Mechanisms of adverse gastrointestinal events during oral immunotherapy

口服免疫治疗期间胃肠道不良事件的机制

• 批准号: 10365516
• 负责人: Benjamin L. Wright
• 金额: $ 18.99万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-21 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365516
• 关键词: Address; Adverse effects; Allergic; Allergic Disease; Allergy to peanuts; Antibodies; Applications Grants; Arizona; Asthma; Atopic Dermatitis; Award; Basal Cell Hyperplasia; Basic Science; Bioethics; Biological Markers; Biology; Biometry; Blood; CCL26 gene; Caring; Cell Adhesion Molecules; Cellular Immunology; Characteristics; Chemotactic Factors; Chronic; Clinic; Clinical; Clinical Immunology; Clinical Research; Clinical Trials; Collaborations; Data; Development; Diagnosis; Disease; Edema; Endoscopic Biopsy; Environment; Eosinophilia; Eosinophilic Esophagitis; Eosinophilic Gastrointestinal Disease; Epithelial; Esophagus; Event; Exposure to; Extracellular Space; FDA approved; Food; Food Hypersensitivity; Functional disorder; Funding; Goals; Health; Hour; Hypersensitivity; Iatrogenesis; IgE; Immune Tolerance; Immune response; Immunity; Immunologics; Immunology; Individual; Interleukin-13; Interleukin-4; International; Internships; Knowledge; Lead; Life; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Milk; Milk Hypersensitivity; Monitor; Nose; Outcome; Parents; Pathogenesis; Patient Care; Patients; Peripheral Blood Mononuclear Cell; Placebos; Production; Proteomics; Randomized; Request for Applications; Research; Research Design; Research Personnel; Research Proposals; Research Technics; Research Training; Risk; Safety; Sampling; Signal Transduction; Symptoms; Testing; Th2 Cells; Tissues; Training; Training Support; Translating; Translational Research; United States National Institutes of Health; Universities; Vascular Cell Adhesion Molecule-1; career; career development; clinical practice; cytokine; desensitization; design; double-blind placebo controlled trial; eosinophil; eosinophilic inflammation; experience; food antigen; gastrointestinal; gastrointestinal symptom; immunotherapy clinical trials; improved; inflammatory marker; insight; minimally invasive; novel; oral immunotherapy; patient oriented research; peripheral blood; placebo controlled trial; polyposis; prevent; professor; programs; prospective; response; side effect; skills; treatment strategy

ABSTRACT This K23 award application requests support for the career development of Dr. Benjamin Wright, Assistant Professor in the Division of Allergy, Asthma and Clinical Immunology at Mayo Clinic Arizona. The candidate’s overall goal is to become an independent, clinician-investigator and improve the health of individuals with eosinophilic esophagitis (EoE) and food allergy through patient-oriented research. This award will provide the training and support needed to accomplish this goal. Specifically, this proposal will enable Dr. Wright to accomplish the following short-term career goals: (1) acquire training in methods and design of clinical studies and trials in food allergy; (2) develop skills in basic/translational research techniques; (3) develop professional skills necessary to lead a translational research team; and (4) gather preliminary data and biospecimens for a subsequent R01 application and establish an independent research program in food allergy and eosinophilic gastrointestinal disorders. Oral immunotherapy (OIT) is an emerging treatment for food allergy. Although most patients can be successfully desensitized with OIT, many develop gastrointestinal side effects including EoE. EoE is a chronic allergic condition associated with severe esophageal dysfunction. The specific goals of the research proposal are to examine the mechanisms underlying the gastrointestinal side effects of OIT and to develop a novel treatment strategy to prevent them. To accomplish this, we will perform a sub-study of a placebo-controlled trial in patients with milk allergy treated with milk OIT with or without dupilumab. During the trial, we will serially monitor eosinophilic inflammation, markers of esophageal barrier dysfunction, and immune responses in peripheral blood and in the esophagus. To support Dr. Wright’s career development, he will acquire skills in cellular immunology and complete a basic science internship focusing on cutting-edge proteomic analysis of clinical samples. In addition, he will complete formal didactic coursework in clinical research study design, biostatistics, and bioethics. Dr. Wright has assembled a mentoring committee comprised of international experts in food allergy, EoE, proteomics, eosinophil biology, and type 2 immunity uniquely suited to address the hypotheses set forth in this proposal and guide Dr. Wright’s career development. This proposal combines the strength of the research environment at Mayo Clinic and an ongoing collaboration with Stanford University that provides an ideal setting to pursue the aforementioned training and research goals. At the conclusion of this program, Dr. Wright will have the skillset and experience required to transition to independence and lead a translational research team. Successful completion of this project will likely provide a major and sustained impact on the care of patients with food allergy by providing critical insights into the pathogenesis of food allergy and EoE.

抽象的 该K23奖项申请要求支持Benjamin Wright博士的职业发展，助理 亚利桑那州梅奥诊所的过敏，哮喘和临床免疫学教授。候选人的 总体目标是成为独立的，临床评估者，并改善 通过以患者为导向的研究，嗜酸性粒细胞炎（EOE）和食物过敏。该奖项将提供 实现这一目标所需的培训和支持。具体而言，该建议将使赖特博士能够 完成以下短期职业目标：（1）获得临床研究方法和设计的培训 和食物过敏的试验； （2）发展基础/翻译研究技术的技能； （3）发展专业人士 领导转化研究团队所需的技能； （4）收集初步数据和生物测量 随后的R01应用，并在食品过敏和嗜酸性粒细胞中建立独立的研究计划 胃肠道疾病。口服免疫疗法（OIT）是一种新兴的食物过敏疗法。虽然大多数 患者可以通过OIT成功脱敏，许多人会产生包括EOE在内的胃肠道副作用。 EOE是一种与严重的食管功能障碍有关的慢性过敏疾病。特定目标 研究建议是研究OIT胃肠道副作用的基础机制和 制定一种新颖的治疗策略来防止它们。为此，我们将执行 接受牛奶过敏患者的安慰剂对照试验，接受或不用二脂肪的牛奶OIT治疗。在 试验，我们将连续监测嗜酸性注射，食管屏障功能障碍的标志和免疫 外周血和食道的反应。为了支持赖特博士的职业发展，他将 获得细胞免疫学的技能，并完成专注于尖端的基础科学实习 临床样品的蛋白质组学分析。此外，他将完成临床的正式教学课程 研究研究设计，生物统计学和生物伦理学。赖特博士已经组建了一个心理委员会 累积食品过敏，EOE，蛋白质组学，嗜酸性粒细胞生物学和2型免疫培训方面的国际专家 非常适合解决该提案中提出的假设并指导赖特博士的职业 发展。该建议结合了梅奥诊所研究环境的强度和正在进行的 与斯坦福大学的合作，提供了理想的环境，以追求合理的培训和 研究目标。在该计划的结论结束时，赖特博士将拥有所需的技能和经验 过渡到独立并领导转化研究团队。成功完成该项目将 通过提供关键，可能会对食物过敏患者的护理产生重大持续的影响 对食物过敏和EOE的发病机理的见解。