Clinical Research Consortium for Spinocerebellar Ataxias

描述（由申请人提供）：本申请涉及广泛挑战领域（04）临床研究和特定挑战主题，04-NS-103临床研究开发联盟，并且部分与07-OD（ORR）-102* 罕见疾病遗传患者登记相关。佛罗里达大学为当地和区域经济做出了巨大贡献。在2008年，UF创造了2,525个工作岗位，最近的研究表明，UF每年为佛罗里达的经济贡献近60亿美元。该大学直接在其主校区雇用约34，000人，并通过用友组织，如食品和农业科学研究所，负责在全州范围内创造74，894个就业机会。目前的应用程序将创造或保留19个工作岗位。本申请的目标是建立一个新的多学科联盟，为未来的临床试验提供基础设施，以测试共济失调疾病治疗干预的安全性和有效性。我们将重点介绍常染色体显性遗传性脊髓小脑共济失调（SCA）1，2，3和6，其发病机制越来越清楚。为了实现这一目标，我们将建立一个协调良好的全国性网络，由具有临床共济失调研究专业知识的医生科学家组成，并将患者支持组织，资助机构和行业整合到该联盟中，该联盟将被称为脊髓小脑共济失调临床研究联盟（CRC-SCA）。CRC-SCA的长期目标是获得启动治疗共济失调的主要临床试验的能力，这些试验基于广泛的自然史数据、来自患者登记研究的大型患者队列、经验证的评级量表（具有更高的灵敏度，可准确检测具有临床意义的结局的微小变化）、有用的生物标志物以及进行统计数据分析的良好能力。此外，它将通过充分利用基于网络的技术，教育患者、家庭、护理人员、医疗保健提供者、政府官员和公众关于治疗干预研究的进展。我们的具体目标是：目标1。为CRC-SCA目标2奠定组织基础。招募患者并获得纵向临床数据，用于未来的临床试验目的3。启动一项试点研究，以确定SCA 1、2、3和6的遗传修饰剂。进行一项初步的I/II期随机双盲安慰剂对照试验，以评估伐尼克兰在SCA患者中的安全性和耐受性。CRC-SCA利用目前现有的临床研究小组，其中包括来自美国的8个机构，建立一个多学科网络，并整合国家共济失调基金会（NAF），鲍勃艾利森共济失调研究中心（BAARC），NINDS和行业（医学Marveric），以实现这些特定目标。我们还将利用美国国立卫生研究院资助的临床和转化研究机构和一般临床研究中心为我们的项目。虽然两年时间不足以实现我们的长期目标，但实现这些具体目标将使CRC-SCA能够建立这样做的机制。因此，CRC-SCA代表了共济失调领域中临床和转化研究的当前关键需求。 公共卫生相关性：脊髓小脑共济失调（SCA）是一种遗传性神经系统疾病，随着时间的推移不断恶化，导致严重残疾或死亡。我们将重点关注SCA的四种亚型，SCA 1，2，3和6，其中研究人员在了解疾病机制方面取得了重大进展，并开始考虑新的治疗方法。我们将建立一个SCA的临床研究联盟（CRC-SCA），这将提供多学科的基础设施，将这些新的治疗思路带到床边。

DESCRIPTION (provided by applicant): This application addresses Broad Challenge Area (04) Clinical Research, and specific Challenge Topics, 04-NS-103 Developing consortia for clinical research, and is also, in part, relevant to 07-OD(ORDR)-102* Rare disease genetic patient registry. The University of Florida contributes substantially to the local and regional economy. In 2008, UF created 2,525 jobs and recent studies have shown that UF contributes nearly $6 billion annually to Florida's economy. The university employs about 34,000 people directly on its main campus and via UF organizations, such as the Institute of Food and Agricultural Sciences, is responsible for the creation of 74,894 jobs statewide. The current application will create or retain 19 jobs. The goal of this application is to establish a new multidisciplinary consortium that provides the infrastructure for future clinical trials to test safety and efficacy of therapeutic interventions for ataxic disorders. We will focus on autosomal dominant spinocerebellar ataxia (SCA) 1, 2, 3 and 6, whose pathogenic mechanisms are becoming increasingly clear. To achieve this goal we will establish a well-coordinated nationwide network of physician scientists with expertise in clinical ataxia research, and integrate patient support organizations, funding agencies and the industry into the consortium, which will be called the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA). The long-term goal of the CRC-SCA is to gain a capability of launching major clinical trials for treatment of ataxia, based on extensive natural history data, large cohort of patients from a patient registries, validated rating scales with increased sensitivity to accurately detect small changes of clinically meaningful outcomes, useful biomarkers, and sound capability to perform statistical data analysis. In addition, it will educate patients, families, caregivers, healthcare providers, government officials and the public about the progress in research toward therapeutic interventions, by taking full advantage of web-based technology. Our Specific Aims are to: Aim 1. Establish the organizational foundations for the CRC-SCA Aim 2. Recruit patients and obtain longitudinal clinical data for future clinical trials Aim 3. Initiate a pilot study to determine genetic modifiers of SCA 1, 2, 3 and 6 Aim 4. Conduct a pilot phase I/II randomized double-blind placebo control trial for safety and tolerability of varenicline in SCA patients. The CRC-SCA takes advantage of a currently existing clinical research group, which involves 8 institutions from the United States, to establish a multidisciplinary network, and integrate the National Ataxia Foundation (NAF), Bob Allison Ataxia Research Center (BAARC), NINDS, and the industry (Medical Marveric) to accomplish these Specific Aims. We will also utilize NIH- funded Clinical and Translational Research Institutes and General Clinical Research Centers for our project. While two years will not be sufficient to achieve our long-term goal, accomplishing these Specific Aims will allow the CRC-SCA to create the machinery to do so. Thus, the CRC- SCA represents a current critical need for clinical and translational research in the field of ataxia. PUBLIC HEALTH RELEVANCE: Spinocerebellar ataxias (SCAs) are inherited neurological diseases which relentlessly worsen over time, leading to severe disability or death. We will focus on four subtypes of SCAs, SCA 1, 2, 3 and 6, in which investigators have made major advances in understanding the disease mechanisms and started contemplating novel treatments. We will establish a clinical research consortium for SCA (CRC-SCA), which will provide multidisciplinary infrastructure to bring these novel treatment ideas to bedside.