Study of tarantula toxin opens door to next-gen drugs for chronic pain
Tarantula venom is not something people would normally associate with relief from pain, but strangely enough, the ingredients within it could hold the key to new medicines that offer just that, and without some of the common side effects. A new understanding of the way tarantula toxins shut down electrical signals in the spider’s prey has given scientists hope of recreating this effect, but in a positive way through advanced drugs that treat chronic pain.
This year we've looked at a couple of examples of how tarantula venom could inspire new pain-relief drugs that treat irritable bowel syndrome or avoid the side effects and risk of addiction associated with opioid-based medications. Similarly, the latest breakthrough from the University of Washington could lead to alternatives to opioid-based drugs, by focusing on the way the venom interferes with electrical signaling in nerve cells.
More specifically, the scientists used high-resolution cryo-electron microscopy to examine how the tarantula’s poison acts on small sensors on sodium channels in the cell membranes that generate electrical currents. Called voltage sensors, these normally send signals that operate nerves and muscles, but the venom serves to lock these down so that they remain inactive.
“The action of the toxin has to be immediate because the tarantula has to immobilize its prey before it takes off,” says William Catterall, senior author of the study.
This new perspective on how this mechanism functions enabled the team to create a model featuring a toxin-binding region taken from a type of human sodium channel called Nav1.7. This allowed them to study the molecular configuration of the tarantula toxin as it binds to the receptor site, which in turn illuminated the structural basis of the locked-down voltage sensor.
What makes this advance so significant is that Nav.17 plays an essential role in transmitting pain information from the peripheral nervous system to the spinal cord and brain. In this way, the discovery opens the door to the pursuit of advanced drugs that recreate the lockdown effects of the tarantula venom, and potentially relieve chronic pain without the need for opioids.
“Our structure of this potent tarantula toxin trapping the voltage sensor of Nav1.7 in the resting state provides a molecular template for future structure-based drug design of next-generation pain therapeutics that would block function of Nav1.7 sodium channels,” says Catterall.
The research was published in the journal Molecular Cell.
Source: University of Washington