New personalised treatment for peripheral artery disease

Doctor Lana McClements, University of Technology Sydney

Vanguard Grant

Years funded: 2026 - 2027

Peripheral artery disease (PAD) exerts a substantial toll on human well-being, impacting over 2.3 million Australians and >230 million people worldwide, with a higher prevalence and poorer response to treatment among women. PAD prevalence is expected to increase by a staggering 50% in 25 years, accelerating the current $875M costs in health care. PAD can severely compromise the quality of life, impairing mobility and, in severe cases, culminating in limb amputation and death.

Treatments for PAD are limited and mostly symptomatic; endovascular procedures are the least efficacious of all and there are no TGA-approved treatments. Therefore, this is an area of unmet need where novel strategies that can treat PAD, capable of promoting healing and restoring blood flow and oxygen supply, are needed. Outcomes of this project will lead to the development of an effective and innovative PAD treatment through repurposing of novel FKBPL-based therapeutic peptides. These peptides showed excellent safety profile in humans and, in preclinical studies, contribute to stable blood vessel formation in ischemia.

PAD is understudied, underrepresented and underdiagnosed cardiovascular disease. Knowledge gaps exist in understanding the causes, pathophysiology and sex differences.

To address this unmet need, we propose to undertake a series of pioneering experiments that will generate important innovations leading to development of a next generation therapy for PAD:

i) design and validate new FKBPL mimetics with improved pharmacokinetics and efficacy ii) repurpose a safe and novel FKBPL-based therapeutic peptide, AD-01, for stable blood vessel development following ischemia-induced injury in pre-clinical PAD models iii) better understand sex differences in response to FKBPL-based peptide mimetics in preclinical models of PAD iv) decipher the cellular and molecular mechanisms of action of FKBPL and its therapeutic peptides using real-time and advanced 3D microfluidics in vitro models recapitulating PAD that will contribute to 3Rs in animal research v) systematically assess FKBPL-mediated mechanisms and therapeutic potential of FKBPL mimetics in a “proof-of-principle” studies involving human tissues of both sexes.

We will utilise FKBPL transgenic mice, advance 3D microfluidics endothelial dysfunction models and PAD patient tissue unique to our research group, and, to the best of our knowledge, we are the only group in the world who is investigating FKBPL-based therapies for PAD.

This is a first-in-class curative PAD treatment that has a potential to significantly improve the quality of life of men and women living with PAD, preventing disease progression including leg amputations by restoring blood flow and vascular dysfunction.