Ingredient in funnel web spider venom can protect cells from being destroyed by a stroke, even when given hours after the event, study shows 
 
 Doctors have stumbled on an unlikely source for a drug to ward off brain damage caused by strokes: the venom of one of the deadliest spiders in the world. 
 
 A bite from an Australian funnel web spider can kill a human in 15 minutes, but a harmless ingredient found in the venom of one species can protect brain cells from being destroyed by a stroke, even when given hours after the event, scientists say. 
 
 
 
 If the compound fares well in human trials, it could become the first drug that doctors have to protect against the devastating loss of neurons that strokes can cause. 
 
 Researchers discovered the protective molecule by chance as they sequenced the DNA of toxins in the venom of the Darling Downs funnel web spider (Hadronyche infensa) that lives in Queensland and New South Wales. 
 
 Venom from three spiders was gathered for the study after scientists trapped and “milked exhaustively” three spiders on Orchid beach, about 400km north of Brisbane. 
 
 The molecule, called Hi1a, stood out because it looked like two copies of another brain cell-protecting chemical stitched together. It was so intriguing that scientists decided to synthesise the compound and test its powers. “It proved to be even more potent,” said Glenn King at the University of Queensland’s centre for pain research. 
 
 Strokes occur when blood flow to the brain is interrupted and the brain is starved of oxygen. About 85% of strokes are caused by blockages in blood vessels in the brain, with the rest due to bleeds when vessels rupture. Approximately six million people a year die from stroke, making it the second largest cause of death worldwide after heart attacks. 
 
 
 
 When a stroke happens, the oxygen level in the brain drops. This forces the brain to burn its primary fuel, glucose, very differently. Instead of oxidising glucose for energy, the brain switches to a process called anaerobic glycolysis. The reaction releases energy to keep the brain working, but it also produces acid, which can cause brain cells to die. 
 
 
 
 In a series of studies on rats, King showed that a single small dose of the spider venom molecule protected neurons from induced strokes. The compound works by blocking what are called ion channels in cells, specifically those that respond to the onset of acidic conditions in the brain. 
 
 
 
 Reporting in the journal, Proceedings of the National Academy of Sciences, King describes how administering Hi1a two hours after stroke reduced the extent of brain damage in rats by 80%. But the compound was still effective eight hours after stroke, reducing the amount of brain damage by about 65% when compared with untreated animals. 
 
 
 
 Rats that had the compound recovered far better than those that went without. “The untreated rats performed very badly after stroke. Their neurological and motor performance were terrible,” said King. But treatment with Hi1a “almost restored these functions to normal,” he added. 
 
 
 
 The researchers hope to start human trials of the compound in the next two years, but have more experiments to perform first. These will test whether the molecule works in all cases of stroke and is safe to use when blood vessels rupture in the brain, rather than become blocked. In the latest study, the compound was infused directly into the brain, but the scientists have found since that nasal deliver works too. 
 
 
 
 If trials show that the compound works, it could potentially transform the treatment of stroke patients. There are no drugs on the market that can protect the brain from stroke injuries. The best hospitals can offer are infusions of clot-busting drugs if a clot is to blame, or a surgical procedure called endovascular thrombectomy, which physically pulls the clot from the brain. 
 
 
 
 Before doctors can administer clot-busting drugs, they must confirm with a brain scan that the stroke was caused by a blockage. This is because the treatment thins the blood and could make matters worse if the stroke was caused by a haemorrhage. If Hi1a is found to be safe for people who have had with brain bleeds, it could be given to patients as soon as they reach a doctor. “The drug could be given in the ambulance to most stroke patients before hospital arrival, maximising the number of neurons that can be saved,” said King. “This should diminish the mortality from stroke and provide much better outcomes for those that survive as more brain function will be retained.” 
 
 Kate Holmes at the Stroke Association, said it was unknown whether Hi1a could be an effective treatment in humans. “We welcome any treatment that has the potential to reduce the damage caused by stroke, particularly if this can benefit people who are unable to arrive at hospital quickly,” she added. “Current treatments must be given in half this time period and it is too early for us to know if this research can offer an alternative for stroke patients. 
 
