Evaluation of small-fiber polyneuropathy in youth

青年小纤维多发性神经病的评估

• 批准号: 10260559
• 负责人: Anne Louise Oaklander
• 金额: $ 64.88万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10260559
• 关键词: 21 year old; Address; Adult; Age; Age Reporting; Analgesics; Award; Biological Markers; Biopsy; Blood Tests; Candidate Disease Gene; Cellular Phone; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Complement; Computerized Medical Record; DNA Sequence Alteration; Data; Data Analyses; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Distress; Elderly; Epidemiology; Epigenetic Process; Etiology; Evaluation; Exertion; Family; Family member; Fiber; Fibromyalgia; Funding; Future; Genes; Genetic; Genetic Risk; Genome; Genomics; Genotype; Goals; Immune; Immunoglobulins; Individual; Institutes; Internet; Knowledge; Leg; Letters; Life; Link; Manuscripts; Maps; Measurement; Measures; Medical; Modeling; Monitor; Names; Natural History; Nerve Endings; Nerve Fibers; Neuropathy; Outcome; Pain; Pain Measurement; Pain Research; Participant; Pathogenicity; Pathway interactions; Patient Care; Patient Recruitments; Patients; Peripheral Nerves; Peripheral Nervous System Diseases; Pharmacodynamics; Phenotype; Physicians; Polyneuropathy; Population; Predictive Value; Prevalence; Procedures; Productivity; PubMed; Public Health; Publishing; Qualifying; Recommendation; Registries; Reporting; Research; Risk; Safety; Sampling; Schools; Secure; Sensitivity and Specificity; Site; Skin; Source; Standardization; Structure; Surveys; Symptoms; Testing; Toxicant exposure; United States Food and Drug Administration; United States National Institutes of Health; Untranslated RNA; Variant; Visit; Withdrawal; Work; Youth; aged; chemotherapy; chronic pain; chronic widespread pain; cohort; density; diagnostic accuracy; early onset; effective therapy; ethnic diversity; evidence base; foot; gastrointestinal; genome wide screen; genome-wide; health disparity; healthy volunteer; improved; lectures; meetings; neurogenetics; neuropathology; painful neuropathy; patient registry; programs; recruit; relational database; research study; response; risk variant; tool; treatment effect; web site; whole genome; young adult

Project Summary/Abstract This is a renewal application for the R01NS093653 award that has been funding the Oaklander lab's research on small-fiber neuropathy. SFN is a recently recognized peripheral nerve illness that causes chronic pain, usually starting in the feet and spreading up, difficulty completing routine activities and gastrointestinal distress. In 2013, the team studied 41 children and young adults, unexpectedly reporting evidence of SFN in most. Until then, SFN was known only in older adults with diabetes, chemotherapy or other toxic exposures and serious diseases. The lab had discovered a new condition–early onset SFN (eoSFN). For many, it forced withdrawal from school or work, derailing young patients' life trajectories. When the lab then reported that 41% of adults with fibromyalgia also had objective evidence of SFN, implying there might be > 100,000 SFN patients globally, R01NS093653 funded them to develop standardized tools for collecting data about symptoms (the SSS small- fiber symptom survey) and exam abnormalities (the MAGNET Mass General Neuropathy Exam Tool) and a list of best blood tests to screen for potential causes. The PI also directs Mass General's neuropathology lab that confirms SFN diagnoses by examining tiny skin biopsies from patients' lower leg to measure the density of small-fiber nerve endings and compare it to biopsies from normal. So the lab built the Neuropathy Registry, a relational database now containing downloaded electronic medical records plus clinical and research testing from >6500 people evaluated for SFN. It currently includes 6394 biopsy results and >1000 SSS and MAGNETs with more than 1000 new patients added yearly. The PI is also part of the NIH and FDA funded CONCEPPT committee of experts now publishing the 1st formal case definition for SFN, with inclusion requirements for research. These require specific abnormalities that are already captured by the SSS, MAGNET, and skin biopsy. Now Aim 1 proposes to use Registry participants plus new patients and healthy volunteers to adapt and validate the SSS and MAGNET for general medical use by any doctor and for use in children. Aim 2 will collaborate with the Food and Drug Administration's Biomarker Qualification Program to obtain an FDA ruling on lab requirements to improve the quality and accuracy of skin biopsy testing. Aim 3 begins whole-genome study of causes and risks for SFN. It recruits Registry patients with CONCEPPT-defined SFN and adds more via the lab's NeuropathyCommons website and its global collaborators. Dr. Züchner's U. Miami neurogenetics lab will analyze the genomes of qualifying participants to study known and unknown genes that cause or increase risk for SFN. More genetic neuropathies are becoming treatable and Dr. Oaklander helped publish the 1st effective treatment for HSAN1. The final and future goal is to track large numbers of SFN patients and families using secure web and cell-phone versions of the SSS and MAGNET and mailed-in skin biopsies. These will allow them to map SFN's symptoms and natural history, identify new causal pathways and potential treatments, and track children and newly treated patients to monitor long-term outcomes and treatment effects.

