Venomous snails pave path to new pain treatments

March 28th 2022

We have previously written about the value of studying various species beyond those animals that are commonly used in research—mice, rats, primates and fish. One of those species includes Predatory Marine Snails, a.k.a., cone snails. These snails are used in medical research because they have up to 250 venoms which they use to paralyze their prey. The compounds found in this venom have been used to treat chronic pain, diabetes and other human maladies. But the cone snails’ venom has more secrets yet to be revealed. In a new study published in Science Advances, researchers report that a group of cone snails produces a venom compound similar to the hormone somatostatin. 

Here, a snail extends its proboscis and discharges a shot of venom into a latex-topped tube. Credit: Alex Holt/NIST

Somatostatin is a hormone that, in humans and many other vertebrates, is generally an inhibitor—that is, it stops a neurochemical reaction in the body.. It is the main inhibitor of growth hormone, and can be used to treat the excessive growth disorder acromegaly. It also inhibits hormones in the pancreas and blocks signals of pain and inflammation.

Iris Bea Ramiro, the first author of this publication, was studying Conus rolani, a species of the Asprella cone snail.

“No one in our lab was working on it at that time,” she says. “I was just looking to identify any small peptide (chain of amino acids) from the venom of C. rolani that had unusual or interesting activity in mice.”

She found one. A small peptide from the venom caused mice to become sluggish or unresponsive. But it was slow-acting, unlike  other cone snail venoms that acted almost immediately. The peptide that Ramiro found had a few similarities to the hormone somatostatin but not enough to say conclusively that the venom peptide (now called Consomatin Ro1) and the human hormone were functionally related. 

Ramiro’s collaborator, Frank Whitby, used a technique called X-ray crystallography to determine the structure of Consomatin Ro1.

“This was an important contribution because it showed that Consomatin Ro1 does not resemble somatostatin but rather resembles a drug analog of somatostatin called octreotide,” says Christopher Hill.

It took a year, Ramiro says, to confirm that the peptide that she’d originally isolated from the C. rolani snail activates two of the five human receptors for somatostatin “with unique selectivity.” The study showed that Consomatin Ro1 can block pain in mice with efficiency similar to morphine, and it may be used to block pain so that prey doesn’t know that it has been struck.

Next, the research team wants to investigate the origin of Consomatin Ro1 in snails, as well as better understand the potential of the compound as an anti-inflammatory or pain reliever. They’ll also look to see if modifications to the compound could make it even more useful.

Like so many breakthroughs in science and medicine, the study of cone snail venom dates back to the 1970s (that’s more than 50 years!!). Decades of study have provided an abundance of information about how venom compounds interact with the bodies of prey fish, including how the venoms interact with receptors in the body and overwhelm natural biochemical processes. And, as this study demonstrates, there is still a lot more to learn.

~Speaking of Research
Content adapted from the press release.