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(ORDR)-102*罕见病遗传患者登记相关。佛罗里达大学为当地和地区经济做出了巨大贡献。2008年，佛罗里达大学创造了2525个工作岗位，最近的研究表明，佛罗里达大学每年为佛罗里达经济贡献近60亿美元。该大学在其主校区直接雇用了约34,000人，并通过佛罗里达大学组织，如食品和农业科学研究所，负责在全州创造74,894个工作岗位。目前的申请将创造或保留19个工作岗位。本申请的目的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，以测试治疗性共济失调的干预措施的安全性和有效性。我们将重点关注常染色体显性脊髓小脑性共济失调（SCA） 1,2,3和6，其致病机制越来越清楚。为了实现这一目标，我们将建立一个由具有临床共济失调研究专业知识的医师科学家组成的协调良好的全国网络，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的长期目标是获得开展治疗共济失调的主要临床试验的能力，基于广泛的自然病史数据，来自患者登记册的大量患者，经过验证的评分量表具有更高的灵敏度，可以准确检测临床有意义的结果的微小变化，有用的生物标志物，以及执行统计数据分析的良好能力。此外，它还将通过充分利用网络技术，向患者、家属、护理人员、医疗保健提供者、政府官员和公众宣传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建立组织基础。招募患者并获得纵向临床数据，用于未来的临床试验。启动初步研究，以确定SCA 1、2、3和6的遗传修饰因子。开展一项试验性I/II期随机双盲安慰剂对照试验，研究伐尼克兰在SCA患者中的安全性和耐受性。CRC-SCA利用现有的临床研究小组，包括来自美国的8家机构，建立一个多学科的网络，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（Medical Marveric）来实现这些具体目标。我们也将利用美国国立卫生研究院资助的临床和转化研究所以及一般临床研究中心来进行我们的项目。虽然两年的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代表了当前共济失调领域临床和转化研究的迫切需要。

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.