Transdermal H2S Sensing Device for Monitoring Peripheral Artery Disease

项目概要/摘要 外周动脉疾病（PAD）和小血管疾病（SVD）是内皮细胞损伤的后果 所有的血管都是这样，这两种情况都会导致皮肤灌注不足以及终末器官和肢体损伤。它在糖尿病患者中普遍存在， 近50%的患者人群患有PAD和SVD。拟议的努力解决了未得到满足的需要， 在该高危人群中诊断PAD和SVD。许多研究描述了诊断动脉疾病的困难 在糖尿病患者中，包括血管钙化的高风险，这导致ABI高估肢体血流量 测量和漏诊的部分闭塞。尽管皮肤灌注的重要作用， 由于缺乏常规筛查方案和需要， 昂贵的诊断设备和训练有素的技术人员。这凸显了发展的重大机遇 简单，廉价的协议，定期筛查受试者皮肤灌注风险因素足够早， 糖尿病视网膜病变、神经病变、肢体缺血、脑血管疾病、冠状动脉疾病 血管疾病和肾病。创建一种在变化可逆的情况下检测血管疾病的方法将： 1)通过延迟或预防终末器官损伤的发展来改善患者的生活质量;以及2）减少患者 护理费用。所提出的方案利用硫化氢（H2S），一种新描述的内皮源性血管扩张剂， 随着内皮疾病的发生而降低，内皮疾病是大多数PAD和SVD病例的根本原因。此外，正常 H2S水平有利于预防内皮功能障碍，改善肌肉缺血的恢复， 减轻心肌梗塞的损害。目前还没有一种非侵入性的方法来精确测量血浆 H2S和少数现有技术需要专门的设备和熟练的技术人员。我们提出的技术， 透皮气体传感器（TAGS ™）采用创新的气相检测器， 血浆H2S水平。在STTR第一阶段可行性研究中，Exhalix和新墨西哥州大学团队开发并 使用实验室版本的TAGS进行初步的动物研究，其中生理相关的正常和 在雄性Sprague-Dawley大鼠中经皮检测到H2S的血浆水平降低。在拟议的SBIR阶段 II更新研究，我们打算继续开发先进的原型的TAGS。这些原型将是 在广泛的受试者中进行验证和确认，包括健康和糖尿病动物和人类受试者 与医学院和中心经验丰富的医生科学家合作，对男女进行研究 转化和临床科学。我们预计，在第二阶段成功开发和验证TAGS将 导致IIB期临床研究和该技术的商业化。

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, both leading to inadequate skin perfusion and end-organ and limb damage. It is prevalent in diabetic patient population in which nearly 50% suffers from PAD and SVD. The proposed effort addresses an unmet need for early diagnosis of PAD and SVD in this high-risk group. A number of studies describe the difficulties in diagnosing arterial disease in diabetic patients, including the high risk of vascular calcification, which leads to overestimates of limb blood flow by ABI measurements and missed diagnosis of partial occlusions. Despite the important role of skin perfusion, it is seldom detected or even tested for in its early stages due to the lack of routine screening protocols and the requirement for expensive diagnostic equipment and trained technicians. This highlights the significant opportunity for development of a simple, inexpensive protocol to routinely screen subjects with skin perfusion risk factors early enough that would allow more effective treatment options for diabetic retinopathy, neuropathy, limb ischemia, cerebral vascular disease, coronary vascular disease and nephropathy. Creating a way to detect vascular disease at a point where changes are reversible will: 1) improve patient quality of life by delaying or preventing the development of end organ damage; and 2) decrease patient care costs. The proposed protocol utilizes hydrogen sulfide (H2S), a newly described endothelium-derived vasodilator that decreases with the onset of endothelial disease, the underlying cause of most PAD and SVD cases. Furthermore, normal levels of H2S are beneficial for preventing endothelial dysfunction, for improving recovery from muscle ischemia and in mitigating damage from myocardial infarction. There is currently no non-invasive method to accurately measure plasma H2S and the few existing techniques require specialized equipment and skilled technicians. Our proposed technology, the transdermal gasotransmitter sensor (TAGS™), employs an innovative gas-phase detector which noninvasively measures plasma levels of H2S. In the STTR Phase I feasibility study, the Exhalix and University of New Mexico team developed and used a laboratory version of TAGS to perform preliminary animal studies in which physiologically relevant normal and reduced plasma levels of H2S were transdermally detected in male Sprague-Dawley rats. During the proposed SBIR Phase II renewal studies, we intend to continue the development of advanced prototypes of TAGS. These prototypes will be verified and validated across a broad cross-section of subjects, including healthy and diabetic animal and human subjects of both sexes, in collaboration with experienced physician scientists at the School of Medicine and the Center for Translational and Clinical Sciences. We anticipate that successful development and validation of TAGS during Phase II will lead to Phase IIB clinical studies and commercialization of the technology.