NIH ALS Conference: Clinical Research to Find the Pathogenesis and Cause of ALS

NIH ALS 会议：寻找 ALS 发病机制和原因的临床研究

• 批准号: 8129353
• 负责人: HIROSHI MITSUMOTO
• 金额: $ 2.5万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8129353
• 关键词: Adult; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Biological Markers; Cessation of life; Characteristics; Clinical; Clinical Research; Clinical Trials; Collaborations; Development; Diagnosis; Disease; Disease Progression; Environmental Risk Factor; Epidemiologic Studies; Epigenetic Process; Failure; Familial Amyotrophic Lateral Sclerosis; Family member; Fostering; Funding; Funding Agency; Future; Genetic; Glare; Human; Inherited; International; Investigation; Journals; Knowledge; Lead; Left; Methodological Studies; Modeling; Molecular Biology; Molecular Genetics; Mus; Mutate; Neuraxis; Neurology; Neurosciences; Paper; Paralysed; Pathogenesis; Patients; Pharmaceutical Preparations; Physicians; Population; Positioning Attribute; Problem Solving; Publishing; Recommendation; Research; Research Personnel; Respiratory Failure; Riluzole; SOD1 gene; Scientist; Skeletal Muscle; Suggestion; Testing; Time; Tissues; Transgenic Mice; Uncertainty; United States National Institutes of Health; Variant; Work; base; design; effective therapy; genetic epidemiology; human disease; improved; innovation; interest; knowledge of results; lifestyle factors; meetings; nervous system disorder; patient oriented research; success; symposium

DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is a devastating and enigmatic disease with no cure. The single approved, available medication, Riluzole, only modestly slows disease progression. Nearly 30 potential medications, developed based on diverse hypotheses, have been extensively tried in the past 20 years, but this has been without success. On the other hand, incredible progress in animal models, molecular biology and neuroscience has led to the identification of a number of hereditary causes of familial ALS and generated many exciting hypotheses in ALS. Nevertheless, there is still a glaring deficit in our knowledge of the pathogenesis and cause of ALS. Consequently, if we are to understand and effectively treat this disease, we need to further investigate the disease mechanisms and cause in our ALS patients. We strongly believe that the key to this mystery is likely to exist in the patients themselves. However, studying patients with ALS poses many challenges because 1) ALS is relatively rare (1 to 2 cases per 100,000 population), 2) given its rapid progression, there is little time for research after diagnosis, 3) patients are generally diagnosed late in adulthood, leaving few immediate family members for study, and 4) access to the central nervous system tissue is highly limited. Despite these limitations and tremendous methodological challenges, ALS physicians and physician-scientists are still in the best position to study the cause and pathogenesis of ALS directly in patients. Further, we need not only to find creative and innovative ways to investigate this disease, but also, to work with basic scientists as close partners. Therefore, we propose to hold a conference to energize clinical or patient-oriented research in ALS. We specifically aim to: 1) bring ALS physicians, physician-scientists and basic scientists together to discuss a focused topic, clinical research (not clinical trials); 2) review the current status of the pathogenesis and cause of ALS including clinical characteristics, biomarkers, epidemiology, and genetic and epigenetic studies, most of which are amenable to clinical research; 3) encourage physicians to collaborate with basic scientists in order to consider the feasibility of developing clinical research with the aim of discovering the cause(s) and pathogenesis of ALS. Further, we will discuss methodological and funding issues that must be overcome in order to move clinical research forward; and 4) publish the results and recommendations from the conference as a supplement or as a white paper in a major neurology journal. The meeting will be designed to allow for the open exchange of ideas, and will hopefully work out strategies for developing very active clinical research in the future. It is imperative that physicians and scientists realize that, more than ever before, there is a serious need for such collaboration in ALS. We strongly believe that this meeting will be a step forward to finding the pathogenesis and cause(s), and eventually, the cure for this dreaded disease, ALS. PUBLIC HEALTH RELEVANCE: Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological diseases with no cure. Its pathogenesis and cause are not yet established. We propose an NIH ALS Conference in which physicians and basic scientists, who both specialize in ALS, will come together and discuss how to facilitate and energize clinical research to find the pathogenesis and cause of ALS in the future. This will be an important step to lead to the cure for ALS.

描述（由申请人提供）：肌萎缩侧索硬化症（ALS）是一种毁灭性且神秘的疾病，无法治愈。单一批准的可用药物利鲁唑只能适度减缓疾病进展。近 30 种基于不同假设开发的潜在药物在过去 20 年中已被广泛尝试，但尚未成功。另一方面，动物模型、分子生物学和神经科学方面取得的令人难以置信的进展，已经确定了家族性 ALS 的许多遗传原因，并产生了许多关于 ALS 的令人兴奋的假设。尽管如此，我们对 ALS 的发病机制和病因的了解仍然存在明显缺陷。因此，如果我们要了解并有效治疗这种疾病，我们需要进一步研究 ALS 患者的疾病机制和病因。我们坚信，解开这个谜团的关键很可能存在于患者本身。然而，研究 ALS 患者面临许多挑战，因为 1) ALS 相对罕见（每 100,000 人中有 1 至 2 例），2) 由于其快速进展，诊断后几乎没有时间进行研究，3) 患者通常在成年晚期才被诊断，几乎没有直系亲属可供研究，4) 中枢神经系统组织的接触非常有限。尽管存在这些局限性和巨大的方法学挑战，ALS 医生和医生科学家仍然处于直接研究患者 ALS 病因和发病机制的最佳位置。此外，我们不仅需要找到创造性和创新性的方法来研究这种疾病，而且还需要与基础科学家作为密切的合作伙伴进行合作。因此，我们建议召开一次会议，以激发 ALS 的临床或以患者为导向的研究。我们的具体目标是：1）将 ALS 医生、医生科学家和基础科学家聚集在一起讨论一个重点主题：临床研究（而非临床试验）； 2）回顾ALS发病机制和病因的现状，包括临床特征、生物标志物、流行病学以及遗传和表观遗传学研究，其中大部分适合临床研究； 3) 鼓励医生与基础科学家合作，考虑开展临床研究的可行性，以发现 ALS 的病因和发病机制。此外，我们将讨论为推进临床研究而必须克服的方法和资金问题； 4) 将会议的结果和建议作为补充材料或白皮书发表在主要神经病学期刊上。这次会议旨在允许公开交流想法，并有望制定出未来发展非常活跃的临床研究的策略。医生和科学家必须认识到，在 ALS 领域比以往任何时候都更需要这种合作。我们坚信，这次会议将在寻找发病机制和原因以及最终治愈这种可怕的疾病 ALS 方面向前迈出一步。 公众健康相关性：肌萎缩侧索硬化症 (ALS) 是最具破坏性的神经系统疾病之一，无法治愈。其发病机制和原因尚未确定。我们提议召开 NIH ALS 会议，专门研究 ALS 的医生和基础科学家将齐聚一堂，讨论如何促进和激励临床研究，以找到未来 ALS 的发病机制和病因。这将是治愈 ALS 的重要一步。