New clot-busting drug may improve treatment for stroke patients

L-R: Professor Christoph Hagemeyer and Dr Be'eri Niego have

published a study investigating a new drug for blood clots.

by Anne Crawford

A team of Monash University researchers has demonstrated that an innovative drug that removes blood clots improves the outcomes of acute ischaemic stroke and has a promising safety profile. 

The study, led by Professor Christoph Hagemeyer and Dr Be’eri Niego from the Australian Centre for Blood Diseases (ACBD), showed the potential of their new clot-busting agent ‘SCE5-scuPA’ in mouse stroke models.

The findings were published in ‘Blood Advances’ late last month.

Ischaemic stroke is caused when a blood vessel supplying blood to the brain is obstructed by a clot and accounts for 80 percent of all types of stroke. It is one of the top five leading causes of death for Australian men and women. The burden of disease of stroke extends beyond the high mortality rate – up to 50% of all stroke survivors remain permanently disabled. 

First author Jason Palazzolo (pictured, left) investigated the SCE5-scuPA drug, which he thought could avoid several shortfalls of t-PA, the only FDA-approved clot-buster medication currently available to stroke patients. The research was part of Mr Palazzolo’s doctoral project supported by Australian Rotary Health and Rotary District 9830. 

Australian Rotary Health Chairman, Mr Kevin Shadbolt OAM said, “We are delighted that a very successful outcome has been achieved with the help of a PhD scholarship funded by Australian Rotary Health and Rotary in Tasmania. Congratulations to Jason and the entire team working on this important project.”

“When blood clots form in the brain, it is a medical emergency that requires the clot to be urgently dissolved to restore blood supply and minimise the extent of permanent brain damage,” Mr Palazzolo said. “Unfortunately, although t-PA is often effective, it sometimes triggers serious bleeding complications that can be more dangerous than the stroke itself,” he said.

“Clearly, there is a clinical need to offer stroke patients new and improved treatment options in order to increase the likelihood of their survival and reduce their disability after stroke.”

The new drug candidate works by fusing two proteins, a ‘clot-targeting’ antibody (termed SCE5) and another clot-dissolving enzyme, Urokinase (scu-PA). “The antibody binds activated platelets that are present exclusively in thrombi and delivers the intended clot-dissolving activity specifically to where it is needed most,” Mr Palazzolo said. “In contrast, t-PA may reach its clot target, but will arriveal so at other undesired destinations and inflict side-effects. In other words, by incorporating a targeting antibody into our drug design, we reduce the likelihood of serious complications whilst also improving the efficiency of thrombolytic (clot-dissolving) therapy,” he said.

Most importantly, the study showed that SCE5-scuPA effectively minimised the extent of brain damage and improved the neurological deficit following stroke. Additionally, it demonstrated that SCE5-scuPA presented with favourable safety outcomes, including a reduction of dangerous intracranial bleeding side-effects.

Said Professor Hagemeyer: “With these findings, we are one step closer towards offering stroke patients a new drug that will improve their quality of life.” 

Dr Niego said that, “moving forward, we hope to continue demonstrating the promise of SCE5-scuPA in additional stroke models and see this drug ultimately entering the clinical testing phase.”

Palazzolo JS, Ale A, Ho H, Jagdale S, Broughton BR, Medcalf RL, Wright DK, Alt K, Hagemeyer CE, Niego B. Platelet-targeted thrombolysis for treatment of acute ischemic stroke. Blood Advances. 2022 Apr 28.  doi: 10.1182/bloodadvances.2021006691. Online ahead of print. PMID: 35482909  https://pubmed.ncbi.nlm.nih.gov/35482909/