Recent developments in targets for ischemic foot disease.

Area of Science:

• Vascular Biology and Regenerative Medicine
• Diabetology and Metabolic Diseases

Background:

• Diabetes significantly increases the risk of ischaemic foot disease, leading to severe complications like amputation.
• Current revascularisation treatments have limitations, with many patients being unsuitable for surgery or experiencing treatment failure.

Purpose of the Study:

• To review recent research on novel medical targets for treating limb ischaemia, focusing on potential therapeutic strategies beyond traditional revascularisation.
• To explore findings from animal models and clinical trials investigating new approaches for improving blood supply and wound healing in ischaemic limbs.

Main Methods:

• Analysis of pre-clinical research in animal models identifying molecular targets (e.g., CD34+ progenitor cells, specific microRNAs, signaling pathways).
• Review of randomized controlled trials testing novel medical therapies, including growth factors, cell-based therapies, and pharmacological agents.
• Evaluation of challenges in translating animal model findings to human clinical applications.

Main Results:

• Animal models suggest targeting CD34+ cell mobilization, specific microRNAs (miR-181, miR-130b), and pathways like Wingless can enhance vascular recovery.
• Pharmacological agents such as soluble guanylate cyclase stimulators (riociguat, praliciguat) and trimetazidine showed promise in promoting blood flow recovery.
• Early clinical trials with hepatocyte growth factor plasmids and bone marrow-derived cells indicate potential, though scalability remains a concern.

Conclusions:

• An increasing number of potential targets for medical revascularisation are being identified through ongoing research.
• Further investigation and larger clinical trials are necessary to translate these promising findings into broadly applicable therapies for ischaemic foot disease.