From venom to drug
Professor Glenn King researches the medical potential of venom at the University of Queensland. Glenn and his research team discovered a new molecule in the venom of Australia’s K’gari Island funnel-web spider. Called Hi1a, this molecule has potential to become a break-through drug.
Glenn teamed up with heart disease researcher Associate Professor Nathan Palpant to test Hi1a in the laboratory. Their research showed that Hi1a prevents injuries to heart cells during heart attacks.
How it works
‘Scientists often don’t understand why drugs are effective,’ Nathan says. ‘But in the case of Hi1a we were able to identify the drug target that causes cell death during ischemic events.’
When ischemia blocks blood flow to the heart, cells become too acidic. This is a dangerous condition called lactic acidosis. When this condition occurs, the heart tissue activates stress signals.
The stress signals pass through a channel called the acid sensing ion channel 1a (ASIC1a). They act like suicide messages that tell the heart cells to die.
But the Hi1a molecule stops the ASIC1a channel from sending suicide signals to the heart cells. Amazingly, this prevents cell deaths in the heart.
‘If we block the suicide signals using Hi1a, fewer cells die and the heart recovers functionality after the injury,’ Nathan explains.
‘We’re excited by these studies because Hi1a appears to have profound benefits in many preclinical heart injury models. Importantly, our studies show that the drug is also safe,’ says Nathan.
‘We think this could be transformative for patients with heart attacks.’
Supporting the next stage of research translation
Showing that Hi1a works in laboratory tests is just the first step in developing it into a drug.
In 2021, the Medical Research Future Fund supported the research with a grant of $1.5 million. The grant is helping the team undertake the next stage of research translation by:
- testing Hi1a on human hearts damaged by lack of oxygen during transplantation
- testing Hi1a in a pig model of heart attack
- optimising the drug's properties to enhance its potential for clinical translation.
The team will use these studies to get regulatory approval to begin clinical trials on humans.
Optimising Hi1a for clinical trials
Hi1a is a complex biological drug, making it difficult and expensive to manufacture.
‘We are working with companies around the world to find a technique to make Hi1a efficiently and at the lowest cost,’ Glenn says.
The team is also optimising Hi1a for treating stroke patients. This is a more challenging task than treating heart attacks. The molecule’s large size prevents it from passing through the blood into the brain.
‘We aim to miniaturise Hi1a while still retaining its therapeutic effects,’ Glenn explains.
A vision for the future
The research team has also established a new company, Infensa Bioscience. The company raised $23 million in seed funding which they will use to further develop Hi1a into drugs for clinical trials.
Infensa Bioscience is planning one of these Hi1a-related drugs to improve the health of donor hearts. This could increase the number of viable hearts available for transplantation.
Another drug is planned for first responders to give people suffering a heart attack or stroke. The drug could prevent ischemia from damaging the heart or brain. This would especially help people who live in remote areas. These patients suffer more severe injuries because of how long it takes to transport them to hospital.
‘This drug could give people a much better chance of coming through ischemia with a better quality of life,’ Nathan says.
Photo: Australia’s K’gari Island funnel-web spider