Bush Tick Breakthrough – Revolutionising Stroke Therapy With Nature's Anti-Clotting Drug
Pictured, from left: The Heart Research Institute's Thrombosis Group lead researcher, Professor Shaun Jackson, with senior research officer in vivo biology, Imala Alwis, and in the background, postdoctoral researcher, biology team Dr Jessica Maclean - assessing the effects of novel anticoagulant leads on blood clot formation and lysis, analysed by confocal microscopy.
Stroke is the second leading cause of death and third leading cause of disability worldwide1, impacting 15 million people globally2 and 60,000 Australians each year. The annual societal cost of stroke is large, estimated to be $6.2 billion in direct financial costs in Australia and a further $26 billion in lost wellbeing and premature mortality.3 These numbers will rise with increasing rates of obesity, diabetes and other known stroke risk factors.
The majority of stroke cases are caused by blood clots restricting blood flow to the brain4, which if not resolved can result in brain damage and death. Therefore, treatment relies on the successful reopening of the blocked artery through administration of intravenous thrombolysis to break up the clot, or mechanical clot removal (thrombectomy). Thrombolysis involves the intravenous delivery of a ‘clot-busting’ drug and is the current standard-of-care. Recombinant tissue plasminogen activator (rtPA) is the only ‘clot-busting’ drug currently approved to treat stroke.
While efficacious, thrombolysis and thrombectomy have inherent drawbacks and in over 30 per cent of cases, damaged blood vessels re-block following treatment of the initial clot and restoration of blood flow.5 This necessitates the additional use of anti-clotting therapy, in a similar manner to the current standard approach to treating heart attack. However, for stroke patients, combined administration of thrombolysis and anti-clotting agents results in unacceptably high rates of life-threatening brain bleeds, offsetting any therapeutic benefits6. As a result, all currently approved anti-clotting drugs are contraindicated for use with rtPA in stroke.
Spearheading an initiative aimed at revolutionising stroke therapy
In response to these challenges, the Heart Research Institute (HRI) and the University of Sydney have spearheaded an initiative aimed at revolutionising stroke therapy. Led by HRI’s Thrombosis Group lead researcher Professor Shaun Jackson, the interdisciplinary team of research scientists and clinicians have identified a naturally occurring anti-clotting agent (AIS109), derived from the saliva of the blood feeding Australian ‘bush tick’. AIS109 exhibits unique anti-clotting properties with minimal bleeding risks. The natural anti-clotting agent holds promising potential to significantly improve the effectiveness and safety of rtPA for stroke treatment, positioning AIS109 as an exceptionally attractive option.
“Combining current antithrombotic agents with either thrombolytic drugs or mechanical thrombectomy, can lead to symptomatic intracerebral haemorrhage in >10 per cent of treated patients. This is where the unique safety profile of our lead anticoagulant peptides has the potential to make a significant difference – reducing bleeding and increasing treatment options and outcomes for stroke patients,” Professor Jackson said.
In 2021, the research team secured a $750,000 grant through the inaugural round of the Targeted Translation Research Accelerator (TTRA) Research Projects opportunity delivered by MTPConnect, alongside invaluable support from TTRA Partner UniQuesti.
With decades of expertise in such fields as peptide medicinal chemistry, pathophysiology of blood clotting and pre-clinical drug development, the research team has worked to enhance the potency of these naturally derived anti-clotting agents, creating new peptide drugs. The two years of funding enabled the research team to successfully reach a key value inflection point in its studies, by refining the native tick derived peptides and discovering two truncated lead drug candidates being progressed towards the clinic.
Encouraging research outcomes secure further funding
Biology Team lead of the Thrombosis Group, Associate Professor Simone Schoenwaelder, said during the funding period they had been able to demonstrate that when combined with thrombolysis, these new peptides, boasted enhanced efficacy and safety profiles.
"The new peptides also demonstrate improved stroke outcomes in preclinical models and have now proceeded to the next stage of development – pharmacokinetic and toxicology testing in animal models, before first-in-human clinical trials,” A/Professor Schoenwaelder said.
These encouraging research outcomes served as a spark to secure a further $7 million in non-dilutive funding from State and Federal Governments. This influx of support heralds a promising future for the discovery platform, empowering the team to capitalise on past successes by expanding its capabilities and resources. With these additional funds, the team will enhance its capacity to scale the lead peptides of AIS109 for toxicological and safety testing to de-risk these novel agents in stroke therapy for future clinical trials.
In addition to the research team’s funding success, the potential for these peptides to transform the stroke therapy landscape was highlighted through broad media coverage throughout the TTRA funding period. This included a story featured in The Australian titled ‘Aussie tick spit breakthrough may be key to clot-busting stroke treatment’ and a dedicated episode of the ABC’s Catalyst science documentary series, ‘Monsters Or Medicine?’, shining a spotlight on the team’s groundbreaking work.
Following the successful completion of its TTRA-funded project ThromBio Holdings Pty Ltd, an Australian biotechnology company based in NSW, is acquiring the licence to further develop these peptides for stroke therapy in collaboration with HRI and the University of Sydney.
Innovative approach holds promise for transforming stroke treatment paradigms
Such strategic partnerships have the ability to advance drug candidates in the company’s pipeline through to late-stage pre-clinical and early clinical stage assets, which positions ThromBio for partnerships with larger pharmaceutical companies which could ultimately bring a new product to market with the goal of improving outcomes for stroke patients worldwide.
ThromBio CEO Peter Bush said: “As a direct result of TTRA outcomes, we have secured significant non-dilutive funds to continue preclinical development of this exciting technology, including the generation of gram quantities of our lead candidates to facilitate pharmacokinetic and maximum tolerated dose studies of the two lead peptides in vivo.”
The journey from identifying a naturally occurring anti-clotting agent in a native species to developing novel peptides for stroke therapy exemplifies the potential of translational research through interdisciplinary collaboration. This innovative approach holds promise for transforming stroke treatment paradigms and enhancing patient outcomes on a global scale.
1.
https://www.who.int/news-room/...
2. https://www.weforum.org/agenda...
3. https://www.deloitte.com/au/en...
4 https://www.stroke.org/en/abou....
5 https://www.neurology.org/doi/...
6. https://www.ahajournals.org/do...
i.
The TTRA program has partnered with specialist organisations to provide translation advice and support to awarded projects. UniQuest provides specialist therapeutic support and is the commercialisation company of the University of Queensland.