New research by RCSI University of Medicine and Health Sciences published in Blood journal has identified how a new medicine can help people living with the bleeding disorder von Willebrand disease. The discovery opens the way for more targeted treatments of the condition, which is the most common inherited bleeding disorder in humans.

Von Willebrand disease affects as many as one in 100 individuals. It is caused by a reduced quantity or function of von Willebrand factor in the blood.  

“Because von Willebrand factor has an important role in blood to form clots, patients with von Willebrand disease experience abnormal bleeding episodes, such as heavy menstrual bleeding, nose bleeds, mouth bleeds and bleeding during surgery and childbirth,” explains Dr Alain Chan Kwo Chion, a senior post-doctoral fellow at RCSI’s School of Pharmacy and Biomolecular Sciences and the Irish Centre for Vascular Biology.  

Through a series of experiments, the RCSI team showed how the drug Rondaptivon pegol helps to maintain levels of von Willebrand factor by slowing its clearance from the bloodstream.  

“At the moment, people with von Willebrand disease are treated by increasing von Willebrand factor in the bloodstream through either administering drugs to encourage the release of von Willebrand factor that is stored in cells near blood vessels or by injecting von Willebrand factor into their veins,” explains Dr Chion. “A new drug called Rondaptivon pegol – also known as BT200 – uses a very different approach to increase von Willebrand factor in the blood. BT200 increases the amount of von Willebrand factor by slowing the body from removing the factor from the blood.”  

New therapies

The RCSI researchers set out to investigate how BT200 slows that clearance and keeps levels of von Willebrand factor high. In a series of lab experiments, they showed that BT200 makes it more difficult for immune system cells called macrophages to bind to von Willebrand factor and remove it from the bloodstream.  

They identified a section of von Willebrand factor where macrophages typically bind to remove it from the blood, and showed how BT200 partially interferes with this binding. This means the macrophages cannot remove the factor as quickly, and the factor stays in the bloodstream for longer.  

“These insights highlight how the clearance pathway can be a target for new therapies to help people with von Willebrand disease and other blood conditions,” says Professor James O’Donnell, Professor of Vascular Biology at RCSI’s School of Pharmacy and Biomolecular Sciences and Director of the Irish Centre for Vascular Biology at RCSI, who led the research. 

“Our data supports the concept that targeted inhibition of von Willebrand factor clearance pathways represents a novel therapeutic approach for von Willebrand disease and other blood diseases and disorders such as hemophilia A,” he says.  

“In the case of von Willebrand disease, this novel therapeutic approach may significantly impact the lives of patients who do not respond sufficiently to current treatment or who develop severe side-effects to current treatment.” 

The research, which was supported by a Future (FFP) Award and the US National Institutes of Health, also involved scientists from BAND Therapeutics, who invented the BT200 drug.  

The full paper, published in the prestigious journal Blood, is available here.