An international team of researchers — led by University of Utah scientists — has identified a new hope in treating diabetes and hormone disorders: Toxins found in one of the most venomous animals on Earth.
For a study published earlier this week in the journal Nature Communications, researchers examined the venom of a predatory marine cone snail. To hunt their prey, cone snails will “hijack” their prey’s blood sugar regulation using a lethal substance called consomatin.
As it turns out, the scientists noticed that this venom mimics a human hormone called somatostatin, which regulates blood sugar and hormone levels in the body.
Helene Safavi, the senior author of the study, and an associate professor of biochemistry at the University of Utah, explained that, while sourcing venomous sources might sound counterintuitive, these toxins are extremely precise and can be very useful in treating disease.
“Venomous animals have, through evolution, fine-tuned venom components to hit a particular target in the prey and disrupt it,” Safavi said in a statement.
“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, she said, “it’s a bit of a shortcut.”
This is because consomatin has specific, long-lasting effects, and appears to be more stable and specific than the human hormone. This makes it a promising “blueprint for drug design.”
Somatostatin acts like a “brake pedal” for a number of processes in the human body, like preventing levels of blood sugar or hormones from rising too high, the university explained.
By isolating the consomatin in a petri dish, the researchers found that it interacts with one of the same proteins that somatostatin does, delivering similar results.
However, somatostatin interacts with several proteins, and consomatin only interacts with one, which means that they could fine-tune hormone and blood sugar levels without tampering with the levels of other molecules.
The researchers even said that the cone snail’s toxins could more precisely target hormone levels compared to most synthetic drugs — drugs that are an important element of care for people with diabetes, or whose bodies overproduce growth hormones.
The cone snail is also theorized to use the consomatin alongside another insulin-like material, just like humans.
“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,” said Ho Yan Yeung, a postdoctoral researcher in biochemistry and the first author of the study.
“It means that there might not only be insulin and somatostatin-like toxins in the venom,” Yeung said. “There could potentially be other toxins that have glucose-regulating properties too.”
But… how do these highly selective toxins get harvested, and ultimately, help people in need?
The chemistry of cone snails
Researchers traveled to the Philippines, where cone snails reside, to collect samples for their study.
The venom of these snails is not just deadly to their natural prey — like worms, mollusks, and fish — but also to humans.
“Conus geographus can be aggressive and has been reported to have killed people – about 40 human fatalities have been reported,” Safavi told Cosmos, noting that the collection of snails was “potentially dangerous.”
With the expert experience of the research team (the university’s School of Biological Sciences has been a hotspot for cone snail venom research since 1970), they used long tongs to move the snails into large plastic containers.
“When we get back to the boat we transfer the snails to a bucket and take them back to the lab where we continue to handle them with great care,” Safavi told Cosmos.
From there, the team extracted venom from the snails to conduct their testing.
Although the consomatin yielded exciting results, it could still be too dangerous to use as a therapeutic. That said, by studying its structure, researchers can begin to design drugs for endocrine disorders with these key elements in mind.
“The next steps for us are to use this and other cone snail consomatins to make drug analogs that can be used to detect and treat different types of neuroendocrine cancers,” Safavi told Cosmos, “and also make analogs that can be used as new pain therapeutics.”
Although the scientists have this newfound knowledge on their side, they remain humbled by the evolutionary power of their lethal invertebrate colleagues.
“We’ve been trying to do medicinal chemistry and drug development for a few hundred years, sometimes badly,” Savafi said. “Cone snails have had a lot of time to do it really well.”
Yeung chimed in: “Cone snails are just really good chemists.”
Header image courtesy of University of Utah
