Evaluation of Small-Fiber Polyneuropathy in Youth

青年小纤维多发性神经病的评估

基本信息

批准号：
10674977
负责人：
Anne Louise Oaklander
金额：
$ 63.86万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
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/10674977
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 Trials Collaborations Communities Complement Computerized Medical Record DNA Sequence Alteration Data Development Diabetes Mellitus Diagnosis Disease Distress Elderly Epidemiology Epigenetic Process Etiology Evaluation Examinations and Diagnoses Exertion Family Family member Fiber Fibromyalgia Funding Future Genes Genetic Genetic Risk Genome Genomics Genotype Goals Hereditary Sensory and Autonomic Neuropathies Immune Immunoglobulins Individual 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 Patient Selection Patients Peripheral Nerves Peripheral Nervous System Diseases Persons Pharmacodynamics Phenotype Physicians Polyneuropathy Population Predictive Value Prevalence Probability Procedures Productivity PubMed Public Health Publishing Qualifying Recommendation Registries Reporting Research Research Personnel Risk Safety Sampling Schools Secure Site Skin Source Specificity Standardization 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 diagnostic tool 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

项目摘要

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.

项目概要/摘要这是 R01NS093653 奖项的续签申请，该奖项一直资助奥克兰实验室的研究小纤维神经病是最近公认的一种导致慢性疼痛的周围神经疾病，通常从脚部开始蔓延，难以完成日常活动和胃肠道不适。 2013 年，该团队研究了 41 名儿童和年轻人，出乎意料地报告了大多数儿童和年轻人存在 SFN 的证据。当时，SFN 仅在患有糖尿病、化疗或其他有毒物质暴露以及严重接触的老年人中被发现。实验室发现了一种新的病症——早发性 SFN（eoSFN），它迫使许多人退出。实验室随后报告称，41% 的成年人因学业或工作中断而偏离了生活轨迹。纤维肌痛患者也有 SFN 的客观证据，这意味着全球可能有超过 100,000 名 SFN 患者， R01NS093653 资助他们开发用于收集症状数据的标准化工具（SSS 小纤维症状调查）和检查异常（MAGNET 大众神经病检查工具）和列表 PI 还指导麻省总医院的神经病理学实验室进行筛查潜在原因的最佳血液测试。通过检查患者小腿的微小皮肤活检来测量 SFN 的密度来确认 SFN 诊断小纤维神经末梢并将其与正常的活检进行比较因此实验室建立了神经病变登记处。关系数据库现在包含下载的电子病历以及临床和研究测试来自超过 6500 人的 SFN 评估，目前包括 6394 份活检结果和超过 1000 个 SSS 和 MAGNET。每年增加 1000 多名新患者，PI 也是 NIH 和 FDA 资助的 CONCEPPT 的一部分。专家委员会现已发布 SFN 的第一个正式案例定义，其中包含以下要求：这些需要 SSS、MAGNET 和皮肤已经捕获的特定异常。现在目标 1 建议使用注册参与者加上新患者和健康志愿者来适应。并验证 SSS 和 MAGNET 可供任何医生用于一般医疗用途以及用于儿童。与食品和药物管理局的生物标志物资格计划合作以获得 FDA 裁决目标 3 开始全基因组测试，以提高皮肤活检的质量和准确性。 SFN 的原因和风险研究招募了 CONCEPPT 定义的 SFN 患者并增加了更多内容。通过该实验室的 NeuropathyCommons 网站及其全球合作者 Züchner 博士的迈阿密大学神经遗传学。实验室将分析有资格研究已知和未知基因的基因组，这些基因导致或越来越多的遗传性神经病变得可以治疗，Oaklander 博士帮助发表了该研究 HSAN1 的第一个有效治疗方法最终和未来的目标是追踪大量 SFN 患者和患者。使用安全网络和手机版本的 SSS 和 MAGNET 以及邮寄皮肤活检的家庭。这些将使他们能够绘制 SFN 的症状和自然史，识别新的因果途径和潜力治疗，并跟踪儿童和新治疗的患者以监测长期结果和治疗效果。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neuropathic symptoms with SARS-CoV-2 vaccination.

DOI：
10.1101/2022.05.16.22274439
发表时间：
2022-05-17
期刊：
medRxiv : the preprint server for health sciences
影响因子：
0
作者：
Safavi, Farinaz;Gustafson, Lindsey;Nath, Avindra
通讯作者：
Nath, Avindra

Epidermal Neurite Density in Skin Biopsies From Patients With Juvenile Fibromyalgia.

DOI：
10.3899/jrheum.200378
发表时间：
2021-04
期刊：
The Journal of rheumatology
影响因子：
0
作者：
Boneparth A;Chen S;Horton DB;Moorthy LN;Farquhar I;Downs HM;Lee H;Oaklander AL
通讯作者：
Oaklander AL

Validation of the composite autonomic symptom scale 31 (COMPASS-31) in patients with and without small fiber polyneuropathy.