Australian spider venom helps prevent stroke damage

March 22, 2017 § Leave a comment

The moderately venomous Australian funnel-web spider Hadronyche infensa Courtesy of Bastian Rast

The moderately venomous Australian funnel-web spider Hadronyche infensa
Courtesy of Bastian Rast

Researchers at Australia’s University of Queensland have identified a peptide from spider venom that can protect mice from brain damage if it’s given up to eight hours after an ischemic stroke. The researchers presented their work this week in the journal Proceedings of the National Academy of Sciences.

The only drug available to treat strokes is tissue plasminogen activator, or tPA, which works by breaking up the clots that cause ischemic strokes. At too high of a dose, however, tPA can induce hemorrhaging. Because of this risk, the drug is utilized for only about three percent of stroke cases worldwide.

Stroke is “the second-biggest cause of mortality in the world, and we don’t really have a drug to treat these patients,” says senior author Glenn F. King the University of Queensland’s Institute for Molecular Bioscience.

Ischemic strokes are more common than blood vessel-bursting hemorrhagic strokes and occur when an obstruction in the brain’s blood vessels prevents oxygen from reaching neurons. In the absence of oxygen, the neurons begin to break down glucose by anaerobic respiration. This creates lactic acid as a byproduct. The lactic acid causes a drop in local pH that leads to toxic acidosis and cell death.

King and colleagues had previously shown that the peptide PcTx1 found in the venom of the South American tarantula Psalmopoeus cambridgei was effective in preventing cell death in mice if given up to two hours after a stroke. According to King, a Ph.D. student in his lab who was performing genetic sequencing on the venom gland of the Hadronyche infensa spider happened to identify a molecule, Hi1a. Hi1a was strikingly similar to PcTx1. H. infensa is native to Australia and a relative of the deadly Sydney funnel-web spider, but its venom is much less lethal.

Hi1a has a structure similar to two PcTx1 molecules joined together but has a different mechanism of action that makes its binding much more difficult to reverse. When Hi1a binds to an ASIC1a channel, it prevents the channel from activating, which averts the neurotoxic death cascade from occurring.

To examine Hi1a’s ability to protect neurons from stroke damage, the researchers first synthesized the peptide in bacterial cultures. They then injected it into mice at two, four or eight hours after an ischemic stroke had been induced.

“What surprised me the most was how well it worked at eight hours,” says King. Even at four hours, he says, they were able to protect the area directly surrounding the clot that’s been believed to die “very quickly and very irreversibly. That’s never really been seen before.”

Jorge Ghiso at New York University’s Langone Medical Center, who was not involved in the study, notes the peptide’s long-acting ability to protect neurons. “It’s very promising in the sense that the molecule provides a wider therapeutic window than tissue plasminogen activator to efficiently reverse the damage produced by the ischemic stroke”, he says. The peptide “has been already tested up to eight hours after stroke onset, and it works in a very low dose, which are both encouraging findings for future preclinical studies.”

King plans to examine the peptide’s activity over longer period of times, and hopes once the peptide’s ability to treat hemorrhagic strokes has next been examined, it could move into clinical trials within the next 18 months to two years. He envisions it eventually be implemented into a medication that would be a boon to rural patients who live far from medical centers.

“They’re going to get moved into a city hospital, and during that time, the brain is just dying,” he says. A drug that could treat both ischemic and hemorrhagic strokes “gives the first responders the opportunity to give the drug without any triage, and that’s going to really save a lot of neurons.”

This post was written by John Arnst, ASBMB Today’s science writer

Leave a Reply

Your email address will not be published. Required fields are marked *

What’s this?

You are currently reading Australian spider venom helps prevent stroke damage at Wild Types.