Spider venom molecule meets benchmarks to treat heart attack and stroke

 There is a venom library. What the fuck are our stroke researchers doing with this to help with stroke recovery? There is already this out there:

Snake Venom Helps Hydrogels Stop the Bleeding

Intravenous Ancrod for Treatment of Acute Ischemic Stroke

Biting back - snake venom contains toxic clotting factors

 

Snake Venom Could Hold Key To Alzheimer’s Breakthrough

Metrion taps Venomtech’s venom library for ion channel modulator discovery

The latest here:

Spider venom molecule meets benchmarks to treat heart attack and stroke

A spider venom molecule being investigated by a University of Queensland team has met critical benchmarks towards becoming a treatment for heart attack and stroke.

Associate Professor Nathan Palpant and Professor Glenn King from UQ's Institute for Molecular Bioscience have previously shown that the drug candidate Hi1a protects cells from the damage caused by heart attack and stroke.

Dr Palpant said a subsequent study has put the drug through a series of preclinical tests designed to mimic real-life treatment scenarios.

These tests are a major step towards helping us understand how Hi1a would work as a therapeutic – at what stage of a heart attack it could be used and what the doses should be.

We established that Hi1a is as effective at protecting the heart as the only cardioprotective drug to reach Phase 3 clinical trials, a drug that was ultimately shelved due to side effects.

Importantly, we found that Hi1a only interacts with cells in the injured zone of the heart during an attack and doesn't bind to healthy regions of the heart – reducing the chance of side effects."

Dr. Nathan Palpant, Associate Professor, UQ's Institute for Molecular Bioscience

Professor King, who recently won the Prime Minister's Prize for Innovation for developing the world's first insecticides from spider venom, discovered Hi1a in the venom of the K'gari funnel web spider.

"Hi1a could reduce damage to the heart and brain during heart attacks and strokes by preventing cell death caused by lack of oxygen," Professor King said.

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"Our testing and safety studies from independent contract research organisations has provided evidence that Hi1a could be an effective and safe therapeutic."

Infensa Bioscience, a company co-founded by the researchers, raised $23 million in 2022 to develop Hi1a for commercial purposes.

Infensa CEO and UQ researcher, Associate Professor Mark Smythe, said cardiovascular disease is the leading cause of death globally.

"Most deaths from cardiovascular disease are caused by heart attacks and strokes, yet there are no drugs on the market that prevent the damage they cause," Dr Smythe said.

"An effective drug to treat heart attacks would have worldwide impact, providing a breakthrough to improve the lives of millions of individuals living with heart disease."

The research team included Dr Meredith Redd from IMB as well as Dr Melissa Reichelt and Dr Yusuke Yoshikawa from UQ's School of Biomedical Sciences.

The study was published in the world's leading cardiac journal The European Heart Journal.

Source:

University of Queensland

Journal reference:

Redd, M. A., et al. (2023). Acid-sensing ion channel 1a blockade reduces myocardial injury in rodent models of myocardial infarction. European Heart Journal. doi.org/10.1093/eurheartj/ehad793.

Deadly spider venom can help heart attack survivors recover: ‘This could be life-changing’

 Hell, we've known about spider venom possibilities since March 2015 and I bet your stroke hospital HAS DONE NOTHING!

• spider venom (4 posts to March 2015)

Deadly spider venom can help heart attack survivors recover: ‘This could be life-changing’

BRISBANE, Australia — Fear of spiders, or arachnophobia, is one of the most common phobias. According to a new study, however, our eight-legged friends may turn out to be life savers. Researchers from the University of Queensland report that venom from one particular type of spider is the integral ingredient in a new life-saving treatment for heart attack victims.

The spider in question, known formally as the Fraser Island (K’gari) funnel web spider, is considered among the world’s most deadly. Ironically, a molecule extracted from this spider’s venom is being used to produce a new drug candidate capable of both preventing heart attack damage and extending the life of donor hearts used for organ transplants.

Study authors explain that the new drug actually blocks a “death signal” sent from the heart during a heart attack.

