Research: Pain researchers uncover secrets for box jelly venom –



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Researchers at the University of Sydney have discovered an antidote to the deadly bite given by Earth's most poisonous creature – the Australian jellyfish.

The Australian Box Jellyfish (Chironex fleckeri) has about 60 tentacles that can grow up to three feet in length. Each tentacle has millions of microscopic hooks full of poison.

Each box of jellyfish carries enough venom to kill more than 60 humans.

A single sting in a human will cause skin necrosis, excruciating pain and, if the venom dose is large enough, cardiac arrest and death within minutes.

Associate Professor Greg Neely and Dr. Raymond (Man-Tat) Lau and their team of pain researchers at the Charles Perkins Center at the University of Sydney were studying how the water-box poison works when they made the discovery .

They have discovered a remedy that blocks the symptoms of a jellyfish sting if administered to the skin within 15 minutes after contact.

The antidote was shown to work on human cells outside the body and then tested effectively on live mice.

Researchers now hope to develop a topical application for humans.

"We were seeing how the venom works, to try to understand better how that causes pain. Using new CRISPR genome-editing techniques, we were able to quickly identify how this poison kills human cells. Fortunately, there was already a drug that could act in the way the venom uses to kill cells, and when we tried this drug as a poison antidote in mice, we found that it could block tissue healing and pain related to jellyfish bites " , said Associate Professor Neely. "It's super exciting."

Published in the newspaper Communications of nature today, the study used the complete genome edition of CRISPR to identify how the venom works. Genome editing is a technology that allows scientists to add, remove, or change genetic material in an organism's DNA.

In the study, the researchers took a barrel of millions of human cells and eliminated a different human gene in each. Then they added the jellyfish venom box – which kills the cells in high doses – and searched for cells that survived. From all genome screening, researchers have identified human factors that are necessary for the venom to work.

"The jelly venom pathway we identified in this study requires cholesterol, and since there are many cholesterol-lowering drugs available, we could try to block that pathway to see how that affected the activity of the venom. We took one of these drugs, which we know to be safe for human use, and we used it against the poison, and it worked, "said Dr. Lau, who is the lead author of the article. "It's a molecular antidote."

"It's the first molecular dissection of how this kind of venom works, and how possible any venom works," said Dr. Lau. "I have not seen a study like this for any other poison."

"We know the drug will completely stop necrosis, skin healing and pain when applied to the skin," said associate professor Neely, who is the senior author of the article. "We still do not know if this will prevent a heart attack. That will require further research and we are applying for funding to continue this work."

Found in coastal waters in northern Australia and in waters around the Philippines, the jellyfish from the box is extremely dangerous. They not only float, they can actively swim, gaining speed of 7.5 miles per hour when they are hunting. They feed on shallow water, especially small fish and shrimp.

There are two types of jellyfish, the Irukandji, which is tiny, and the Chironex fleckeriwhich is about three meters long. "We studied the bigger, more poisonous and scary," said Associate Professor Neely. "Our drugs work on the big beast. We still do not know if it works in other jellyfish, but we know it works in the most deadly. "

The venom used in the study was collected from a box of jellyfish in the waters of Cairns by Associate Professor Jamie Seymour at James Cook University.

Evidence suggests that the only current treatment for a sting is to dry the area with vinegar for 30 seconds or run very hot water over the affected area for 20 minutes. If it is an important prick, continuous CPR is needed to keep the heart from pounding.

"Our antidote is a drug that blocks the poison," said associate professor Neely. "You need to put it on the site in 15 minutes. In our study, we inject it. But the plan would be a spray or a topical cream. The argument against a cream is when you are stung leaves many stings on you, so if you rub the cream on it may be squeezing more venom into you. But if you spray it, it can neutralize what's left of your body. "

Associate Professor Neely and his team are now looking for potential partners to work on making the drug available to the public.

The work of Associate Professor Neely's team on functional genomics and chronic pain study at the Charles Perkins Center and he leads the Sydney Genome Edition Initiative at the University of Sydney. They are studying a number of Australian mortal creatures – the water box, and a wide variety of other venomous animals – to understand what causes the pain.

By 2018, pain and chronic pain cost $ 139 billion for the Australian economy and are moving to $ 215 billion by 2050, according to Pain Australia.

"Most of our work is directed to the development of non-addictive analgesics for humans," said associate professor Neely. "One way to do this is to find out how the painful poisons of Australian creatures work using the new CRISPR technology. It's super cool.

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