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Developing safer anticoagulants for the treatment of stroke

Heart Research Institute & University of Sydney

Grant:
  • Cardiovascular Senior Researcher Grant
Organ System:
  • Cardiovascular
Date Funded:
  • 22 May, 2020
Chief Investigator/s:
  • Associate Professor Simone Schoenwaelder

Project summary

Towards the development of safer drugs that can improve the clot-busting potential of rtPA.

What is the issue for NSW?

Acute Ischaemic Stroke (AIS) is the third most-common cause of death and a leading cause of disability worldwide. The vast majority (>80%) of strokes are caused by blood clots that block blood flow to the brain. The delivery of treatment for stroke is exquisitely time-sensitive – and only rapid removal of obstructive clot(s) and restoration of blood flow to the brain can prevent permanent brain damage and death.

What does the research aim to do and how?

Simone Schoenwaelder is an Associate Professor at the Heart Research Institute, where her research focus is investigating the biology of platelets – blood clotting cells with a critical role in health and disease. A major part of this focus is to translate discoveries in order to develop innovative therapies for the treatment of cardiovascular diseases including stroke.

A/Professor Schoenwaelder completed her undergraduate Bachelor of Science degree in 1992, receiving first class honours at Monash University in Victoria. Following completion of doctoral studies at Monash University (1996), she spent several postdoctoral years at the University of North Carolina, Chapel Hill (USA) as a National Health and Medical Research Council (NHMRC) CJ Martin Fellow in the Department of Cell Biology and Anatomy, in the laboratory of Professor Keith Burridge.

Returning to Australia in 1999 as an NHMRC RD Wright and Monash University Logan Research Fellow, she joined the Australian Centre for Blood Diseases. In 2015, Simone relocated to her current position at HRI and The University of Sydney. Here, her roles include Associate Director of Research Management and Education at HRI, with a conjoint research title of Associate Professor at Charles Perkins Centre, The University of Sydney (Discipline of Physiology), and honorary visiting scholar at the University of Technology Sydney.

Drugs that degrade the scaffold of the blood clot (fibrin) are currently used to remove dangerous clots and reopen blood vessels. This type of therapy – referred to as intravenous “Thrombolytic therapy” (IVT) – involves the delivery of an artificial (recombinant) version of the protein tissue plasminogen activator (rtPA). Despite being the only approved drug option since 1996, rtPA has significant limitations which undermine its effectiveness, and cause significant risk of life-threatening bleeding in the brain. t-PA remains the mainstay of stroke treatment globally, and yet is only administered to 10-13% of all stroke patients, less than half of these achieving a good therapeutic outcome.

The identification of safer drugs that can improve the clot-busting potential of rtPA would represent a major advance in the treatment of stroke. The team have found that a naturally occurring anticlotting protein which demonstrates promising anticlotting properties with minimal bleeding. Their studies will determine whether this protein is a safe anticlotting drug that can be used with rtPA to increase the removal of blood clots using a novel preclinical stroke model. These studies have the potential to not only improve the quality of stroke treatment in general, but also to allow access to safer stroke therapies for those in regional and remote areas.