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Photos: Deadly cone snail venom could yield miracle drug for diabetes

Consomatin, a toxin from the marine cone snail, demonstrates greater stability and specificity compared to human somatostatin.

Published: Aug 20, 2024 04:13 AM EST

Sujita Sinha

8 days ago

Venomous marine cone snail.

Safavi Lab

A groundbreaking study reveals that one of the most venomous animals on the planet, the marine cone snail, may hold the key to treating diabetes and hormone disorders.

Researchers from the University of Utah, working with an international team, have uncovered a crucial component within the cone snail’s venom that mimics a human hormone called somatostatin.

This discovery could pave the way for developing more effective treatments for these serious conditions.

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Unveiling the mystery of cone snail venom
The venom of the deadly geography cone snail has long intrigued scientists due to its potency and specificity. The research highlights how the snail's venom contains a toxin, consomatin, that closely resembles somatostatin, a hormone that plays a vital role in regulating blood sugar and various hormones. This novel discovery opens doors to potential advancements in drug design for managing diabetes and hormone disorders.
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A promising blueprint for drug development
Somatostatin functions as a regulatory brake within the human body, preventing excessive rises in blood sugar and hormone levels. Researchers found that consomatin, the somatostatin-like toxin from the cone snail, operates with a similar mechanism. However, consomatin is distinguished by its greater stability and specificity compared to human somatostatin. This increased stability is due to an unusual amino acid that makes consomatin more resistant to breakdown. The team observed that consomatin interacts with one of the same proteins as somatostatin but does so with higher precision. Unlike somatostatin, which affects several proteins, consomatin targets only one, making it a potentially more focused tool for drug development. The specificity of consomatin is remarkable, even surpassing that of the most advanced synthetic drugs designed to regulate hormone levels.
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Enhancing drug stability and efficacy
One of the critical advantages of consomatin is its prolonged duration in the body. Human somatostatin has a brief half-life of 1-3 minutes, rapidly breaking down after production. In contrast, consomatin’s structure, akin to the somatostatin-based drug analog Octreotide, prevents rapid degradation. This feature is essential for developing drugs with sustained effects, offering potential benefits for long-term treatments.
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Learning from venomous evolution
The use of venom for drug development might seem unconventional, but Helena Safavi, associate professor of biochemistry at the Spencer Fox Eccles School of Medicine (SFESOM), explains the evolutionary advantage of such venoms. "Venomous animals have, through evolution, fine-tuned venom components to hit a particular target in the prey and disrupt it,” Safavi says in the press release. “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.” For medicinal chemists, this represents a significant shortcut. Consomatin’s evolutionary lineage is a testament to nature’s ingenuity. The cone snail evolved its toxin to function similarly to somatostatin, but with a lethal twist. For the snail's aquatic prey, consomatin prevents blood sugar levels from rising, complementing another toxin in the venom that mimics insulin and lowers blood sugar quickly.
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The dual action of cone snail venom
According to Ho Yan Yeung, a postdoctoral researcher at SFESOM and the study's lead author, consomatin and its insulin-like counterpart work together to regulate blood glucose levels effectively. "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,” Yeung explains. “Consomatin keeps blood sugar levels from recovering.” This dual action indicates that the venom may contain additional components with similar glucose-regulating properties, potentially leading to new therapeutic discoveries.
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Consomatin's potential applications
Despite its promise, consomatin may not be suitable for direct diabetes treatment due to its powerful glucose-lowering effect. However, Yeung sees potential in using consomatin for treating growth hormone disorders such as acromegaly and as a diagnostic tool for neuroendocrine cancers. In an interaction with Interesting Engineering (IE), Yeung notes, "The somatostatin-like toxin (G1) described in our study may not be a useful candidate for the treatment of diabetes, but it could be used for growth hormone disorders and neuroendocrine cancers." Yeung also highlights ongoing research on other cone snail toxins with promising results as pain therapeutics, further demonstrating the potential of venom-derived drugs.
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Evolutionary precision in drug development
The evolutionary process of the cone snail has resulted in a toxin with remarkable precision and effectiveness, often surpassing synthetic drugs. "The existing somatostatin-based drug analog, Octreotide, was developed in the 80s," Yeung says. "However, the cone snail evolves a toxin structure that shows striking similarities with the drug Octreotide but with an even more targeted effect." This insight underscores the efficiency of nature’s design compared to traditional drug development methods, which can be time-consuming and costly. "Had we discovered this somatostatin-like toxin earlier, we would have been able to bypass all the time-consuming and costly drug development processes," Yeung told IE.
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Broader implications for glucose regulation research
The discovery of multiple blood sugar-regulating toxins in cone snail venom suggests a broader understanding of glucose regulation might be possible. "We believe that the cone snail is a very smart physiologist that deeply understands how blood glucose regulation works and uses the knowledge to its advantage," Yeung asserts. "The toxin described in our study is another example of how nature has already perfected drug candidates for us." Yeung compares the consomatin discovery to other nature-based drugs, such as the GLP-1 based therapy from the Gila monster and the cone snail-derived FDA-approved drug, ziconotide. These examples illustrate the potential for natural compounds to inspire innovative drug development.
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Nature's superior chemists
It may seem astonishing that a snail's venom could outperform human chemists, but Safavi emphasizes the advantages of evolutionary time. "We’ve been trying to do medicinal chemistry and drug development for a few hundred years, sometimes badly,” she says. “Cone snails have had a lot of time to do it really well.” Yeung agrees, highlighting the cone snail’s expertise: “Cone snails are just really good chemists.” The study was published recently in the journal Nature Communications.