Novel test may transform stroke treatment
Stroke is one of Australia’s biggest killers and a leading cause of disability. Australians are struck down by stroke at a rate of one person every nine minutes, mostly by acute ischaemic stroke (AIS) when blood flow to the brain is interrupted by a clot.
The only drug licensed to remove the offending clot and restore blood flow is tissue plasminogen activator (tPA). However, there is wide variability in the way patients respond to it.
The treatment, which currently has a tight therapeutic time window, restores to health about one in 10 people, but one in 20 people may experience harmful bleeding side-effects. In the worst cases, it can be fatal.
A collaboration led by Professor Robert Medcalf from the Australian Centre for Blood Diseases (ACBD) at Monash University's Central Clinical School, backed by NHMRC funding, will develop new drugs to reduce harmful side effects of the current treatment, and also a novel tool to predict how a patient being treated for AIS will respond to tPA.
The predictive tool, developed in preliminary studies, tests patients’ plasma for a key protein marker called plasmin, which is central to how tPA works, as a surrogate for how any individual is going to be affected by tPA.
Chief Investigator C (CIC) Professor Geoffrey Cloud said this test represents a personalised medicine approach to emergency, time-critical treatment for stroke.
“We can potentially have the ability to predict with a spot of blood whether or not a person is going to be in the normal range of plasmin production and need the standard tPA dose or going to be a ‘super responder’, when it might be dangerous to give them tPA and put them at potential increased risk of bleeding in the brain,” Prof. Cloud said.
“It’s never been done before – it’s a potentially ground-breaking approach,” he said.
The collaboration combines the expertise of CIA Prof Medcalf, an international expert in fibrinolysis (the process that removes blood clots); Prof. Cloud as a clinician and Director of Stroke Services at Alfred Health; CIB Professor Ben Boyd from the Monash Institute of Pharmaceutical Sciences, highly skilled in microfluidics and novel ways of delivering drugs; and 10 other stroke physicians and scientists listed as Associate Investigators on the project, including a group of leading stroke physicians in Barcelona, Spain.
A key part of the project involves validating the predictive test. The researchers will prospectively collect blood samples from people who have thrombolysis (clot-busting treatment) in Australia, combining this with existing patient samples from Barcelona.
“We will do a blinded analysis of the samples to see how well each sample responds to tPA. We can then see if there is a clinical association – did the patient bleed with tPA or did the artery re-open, taking into account a few other clinical variables.
“Ultimately, we will need to make the assay practical,” Prof Cloud said. Ideally the testing will occur in the back of an ambulance, where a prick of blood would be taken that would give medical personnel a ‘traffic light’, red or green, indicating whether to go ahead with tPA treatment or not.
“It’s really exciting in terms of clinical utility and how it might change patient care, particularly as time windows for tPA treatment are increasing and more patients are becoming eligible,” he said.
Prof Medcalf also said that the evaluation of new drugs to reduce side-effects of thrombolysis together with the predictive test was an exciting combination.
“It is also great that this project has engaged many of the leading stroke physicians in Australia and overseas to work towards a common goal,” he said.
See more about the lead researchers' groups:
- Professor Robert Medcalf (CIA): www.monash.edu/medicine/ccs/blood-disease/research/fibrinolysis
- Professor Geoffrey Cloud (CIC): www.monash.edu/medicine/ccs/neuroscience/research/cloud-group