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）：肌萎缩性侧面硬化症（ALS）是一种毁灭性和神秘的疾病，无法治愈。单一批准的可用药物，riluzole，只会减慢疾病的进展。在过去的20年中，基于各种假设开发的近30种潜在药物已受到广泛的尝试，但这是没有成功的。另一方面，动物模型，分子生物学和神经科学的令人难以置信的进步导致了许多家族性ALS的许多遗传原因，并在ALS中产生了许多令人兴奋的假设。然而，我们对ALS的发病机理和原因的了解仍然存在明显的赤字。因此，如果我们要理解并有效治疗这种疾病，我们需要进一步研究ALS患者的疾病机制和引起的原因。我们坚信，患者本身可能存在这个谜团的关键。但是，研究ALS患者会带来许多挑战，因为1）ALS相对较少（每100,000人口1至2例），2）鉴于其迅速发展，诊断后的研究时间很少，3）通常在成年后期被诊断出患者，很少有直系亲属进行研究，而4个）进入中枢神经系统组织的访问程度很高。尽管存在这些局限性和巨大的方法论挑战，但ALS医师和医师科学家仍处于直接研究ALS的原因和发病机理的最佳位置。此外，我们不仅需要寻找创造性和创新的方法来调查这种疾病，而且还需要与基础科学家作为亲密伴侣合作。因此，我们建议举行一次会议，以激发ALS中的临床或以患者为导向的研究。我们专门针对：1）将ALS的医生，医师科学家和基础科学家聚集在一起，讨论一个集中的主题，临床研究（不是临床试验）； 2）回顾ALS发病机理和原因的当前状态，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，其中大多数适合临床研究； 3）鼓励医生与基础科学家合作，以考虑开发临床研究的可行性，目的是发现ALS的原因和发病机理。此外，我们将讨论必须克服的方法论和资金问题，以推动临床研究向前发展。 4）在大型神经病学杂志中以补充剂或白皮书的形式发表会议的结果和建议。会议将旨在允许开放思想交流，并有望制定未来发展非常活跃的临床研究的策略。当务之急是医生和科学家意识到，比以往任何时候都更需要在ALS中进行这种合作。我们坚信，这次会议将是找到发病机理和原因的一步，最终是这种可怕疾病的治愈方法。 公共卫生相关性：肌萎缩性侧索硬化症（ALS）是最破坏性的神经系统疾病之一，无法治愈。它的发病机理和原因尚未确定。我们提出了一次NIH ALS会议，在该会议上，专门研究ALS的医师和基础科学家将聚集在一起，讨论如何促进和激发临床研究以找到未来ALS的发病机理和原因。这将是导致ALS治疗的重要一步。