Growth Factors in Recurrent Aphthous Stomatitis

描述（申请人提供）：复发性口腔溃疡性口腔炎（RAS）是一种非常常见的溃疡性口腔黏膜疾病，病因不明。由于缺乏对患者溃疡形成的确切病因和机制的了解，这种非常痛苦的疾病阻碍了有效治疗方法的发展。为了计划和实施成功的临床试验，从而为我们的病人开发更好的药物，我们必须首先确定这种疾病的原因。大多数科学家都认为，RAS激活了免疫系统。然而，是什么导致了它的激活并最终导致了RAS的发展，目前还没有达成一致意见。现代医学已经确认了内分泌和免疫系统之间的密切联系。特别是，生长因子，如IGF-1和瘦素，已被证明可以调节免疫系统和伤口愈合。在两项独立发表的人口研究中，我们发现RAS患病率和这些生长因子随年龄的分布有显著的重叠。然而，这些数据并没有直接将RAS和单个样本人群中的血清生长因子水平联系起来。我们的总体假设是，IGF-1/瘦素途径的上调是RAS患者免疫激活和伤口愈合受损的主要来源。我们建议通过对全国代表性数据的二次统计分析，对这些因素进行详细的个人水平研究。特异性目的1是比较RAS患者和非RAS患者的血清IGF-1水平。特异性目的2是比较RAS患者和非RAS患者在检查时的血清瘦素水平。我们预计RAS活跃患者的IGF-1和瘦素水平高于对照组。这些结果将提供第一个证据，证明这些生长因子的水平与疼痛性溃疡的存在密切相关。这些分析结果将为关注IGF-1/leptin通路作为RAS形成的主要驱动力的r01水平的临床研究奠定基础。

DESCRIPTION (provided by applicant): Recurrent Aphthous Stomatitis (RAS) is a very common ulcerative oral mucosal disease of unknown etiology. The lack of understanding of the exact etiology and mechanism of ulcer formation in patients afflicted by this very painful condition has hampered the development of effective therapies. In order to plan and implement successful clinical trials leading to the development of better drugs for our patients we must first identify the cause of this disease. Most scientists agree that the immune system is activated in RAS. However, there is no agreement as to what leads to its activation and ultimately to the development of RAS. Modern medicine has identified intense cross-talks between the endocrine and immune system. In particular, growth factors, such as IGF-1 and leptin, have been shown to regulate the immune system and also wound healing. In two separate published population studies we have found a striking overlap in the distributions with age in RAS prevalence and these growth factors. These data, however, do not directly associate RAS and serum levels of growth factors within a single sample population. Our overall hypothesis is that an up-regulation of the IGF-1/leptin pathway is the primary source of immune activation and impaired wound healing in RAS patients. We propose a detailed person-level study of these factors through secondary statistical analyses of nationally representative data. Specific Aim 1 is to compare serum IGF-1 levels in individuals with and without RAS upon examination. Specific Aim 2 is to compare serum leptin levels in individuals with and without RAS upon examination. We expect higher IGF-1 and leptin levels in patients with active RAS vs. controls. These results will provide the first evidence that the levels of these growth factors are closely associated with the presence of painful ulcers. The results of these analyses will create the foundation for R01-level clinical research studies focused on the IGF-1/leptin pathway as the primary driving force leading to RAS formation. PUBLIC HEALTH RELEVANCE: Recurrent Aphthous Stomatitis (RAS; also known as canker sores) is a very common and painful disease of unknown cause that occurs primarily during growth. We have noted a remarkable overlap between RAS and certain growth factors that regulate wound healing, suggesting that this could be the pathway through which RAS develops. The identification of the specific mechanism that leads to RAS formation would open the door to the development of more targeted drugs, expected to have fewer side effects and greater efficacy, for patients suffering from this condition.