“After a heart attack, blood flow to the heart is reduced, resulting in a lack of oxygen to heart muscle,” study co-author Dr. Nathan Palpant, UQ’s Institute for Molecular Bioscience (IMB), says in a university release. “The lack of oxygen causes the cell environment to become acidic, which combine to send a message for heart cells to die. Despite decades of research, no one has been able to develop a drug that stops this death signal in heart cells, which is one of the reasons why heart disease continues to be the leading cause of death in the world.”

The drug candidate, a protein called Hi1a, was tested by exposing beating human heart cells to heart attack stressors. Then, the drug was added to the mix to see if it improved outcomes.

“The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” Dr. Palpant comments.

Spider venom treatment could be major breakthrough for transplant patients

If approved, this new drug would certainly be a game changer: there are currently no drugs available capable of preventing heart attack caused damage.

“This will not only help the hundreds of thousands of people who have a heart attack every year around the world, it could also increase the number and quality of donor hearts, which will give hope to those waiting on the transplant list,” notes Professor Peter Macdonald from the Victor Chang Cardiac Research Institute. “The survival of heart cells is vital in heart transplants — treating hearts with Hi1a and reducing cell death will increase how far the heart can be transported and improve the likelihood of a successful transplant.”

“Usually, if the donor heart has stopped beating for more than 30 minutes before retrieval, the heart can’t be used – even if we can buy an extra 10 minutes, that could make the difference between someone having a heart and someone missing out. For people who are literally on death’s door, this could be life-changing,” he adds.

These findings build off of earlier work by another of the study’s co-authors, Professor Glenn King, who had previously discovered a small protein in the venom of the Fraser Island (K’gari) funnel-web spider capable of improving recovery in stroke survivors.

“We discovered this small protein, Hi1a, amazingly reduces damage to the brain even when it is given up to eight hours after stroke onset,” King says. “It made sense to also test Hi1a on heart cells, because like the brain, the heart is one of the most sensitive organs in the body to the loss of blood flow and lack of oxygen.”

“For heart attack victims, our vision for the future is that Hi1a could be administered by first responders in the ambulance, which would really change the health outcomes of heart disease,” he continues. “This is particularly important in rural and remote parts of Australia where patients and treating hospitals can be long distances apart – and when every second counts.”

These findings can also help in the transfer of donor hearts for cardiac transplantation. The drug/protein looks to be able to facilitate the transport of donor hearts over longer distances, thus increasing the network of both available donors and recipients.

Moving forward, researchers are hoping to begin human clinical trials for both stroke and heart disease in about two to three years.

The study is published in Circulation. 

 

Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a

In rodents, but with ANY BRAINS AT ALL in stroke this would be immediately followed up with human testing. Alas, we have NO BRAINS  in stoke leadership so you, your children and grandchildren will be screwed yet on the next stroke.
http://www.pnas.org/content/114/14/3750.short

Irène R. Chassagnon, Claudia A. McCarthy, Yanni K.-Y. Chin, Sandy S. Pineda, Angelo Keramidas, Mehdi Mobli, Vi Pham, T. Michael De Silva, Joseph W. Lynch, Robert E. Widdop, Lachlan D. Rash, and Glenn F. King

PNAS April 4, 2017 114 (14) 3750-3755; published ahead of print March 20, 2017 https://doi.org/10.1073/pnas.1614728114

1. Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved February 6, 2017 (received for review September 1, 2016)

• Article
• Figures & SI
• Authors & Info
• PDF

Significance

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.

• stroke
• acid-sensing ion channel 1a
• venom peptide
• neuroprotection
• ischemia

Footnotes

• ↵¹To whom correspondence may be addressed. Email: l.rash@uq.edu.au or glenn.king@imb.uq.edu.au.

“We’ve found a molecule that can protect the brain even when it’s given up to eight hours after the stroke.” - spider venom

WHOM is your doctor and stroke hospital contacting to get this into human clinical trials? Or are they all fucking lazy assholes?

