SBIR Phase II: Orally-dosed Intestinal Coating for the Treatment of Type 2 Diabetes Inspired from Bariatric Surgery

这个小企业创新研究（SBIR）二期项目的广泛影响/商业潜力解决了2700万美国人和全球3亿2型糖尿病（T2D）患者的医疗保健需求。这些患者迫切需要一种安全的治疗方法来重建血糖控制，以加强或取代目前的治疗策略，如二甲双胍和胰岛素，这些策略只能减缓疾病的进展。该建议提供了一种独特的T2D治疗方法，该方法基于口服肠道涂层，模仿减肥手术的有益代谢作用。这种新型治疗方法的潜在商业影响是非常显著的，因为美国糖尿病管理的总成本估计超过2450亿美元，而且还在上升。总体而言，令人震惊的是，五分之一的美国医疗保健资金用于糖尿病患者的护理。因此，主要的保险公司对治疗T2D的替代方法的报销非常感兴趣，从而减轻国家的成本负担。拟议的项目支持进一步开发一种基于减肥手术新见解的全新T2D治疗方法。医学界最近认识到，某些涉及十二指肠排除的减肥手术对葡萄糖耐量具有深远而直接的益处。套筒式医疗设备已经为这种方法提供了临床验证，但这种设备具有侵入性，目前由于安全问题尚未获得批准。研究人员提出了一种非侵入性和安全的口服肠道涂层，有望提供与手术和植入套管相同的效果，但既不需要专家也不需要镇静。该提案描述了基于I期项目的积极结果的体外和体内实验，并推动公司进行人体临床试验。具体的Aim-1是通过评价有限数量的合理结构变化来优化活性先导化合物。具体目标2是在慢性糖尿病动物模型中证明铅制剂的剂量依赖性疗效和安全性。咨询了领先的内分泌学家、胃肠病学家和材料科学家，指导了本提案材料和方法的选择。NSF SBIR II期提案中概述的研究的完成将加速临床转化，使这种新疗法更接近有需要的患者。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project addresses the healthcare needs of the 27 million Americans and 300 million patients globally suffering with type 2 diabetes (T2D). These patients are desperate for a safe treatment that reestablishes glycemic control to augment or replace current management strategies such as metformin and insulin, which only slow the progression of the disease. This proposal provides a unique approach to T2D based on an orally delivered intestinal coating that mimics the beneficial metabolic effects of bariatric surgery. The potential commercial impact of this novel treatment is highly significant as the total estimated cost of diabetes management in the US is upwards of $245 billion, and rising. Overall, an astounding 1 in 5 US health care dollars is used for the care of people with diabetes. Therefore, major insurers are very interested in the reimbursement of alternative approaches for treating T2D, thereby lessening the national cost burden.The proposed project supports the further development of an entirely novel treatment for T2D based on new insights from bariatric surgery. The medical community has recently recognized that certain bariatric procedures involving duodenal exclusion confer profound and immediate benefits in glucose tolerance. Sleeve-type medical devices have provided clinical validation for this approach, but such devices are invasive and not currently approved due to safety issues. The investigators propose a non-invasive and safe orally-delivered intestinal coating which is expected to provide the same effect as surgery and implanted sleeves, but requires neither a specialist nor sedation. This proposal describes in-vitro and in-vivo experiments that build on positive results of the Phase I project, and drive the company towards human clinical trials. Specific Aim-1 is to optimize the active lead compound through evaluation of a limited number of rational structural variations. Specific Aim 2 is to demonstrate the dose-dependent efficacy and safety of lead formulations in a chronic diabetic animal model. Consultation with leading endocrinologists, gastroenterologists, and material scientists has guided the selection of the materials and methods of this proposal. Completion of the studies outlined in the NSF SBIR Phase II proposal will accelerate clinical translation, bringing this novel treatment closer to patients in need.