Photo-responsive thrombin inhibitors enable precise control of localised antithrombotic therapy

The Cardiovascular-protective Signalling and Drug Discovery Group, led by Dr Xuyu Liu, will be conducting a collaborative research project entitled “Photo-responsive thrombin inhibitors enable precise control of localised antithrombotic therapy” with the Ferrier Research Institute of the Victoria University of Wellington (VUW), New Zealand.

Stroke is a leading cause of death and disability in New Zealand and globally, but there is currently only one approved drug treatment for stroke, called rTPA. Previous studies have revealed that anticoagulants can substantially improve the efficiency of rTPA, but they pose a high risk of life-threatening bleeding. This bleeding consequence is ascribed to the indiscriminate inhibition of all roles of thrombin in our circulatory system, the key enzyme in blood clotting, thrombosis and stroke.

Dr Liu’s research will address this shortfall by investigating the transformation of a direct thrombin inhibitor into a photo-responsive therapy for stroke, with the aim to precisely control local anticoagulation using two-photon excitation lasers. It will also provide proof-of-concept information on the utility of this photo-pharmacology system in the treatment of thrombosis and stroke for the first time.

The computational modelling and drug screening in this project will be conducted by Dr Wanting Jiao, who is based at the Ferrier Research Institute of VUW. The project will also involve collaboration with Dr Kai Chen, who will employ world-class spectroscopy techniques and laser facilities for the development of photo-anticoagulant therapy at the Robinson Research Institute of VUW. This collaborative research team aims to develop a cutting-edge, much needed technological platform to create light-controllable drug molecules enabling rapid, non-invasive treatment of stroke. They are also combining the PROteolysis TArgeting Chimera discovery platform established at the Heart Research Institute with femtosecond laser technology to accelerate the development and screening of next generation PROTAC molecules specific for stroke and thrombosis.

“This project has the potential to develop safer treatment strategies for ischaemic stroke,” says Dr Liu. “It also has the capacity to inspire new drug discovery strategies for cardiovascular disease more broadly.”