 “We urge for stroke to be treated as an emergency. The sooner a person can get to hospital after a stroke, the sooner the right treatment can be received which can improve survival and help recovery,” she said. 
 
 
 
 • This article was amended on 22 March 2017 to clarify that there are a several species of funnel web spiders. ||||| Six million people die each year from stroke, and 5 million survivors are left with a permanent disability. Moreover, the neuronal damage caused by stroke often triggers a progressive decline in cognitive function that doubles the risk of dementia for stroke survivors. Despite this massive global disease burden, there are no approved drugs for treating the neuronal injury caused to the brain by the oxygen deprivation occurring during an ischemic stroke. The precipitous drop in brain pH resulting from stroke activates acid-sensing ion channel 1a. We show that inhibition of these channels using a “double-knot” spider venom peptide massively attenuates brain damage after stroke and improves behavioral outcomes, even when the peptide is administered 8 h after stroke onset. 
 
 Abstract 
 
 Stroke is the second-leading cause of death worldwide, yet there are no drugs available to protect the brain from stroke-induced neuronal injury. Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and a key mediator of acidosis-induced neuronal damage following cerebral ischemia. Genetic ablation and selective pharmacologic inhibition of ASIC1a reduces neuronal death following ischemic stroke in rodents. Here, we demonstrate that Hi1a, a disulfide-rich spider venom peptide, is highly neuroprotective in a focal model of ischemic stroke. Nuclear magnetic resonance structural studies reveal that Hi1a comprises two homologous inhibitor cystine knot domains separated by a short, structurally well-defined linker. In contrast with known ASIC1a inhibitors, Hi1a incompletely inhibits ASIC1a activation in a pH-independent and slowly reversible manner. Whole-cell, macropatch, and single-channel electrophysiological recordings indicate that Hi1a binds to and stabilizes the closed state of the channel, thereby impeding the transition into a conducting state. Intracerebroventricular administration to rats of a single small dose of Hi1a (2 ng/kg) up to 8 h after stroke induction by occlusion of the middle cerebral artery markedly reduced infarct size, and this correlated with improved neurological and motor function, as well as with preservation of neuronal architecture. Thus, Hi1a is a powerful pharmacological tool for probing the role of ASIC1a in acid-mediated neuronal injury and various neurological disorders, and a promising lead for the development of therapeutics to protect the brain from ischemic injury.
– Almost 6 million people die from a stroke each year, and although scientists aren't recommending spider bites to remedy that, the poison contained in one particular arachnid may fend off stroke-related brain damage, the Guardian reports. In a study published in the PNAS journal, Australian scientists discovered that just a tiny amount of a peptide called Hi1a, found in the venom of the Darling Downs funnel web spider (Hadronyche infensa), was able to cut down on brain damage in rats by 80% if it was given two hours after the rats had suffered a stroke. And the effects were still significant when Hi1a was administered eight hours after the stroke, leading to a 65% reduction. The discovery was made somewhat by accident after researchers had "milked exhaustively" three funnel web spiders they'd gathered in Brisbane to study their toxins. They noticed one peculiar-looking molecule that looked like a mega version of a brain-cell-protecting chemical—so they tested it to see if it might help cells starved of oxygen by strokes. Rats that didn't receive the H1iA "performed very badly" after their stroke, study co-author Glenn King says, while those who did get it were nearly as good as new. "We believe that we have, for the first time, found a way to minimize the effects of brain damage after a stroke," says King, per the Sydney Morning Herald. The researchers warn that the results can't yet be extrapolated to humans and that it's unclear whether the peptide would work in strokes caused by blood vessel ruptures, as well as those caused by blockages. One scientist not involved in the study called it "a very exciting discovery and a very big effect," but cautioned that any practical applications are years away. (Rare snake venom could one day provide humans with pain relief.)