Wednesday, February 5, 2025
2/5/2025
Project Summary/Abstract Peripheral artery disease (PAD) and small vessel disease (SVD) are the consequences of damage to the endothelial cells that line all vessels, leading to inadequate skin perfusion, end-organ failure, and limb damage. This damage is prevalent in the diabetic patient population where nearly 50% suffers from PAD and SVD. Numerous studies describe the difficulties of diagnosing vascular disease in diabetic patients, either due to limited access to the cost-prohibitive Transcutaneous Oximetry (TcPO2), lack of accuracy in limb blood flow evaluation using Ankle Brachial Index (ABI), or the high risk of kidney damage with the use of invasive angiography. The proposed effort addresses this unmet need by offering a simple, inexpensive, and effective device ideal for widespread clinical use to detect and follow the course of PAD and SVD. The expected socioeconomic impacts of clinical adoption of the proposed technology include improvement in patient quality of life by delaying or preventing the development of debilitating disease and a decrease in patient care costs. Our diagnostic system utilizes hydrogen sulfide (H2S), a newly described endothelium-derived vasodilator, that decreases with the onset of endothelial damage and dysfunction. Importantly, normal production of H2S is essential for endothelial function, for improving recovery from muscle ischemia, and to mitigate damage from myocardial and kidney infarction. The technology, Transdermal Arterial Gasotransmitter Sensor (TAGS™), employs an innovative gas-phase detector which noninvasively measures trace levels of H2S emitted from the skin as a measure of vascular health in the skin. During a NHLBI-funded Phase II SBIR research effort, TAGS™ measurements were carried out in human subjects to assess local vascular and microvascular health in healthy individuals, asymptomatic T2D patients, and symptomatic T2D patients with limb-threatening wounds undergoing lower-extremity revascularization surgery. It was found that TAGS™ signals correlate inversely with atherosclerotic and cardiovascular risk score, ASCVD, and with HgbA1C and LDL/HDL ratio (i.e., the biomarkers of diabetes). The results also reveal that PAD in diabetes decreases the bioavailability of H2S in the lower extremity (leg) skin of patients with diabetes so that TAGS™ readings can assess the severity of skin microvascular disease. The proposed CRP pre-clinical study is intended to engage more clinicians to test the TAGS™ methodology against other measures of vascular health and to increase the size of each cohort to provide appropriate power for statistical evaluation. Successful completion of the CRP effort by meeting our Specific Aims is expected to lead to Phase IIB clinical studies.
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