a similar protective effect. Chinzaparin It may be possible to reduce tissue damage in mice artificially “snakebite”ed.
To understand how heparin blocks the toxin, we isolated the toxin into its major components.Cytotoxic three-finger toxins“These are the main causes of tissue damage. Until now, there were no known drugs that could treat these toxins.
The next step is to test the effects of heparin in humans.
Cheaper, more accessible snakebite treatment
Our goal is to create a heparin bite treatment device that contains a heparin-like drug called a heparinoid, which would be similar to the EpiPen adrenaline syringes often carried by people at risk of having a severe allergic reaction. These devices could be distributed to people at high risk of cobra bites.
Heparinoids are already inexpensive, essential drugs used to prevent blood clots, and the U.S. Food and Drug Administration has approved them for human self-administration, potentially shortening the time needed to bring drugs to market.
Heparinoids are stable at room temperature, making the drugs more accessible in remote areas and allowing for faster delivery to the field.
Other studies The usefulness of Drug Repurposing For snakebite treatment. These drug combinations may herald a new era of snake envenoming that doesn’t rely solely on expensive antivenom.
In our lab, we use CRISPR screening to Box jellyfish venom And now we’re looking at other common venoms, from blue flies to black snakes, and our screening techniques can reveal a wealth of information about venom.
Though it’s still early days, we’re finding that many toxins rely on overlapping targets to attach to cells. All this research leads to the loftier goal of creating universal, broad-spectrum antidotes for toxins.
Thien DuToxicogenomics PhD Candidate, University of Sydney and Greg NeelyProfessor of Functional Genomics, University of Sydney
This article is reprinted from conversation Published under a Creative Commons license. Original Article.
