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Deadly Sea Snail Toxin Holds Promise For Diabetes Drugs: Study‌

by Zenger
August 21, 2024 at 3:00 pm
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<p>Dr. Ho Yan Yeung, PhD, first author of the study (left) and Dr. Thomas Koch also an author of the study (right) examined a freshly collected batch of cone snails. SAFAVI LAB VIA SWNS</p>
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Deadly sea snail poison could be key to making better drugs to treat diabetes, according to a new study. The toxin from one of the most venomous creatures on the planet may lead to new medicines for the condition and hormone disorders, say scientists.

They have identified a component within the venom of a deadly marine snail, called the geography cone, that mimics a human hormone called somatostatin, which regulates the levels of blood sugar and several hormones in the human body.

The researchers say the hormone-like toxin’s specific, long-lasting effects, which help the snail hunt its prey, could also help scientists design better drugs for people with diabetes and potentially deadly hormone disorders.

The team, led by scientists from the University of Utah in the United States, believe the somatostatin-like toxin could hold the key to improving medications.

They explained that somatostatin acts like a brake pedal for many processes in the human body, preventing the levels of blood sugar, several hormones, and many other important molecules from rising dangerously high.

The researchers found that the cone snail toxin, called consomatin, works similarly. However, consomatin is more stable and specific than the human hormone, which makes it a “promising” blueprint for drug design, according to the results published in the journal Nature Communications.

By measuring how consomatin interacts with somatostatin’s targets in human cells in a dish, the research team discovered that consomatin interacts with one of the same proteins that somatostatin does.

However, while somatostatin directly interacts with several proteins, consomatin only interacts with one. The researchers explained that the fine-tuned targeting means that the cone snail toxin affects hormone levels and blood sugar levels, but not the levels of several other molecules.

Dr. Ho Yan Yeung, PhD, first author of the study (left) and Dr. Thomas Koch also an author of the study (right) examined a freshly collected batch of cone snails. SAFAVI LAB VIA SWNS

They said the cone snail toxin is more precisely targeted than the most specific synthetic drugs designed to regulate hormone levels, such as drugs that regulate growth hormone.

Consomatin’s effects on blood sugar could make it dangerous to use as a therapeutic, but by studying its structure, researchers could start to design drugs for endocrine disorders that have fewer side effects.

Consomatin also lasts far longer in the body than the human hormone, due to the inclusion of an unusual amino acid that makes it difficult to break down.

The researchers said that is a “useful” feature for pharmaceutical researchers looking for ways to make drugs that will have long-lasting benefits.

Senior author Professor Helena Safavi, of the University of Utah, explained that the toxins’ lethality is often aided by pinpoint targeting of specific molecules in the victim’s body.

She says that the same precision can be “extraordinarily useful” when treating disease. Safavi said: “Venomous animals have, through evolution, fine-tuned venom components to hit a particular target in the prey and disrupt it.

“If you take one individual component out of the venom mixture and look at how it disrupts normal physiology, that pathway is often really relevant in disease.” She described it as “a bit of a shortcut” for medicinal chemists.

Safavi explained that consomatin shares an evolutionary lineage with somatostatin, but over millions of years of evolution, the cone snail turned its own hormone into a weapon.

A freshly collected batch of venomous cone snails. SAFAVI LAB VIA SWNS

She said: “For the cone snail’s fishy prey, consomatin’s deadly effects hinge on its ability to prevent blood sugar levels from rising.

“And importantly, consomatin doesn’t work alone.” Safavi’s team had previously found that cone snail venom includes another toxin that resembles insulin, lowering the level of blood sugar so quickly that the cone snail’s prey becomes nonresponsive.

Then, consomatin keeps blood sugar levels from recovering.

Study first author Dr. Ho Yan Yeung, also of the University of Utah, said: “We think the cone snail developed this highly selective toxin to work together with the insulin-like toxin to bring down blood glucose to a really low level.”

She explained that the fact that several parts of the cone snail’s venom target blood sugar regulation hints that it could include many other molecules that do similar things.

Dr. Yeung said: “It means that there might not only be insulin and somatostatin-like toxins in the venom. There could potentially be other toxins that have glucose-regulating properties too.”

It may seem surprising that a snail is able to outperform the best human chemists at drug design, but Safavi says that the cone snails have evolutionary time on their side.

She said: “We’ve been trying to do medicinal chemistry and drug development for a few hundred years, sometimes badly.

“Cone snails have had a lot of time to do it really well.”

Dr. Yeung added: “Cone snails are just really good chemists.”

 

     

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