项目摘要/摘要 这是R01NS093653奖的续签申请，该奖项一直在为奥克兰德实验室的研究提供资金 在小型纤维神经病上。 SFN是最近公认的外周神经疾病，会导致慢性疼痛， 通常从脚开始并扩散，很难完成常规活动和胃肠道困扰。 2013年，该小组研究了41名儿童和年轻人，意外地报告了大多数SFN的证据。直到 然后，仅在患有糖尿病，化学疗法或其他有毒暴露和严重性的老年人中知道SFN 疾病。该实验室发现了一种新的条件 - 早期发作SFN（EOSFN）。对于许多人来说，它迫使退出 从学校或工作中，使年轻患者的生活轨迹脱轨。当实验室报告41％的成年人时 纤维肌痛也有客观的SFN证据，这意味着全球可能有> 100,000名SFN患者， R01NS093653资助了他们开发标准化工具，用于收集有关符号的数据（SSS小型 - 纤维症状调查）和检查异常（磁铁质量一般神经病检查工具）和列表 最佳血液测试以筛选潜在原因。 PI还指导大众一般的神经病理学实验室 通过检查患者下腿的微型皮肤活检以测量的密度来确认SFN诊断。 小纤维神经末日，并将其与正常的活检进行比较。因此，实验室建立了神经病注册表 现在包含下载的电子病历以及临床和研究测试的关系数据库 从> 6500人评估的SFN。它目前包括6394个活检结果以及> 1000 SS和磁铁 每年增加1000多名新患者。 PI也是NIH和FDA资助的Conceppt的一部分 专家委员会现在发布针对SFN的第一个正式案例定义，包含在内的要求 研究。这些需要SSS，磁铁和皮肤已经捕获的特定异常 活检。现在目标1个建议使用注册表参与者以及新患者和健康志愿者适应注册表 并验证SSS和磁铁，以供任何医生一般医疗用途，并用于儿童。 AIM 2意志 与食品药品监督管理局的生物标志物资格计划合作以获得FDA裁决 关于实验室的要求，以提高皮肤活检测试的质量和准确性。 AIM 3开始全基因组 研究SFN的原因和风险。它招募了具有Conceppt定义的SFN的注册表患者，并增加了更多 通过实验室的神经性病变网站及其全球合作者。 Züchner博士的U. Miami神经遗传学 实验室将分析合格参与者的基因组，以研究导致或未知的基因引起或未知的基因 增加SFN的风险。更多的遗传神经病正在变得可以治疗，奥克兰德博士帮助出版了 HSAN1的第一次有效治疗。最终的和未来的目标是跟踪大量的SFN患者和 使用安全的网络和手机版本的SSS和磁铁和邮寄皮肤活检的家庭。 这些将使他们能够映射SFN的符号和自然历史，确定新的因果途径和潜力 治疗，并追踪儿童和新治疗的患者，以监测长期结局和治疗效果。