Growth Factors in Recurrent Aphthous Stomatitis

描述(申请人提供)：复发性口腔炎(RAS)是一种非常常见的原因不明的溃疡性口腔粘膜疾病。对这种非常痛苦的疾病患者溃疡形成的确切病因和机制缺乏了解，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，从而为我们的患者开发更好的药物，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的免疫系统被激活了。然而，对于是什么导致它的激活并最终导致RAS的发展，还没有达成一致意见。现代医学已经发现内分泌和免疫系统之间存在强烈的相互作用。特别是，生长因子，如IGF-1和瘦素，已被证明调节免疫系统和伤口愈合。在两项单独发表的人口研究中，我们发现RAS患病率和这些生长因素的分布与年龄有显着重叠。然而，这些数据并不能直接将单一样本人群中RAS和血清生长因子水平联系起来。我们的总体假设是IGF-1/Leptin途径的上调是RAS患者免疫激活和创面愈合受损的主要来源。我们建议通过对具有全国代表性的数据进行二级统计分析，对这些因素进行详细的个人层面的研究。具体目标1是比较检查时有无RAS的个体的血清IGF-1水平。具体目标2是比较有RAS和无RAS的个体在检查时的血清瘦素水平。我们预计与对照组相比，活动期RAS患者的IGF-1和瘦素水平更高。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溃疡的存在密切相关。这些分析的结果将为R01水平的临床研究奠定基础，这些研究的重点是IGF-1/Leptin途径作为导致RAS形成的主要动力。 公共卫生相关性：复发性口腔炎(RAS；也称为溃烂疮)是一种原因不明的非常常见和痛苦的疾病，主要发生在发育过程中。我们注意到RAS和某些调节伤口愈合的生长因子之间有显著的重叠，这表明这可能是RAS发展的途径。确定导致RAS形成的具体机制将为开发更有针对性的药物打开大门，预计这些药物对患有这种疾病的患者具有更少的副作用和更大的疗效。

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.