Promoting Research in PLS: Current Knowledge and Future Challenges

促进 PLS 研究：当前知识和未来挑战

基本信息

批准号：
9756640
负责人：
HIROSHI MITSUMOTO
金额：
$ 1.09万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9756640
关键词：
Affect Applications Grants Australia Biological Biological Markers Canada Child Clinical Clinical Sciences Clinical Trials Collaborations Diagnosis Diagnostic Disabled Persons Disease Disease Progression Electrophysiology (science)Europe Funding Future Genetic Goals Guidelines Health care facility Hispanics Impaired cognition Individual International Investigation Knowledge Life Long-Term Care for Elderly Measures Minority Mitochondria Molecular Genetics Motor Neuron Disease Motor Neurons National Institute of Neurological Disorders and Stroke Neurobiology Outcome Measure Paper Patients Pharmaceutical Preparations Phenotype Philadelphia Physicians Positron-Emission Tomography Primary Lateral Sclerosis Publishing Rare Diseases Readiness Registries Reporting Research Research Personnel Schedule Scientist Speech Symptoms Time Woman cognitive function cost ethnic diversity experience frontotemporal lobar dementia-amyotrophic lateral sclerosis genetic analysis improved innovation knowledge base meetings men motor disorder neglect neuroimaging neuropathology neurophysiology novel diagnostics programs prospective racial and ethnic racial minority response sound symposium

项目摘要

Primary lateral sclerosis (PLS) is the rarest form of sporadic motor neuron disease (MND), affecting only upper motor neurons. Although distinct from ALS in that survival is not an immediate concern, PLS is a relentless disease that causes life-long, progressive and severe motor dysfunction. Due to its extreme rarity, PLS has been largely neglected and seldom investigated systematically in a large number of patients. In fact, PLS cases have never been included in any clinical trials in ALS. In addition, current diagnostic criteria require a waiting period of 3 to 4 years before PLS can be diagnosed, which is extremely frustrating for patients and their physicians. In short, our knowledge base for PLS is largely limited, and systematic research has been scanty to date. To improve upon this reality, we propose to hold a highly scientific, international conference on PLS. Most ALS experts agree that PLS holds a key to understanding the disease mechanisms of MNDs, particularly ALS. The organizing committee, which consists of 3 women and 3 men of diverse ethnic/racial origins, proposes to hold a R13 conference on May 3rd and 4th, 2019, immediately before the AAN annual meeting at the Philadelphia Airport Marriott. More than 35 speakers and moderators will participate, representing 30% women, ethnic/racial minorities, and 11 international investigators. All of these individuals, in one way or another, specialize in PLS and have published related scientific papers. The conference will include discussions on the clinical spectrum of PLS and MNDs that mimic it, cognitive impairment which is prevalent in PLS, electrophysiology including cortical hyperexcitability, neuroimaging changes, genetics that can identify definable diseases among PLS phenotypes, biological biomarkers particularly emerging lipidomics and mitochondrial abnormalities, measuring PLS disease progression including potential new outcome measures, and clinical trials in PLS. The keynote speech by Ian Mackenzie, MD, FRCPC, will be on “Neuropathological and Biological Views on PLS, ALS, and FTD.” A panel discussion will be devoted to (1) Revising PLS Diagnostic Criteria, for which we aim to establish practical and effective criteria and (2) Establishing an International PLS Registry. The PLS Registry will encourage future international collaborations and broader access to patients with this rare disease, thus enabling rigorous scientific investigations. The conference format is innovative, characterized by brief presentations that will allow time for extensive, general discussion among the attendees. We will invite young investigators who wish to specialize in PLS or at least MND research. The inclusion of women and minorities in particular is especially important as the field lacks Black and Hispanic representation. We will publish at least one paper on newly developed diagnostic criteria. Our proposed conference will incite international collaborations and effective future research in PLS, including successful clinical trials. After this conference, PLS will no longer be considered a neglected disease.

原发性侧索硬化症 (PLS) 是散发性运动神经元疾病 (MND) 中最罕见的形式，仅影响上上部尽管与 ALS 的不同之处在于生存不是当务之急，但 PLS 是一种无情的治疗。 PLS 是一种导致终生、进行性和严重运动功能障碍的疾病。事实上，PLS 在很大程度上被忽视并且很少对大量患者进行系统研究。病例从未被纳入任何 ALS 临床试验中。此外，目前的诊断标准需要符合 ALS 的标准。诊断 PLS 之前要等待 3 至 4 年，这对患者及其家人来说是极其令人沮丧的简而言之，我们对 PLS 的知识基础非常有限，系统研究也很少。迄今为止，为了改善这一现实，我们建议举办一次高度科学的 PLS 国际会议。大多数 ALS 专家都认为 PLS 是理解 MND 疾病机制的关键，特别是 ALS. 组委会由来自不同种族/种族的 3 名女性和 3 名男性组成，建议于 2019 年 5 月 3 日至 4 日在 AAN 年会之前召开 R13 会议超过 35 名演讲者和主持人将参加，占 30%。女性、少数族裔/种族以及 11 名国际调查员所有这些人，以一种方式或方式。另一位专注于 PLS 并发表了相关科学论文。关于 PLS 和模仿它的 MND 的临床谱的讨论，认知障碍是常见于 PLS、电生理学（包括皮质过度兴奋性）、神经影像学变化、遗传学可以识别 PLS 表型中可定义的疾病，特别是新兴的生物标志物脂质组学和线粒体异常，测量 PLS 疾病进展，包括潜在的新进展 PLS 的结果测量和临床试验将由 Ian Mackenzie 医学博士、FRCPC 发表主题演讲。 “关于 PLS、ALS 和 FTD 的神经病理学和生物学观点。” (1) 修订 PLS 诊断标准，旨在建立实用有效的标准；(2) 建立国际 PLS 注册中心 PLS 注册中心将鼓励未来的国际合作。以及更广泛地接触患有这种罕见疾病的患者，从而能够进行严格的科学研究。会议形式具有创新性，其特点是简短的发言，以便有时间进行广泛的、一般性的讨论我们将邀请希望专门研究 PLS 或至少是的年轻研究人员。由于该领域缺乏，女性和少数族裔的纳入尤其重要。我们将发表至少一篇关于新制定的诊断标准的论文。我们提议的会议将促进 PLS 领域的国际合作和有效的未来研究，包括这次会议之后，PLS将不再被认为是一种被忽视的疾病。