WAITING FOR SOMEONE ELSE TO SOLVE THE PROBLEM?

https://qz.com/1109258/the-cure-to-hundreds-of-neurological-diseases-could-be-crawling-outside-your-home/ 
The stroke stuff is really important because there are no drugs for stroke. If you have a stroke now, when you get to the hospital after three or four hours, there’s really nothing that can be done for you. You just have to hope that you recover.
[We’ve found] a molecule that can protect the brain even when it’s given up to eight hours after the stroke. When you have a stroke, the region of the brain where the occlusion occurs loses oxygen. The brain is the biggest consumer of glucose in the body. It burns huge amounts of glucose, and it needs oxygen to do that. When it can’t do that it has to use glycolysis, and the end product of glycolysis is lactate, or lactic acid. Just like a muscle that runs out of oxygen when you’re working out, the brain produces large amounts of lactate after a stroke and so just like your muscle it ends up with lactic acidosis. The brain becomes acidic. We have molecules that stop that process.

More on other stuff they are researching at link 

Venom of a deadly spider holds promising therapeutics against stroke.

No text, video only. Whom is going to take responsibility for getting this tested in humans?
Bet nothing gets done since we have NO STROKE LEADERSHIP OR STRATEGY.
https://www.facebook.com/ScienceNaturePage/videos/1091656927633231/ 

New analysis of spider venom reveals seven promising compounds with the potential to relieve chronic pain

Send your doctor after this to see if this could possibly relieve CPSP.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=150284&CultureCode=en
New research shows that seven compounds of the countless found in spider venom block a key step in the body’s ability to pass pain signals to the brain. The hunt for a medicine based on just one of these compounds, which would open up a new class of potent painkillers, is now a step closer according to new research published in the British Journal of Pharmacology.
Pain that cannot be controlled can ruin people’s lives. One in five people worldwide currently suffer from chronic pain, and existing pain treatments often fail to provide relief. The economic burden is huge, with chronic pain in the USA alone estimated to cost around $600 billion a year, greater than the combined economic cost of cancer, diabetes and stroke.
People sense that part of their body is hurting when nerves from the affected area send signals to the brain through what is called the pain pathway. “A compound that blocks Nav1.7 channels is of particular interest for us. Previous research shows indifference to pain among people who lack Nav1.7 channels due to a naturally-occurring genetic mutation – so blocking these channels has the potential of turning off pain in people with normal pain pathways,” says research team leader Professor Glenn King from The University of Queensland’s Institute for Molecular Bioscience, Australia.
Part of the search for new medicines has focused on the world’s 45,000 species of spiders, many of which kill their prey with venoms that contain hundreds – or even thousands – of protein molecules. Some of these molecules block nerve activity. “A conservative estimate indicates that there are nine million spider-venom peptides, and only 0.01% of this vast pharmacological landscape has been explored so far,” says researcher Dr Julie Kaae Klint. The challenge was to build a research method that could search through this huge number of peptides, looking for the ones that could be useful.
Taking up this challenge, the research team built a system that could rapidly analyse the compounds in spider venoms. Using their novel approach, venoms from 206 species of spider were screened, revealing that 40% of the venoms contained at least one compound that blocked human Nav1.7 channels. Of the seven promising compounds identified, they discovered one that was particularly potent, and also had a chemical structure that suggested it would have high levels of chemical, thermal, and biological stability, which would be essential for administering a new medicine. Together these properties make it particularly exciting as a potential painkiller.
“Untapping this natural source of new medicines brings a distinct hope of accelerating the development of a new class of painkillers that can help people who suffer from chronic pain that cannot be treated with current treatment options,” says Dr Klint. The novel screening approach used to isolate the protein molecules from spider venoms could also be applied to other compounds, opening up hope more widely for new and better medicines.

• Full bibliographic informationFull citation: Seven novel modulators of the analgesic target Nav1.7 uncovered using a high-throughput venoms-based discovery approach. Julie K. Klint, Jennifer J. Smith, Irina Vetter, Darshani B. Rupasinghe, Sing Yan Er1, Sebastian Senff, Volker Herzig, Mehdi Mobli, Richard J. Lewis, Bosmans F, & King GF. BJP. DOI: 10.1111/bph.13081
  URL Upon Publication: doi.wiley.com/10.1111/bph.13081