|Dr Justin Hamilton with one of his students, |
Natasha Setiabakti (BMedSc(Hons)).
Published in Nature Communications, the study led by Monash researchers has uncovered a unique approach to prevent platelet function, responsible for forming blood clots.
Blood clots are the cause of heart attacks and most strokes, which are the most common cause of death and disability in the world.
Dr Justin Hamilton, Head of the Platelet & Megakaryocyte Cell Biology Lab in the Australian Centre for Blood Diseases (ACBD) at Monash University, said drugs that prevented platelet function were the leading approach for heart attack and stroke prevention. However, many patients do not respond to current therapies.
“Our research has discovered that if we block a particular enzyme involved in platelet formation then blood clots literally disintegrate before our eyes. One of the most interesting aspects of these findings is that the clot-stopping approach we’ve discovered here is different to how all current drugs work.
“Current drugs such as aspirin block the signals that instruct platelets to form a clot, whereas our discovery rearranges the way that the cell is built – stopping it from doing its job and forming a clot.”
Using a mouse model, the group has discovered that the PI3KC2α enzyme controls the creation of the membrane structure of platelets, rendering the cells much less effective at blood clot formation.
Dr Hamilton said, “Normal platelet cells are smooth discs carrying a special payload which only gets activated when the cells are needed to form a blood clot. The payload is membrane which can be rapidly extruded to form spikes, thereby increasing their membrane surface area by about 100%. They effectively turn into burrs, which readily clump and mesh together to form a clot.
“When we blocked PI3KC2α function, we found that the platelets were hyperactive when initially binding and sticking, but were unstable in this binding. The reason for the clots breaking up is that although the platelets are still carrying their membrane to turn themselves into these burrs, the structure is not organised properly and this changes how accessible the reserve membrane is to the cell."
Dr Hamilton said that new drugs blocking this enzyme would have the potential to improve heart attack and stroke prevention to help those patients who are resistant to existing therapies.
The team is now working on developing such drugs and testing whether they might be useful as a preventive treatment for heart attack and stroke patients.