Clinical Research Consortium for Spinocerebellar Ataxias

点击翻译按钮获取中文摘要

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.