Recent developments in targets for ischemic foot disease
Golledge, Jonathan, Thanigaimani, Shivshankar, Barratt, Kristen S., and Fadini, Gian Paolo (2024) Recent developments in targets for ischemic foot disease. Diabetes/Metabolism Research and Reviews, 40 (3). e3703.
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Abstract
Diabetes is a key risk factor for ischaemic foot disease, which causes pain, tissue loss, hospital admission, and major amputation. Currently, treatment focuses on revascularisation, but many patients are unsuitable for surgery and revascularisation is frequently unsuccessful. The authors describe recent research in animal models and clinical trials investigating novel medical targets for ischaemia, including theories about impaired wound healing, animal models for limb ischaemia and recent randomised controlled trials testing novel medical therapies. Novel targets identified in animal models included stimulating mobilisation of CD34+ progenitor cells through upregulating oncostatin M or microRNA-181, downregulating tumour necrosis factor superfamily member 14, or activating the Wingless pathway. Within the ischaemic limb vasculature, upregulation of apolipoprotein L domain containing 1, microRNA-130b or long noncoding RNA that enhances endothelial nitric oxide synthase expression promoted limb blood supply recovery, angiogenesis, and arteriogenesis. Similarly, administration of soluble guanylate cyclase stimulators riociguat or praliciguat or 3-ketoacyl-CoA thiolase inhibitor trimetazidine promoted blood flow recovery. Translating pre-clinical findings to patients has been challenging, mainly due to limitations in clinically translatable animal models of human disease. Promising results have been reported for administering plasmids encoding hepatocyte growth factor or intra-arterial injection of bone marrow derived cells in small clinical trials. It remains to be seen whether these high resource therapies can be developed to be widely applicable. In conclusion, an ever-expanding list of potential targets for medical revascularisation is being identified. It is hoped that through ongoing research and further larger clinical trials, these will translate into new broadly applicable therapies to improve outcomes.
Item ID: | 80381 |
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Item Type: | Article (Research - C1) |
ISSN: | 1520-7560 |
Keywords: | clinical trials, diabetes-related foot disease, ischaemia, mouse models, peripheral artery disease, ulcer |
Copyright Information: | © 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Date Deposited: | 31 Jan 2024 00:40 |
FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100% |
SEO Codes: | 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100% |
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