Venom from the dangerous Australian funnel-web spider contains a protein that shuts down an ion channel known to become defective in brain cells following strokes, research from The University of Queensland and Monash University has found.
The small protein demonstrates great promise as a future stroke treatment, said UQ Institute for Molecular Bioscience researcher Professor Glenn King, who led the research.
“We believe that we have, for the first time, found a way to minimise the effects of brain damage after a stroke,” Professor King said. The small protein we discovered, Hi1a, blocks acid-sensing ion channels in the brain, which are key drivers of brain damage after stroke.
During preclinical studies, we found that a single dose of Hi1a administered up to eight hours after stroke protected brain tissue and drastically improved neurological performance. This world-first discovery will help us provide better outcomes for stroke survivors by limiting the brain damage and disability caused by this devastating injury."
Stroke Brain Damage
[caption id=“attachment_89096” align=“alignright” width=“330”] Australian Funnel Web Spider, male. Credit: Toby Hudson CC BY-SA 3.0[/caption]
Nearly 800,000 (approximately 795,000) people in the United States have a stroke every year, with about three in four being first-time strokes, according to the American Stroke Association. Stroke is a leading cause of long-term disability and the leading preventable cause of disability.
87% of strokes happen as a result of a clot or a mass blocking a blood vessel, cutting off blood flow to a part of the brain.
A clot-dissolving, or clot-busting, medication called tissue plasminogen activator (tPA) can be administered to prevent brain damage in such cases, but it needs to be given with 4 hours or it is ineffective in stopping cell death. Researchers are working to identify a better treatment and have discovered that a population of ion-channels called called acid-sensitive ion channels are critical drivers of brain damage after stroke.
The scientists were sequencing the DNA of the venom, which can kill a human in 15 minutes, and came across a small peptide, Hi1a, that looked promising. When they tested the compound on rats, they found that administrating Hi1a two hours after a stroke lowered the magnitude of brain damage in by 80 per cent.
Core Brain Protection
Professor King said he hopes this breakthrough could fundamentally improve outcomes for stroke patients.
“One of the most exciting things about Hi1a is that it provides exceptional levels of protection for eight hours after stroke onset, which is a remarkably long window of opportunity for treatment,” he said.
Hi1a even provides some protection to the core brain region most affected by oxygen deprivation, which is generally considered unrecoverable due to the rapid cell death caused by stroke. We are now working to secure financial support to fast-track this promising stroke therapy towards clinical trials."
Globally, approximately six million people die each year from strokes.
Irène R. Chassagnon et al Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a PNAS March 20, 2017 doi: 10.1073/pnas.1614728114
Image: Hellerhoff CC BY-SA 3.0. Defect of the blood-brain barrier after stroke shown in MRI.