Rare disease CRC for new therapies and new diagnostics

描述(由申请人提供)：这是一个长期对Rett综合征、Angelman综合征(AS)和Prader-Willi综合征(PWS)感兴趣的机构间研究小组提出的申请，要求建立一个罕见疾病临床研究中心(RDCRC)，该中心将成为拟议的罕见疾病临床研究网络(RDCRN)的一部分。该中心将专注于这三种疾病，期望它们可能在短期内具有有意义的治疗潜力。Rett的具体目标将是在广泛的Rett表型上建立表型/基因型相关性，对广泛的Rett个体进行纵向研究，并对广泛的Rett个体进行生存研究。临床试验可以根据动物模型的研究结果来开发。AS的具体目标是根据基因型对AS患者进行纵向评估，完成正在进行的AS患者叶酸和甜菜碱的双盲安慰剂对照试验，并开发一项后续临床试验，以激活AS患者的父亲UBE3A等位基因。PWS的具体目标是根据基因型进行纵向研究，为临床试验开发参数和工具，测试自闭症特征在UPD中是否比缺失病例更常见，以及合作者的其他想法。在微阵列上使用比较基因组杂交(CGH)的试点项目的目的将是开发一种细胞遗传学测试，该测试将在使用CGH微阵列的单一分析中检测所有与临床相关的大规模缺失和重复。这一新的方法也有可能识别新的缺失和重复综合征。RDCRC将利用休斯顿、波士顿、圣地亚哥、盖恩斯维尔和其他地点的GCR。该中心预计将与贝勒的精神发育迟滞研究中心(MRRC)协同工作。提出了一项广泛的计划，以培训罕见疾病临床研究方面的新研究员。该中心将与国际雷特综合征协会(IRSA)、安杰曼综合征基金会(ASF)和普拉德-威利综合征协会(PWSA)建立积极的联系。该RDCRC的网站为www.imgen.bcm.tmc.edu/RDCM，该网站将扩展为包括关于RETT、PWS和AS的广泛信息。预计RDCRC将扩大到包括最初研究的三种疾病的其他地理位置，预计该中心还可以扩大到包括其他疾病，例如可接受肝细胞基因治疗的先天性代谢错误、可通过酶替代疗法治疗的疾病、电荷关联、色素失禁、Smith-Magenis综合征、XP缺失综合征，以及其他染色体缺失和重复综合征。

DESCRIPTION (provided by applicant): This is an application from an inter-institutional group of investigators with long-standing interest in Rett syndrome, Angelman syndrome (AS), and Prader-Willi syndrome (PWS) to establish a Rare Diseases Clinical Research Center (RDCRC) that would be part of the proposed Rare Diseases Clinical Research Network (RDCRN). The Center will focus on these three disorders with the expectation that they may have near-term potential for meaningful therapy. The specific aims for Rett will be to establish a phenotype/genotype correlation over a broad spectrum of Rett phenotypes, to perform longitudinal studies on a broad sample of individuals with Rett, and to perform a survival study on a broad spectrum of Rett individuals. Clinical trials may be developed based on results of studies of animal models. The specific aims for AS are to conduct a longitudinal assessment of patients with AS according to genotype, to complete the ongoing double-blind, placebo controlled trial of folic acid and betaine in AS, and to develop a follow-on clinical trial for activation of the paternal allele for UBE3A in AS patients. The specific aims for PWS are to conduct longitudinal studies according to genotype, to develop parameters and tools for clinical trials, to test whether autistic features are more frequent in UPD than in deletion cases, and other ideas from collaborators. The aim of a pilot project using comparative genomic hybridization (CGH) on microarrays would be to develop a cytogenetic test that would detect all sizable deletions and duplications of clinical relevance on a single analysis using CGH microarrays. This new methodology would also have the potential to identify new deletion and duplication syndromes. The RDCRC will utilize GCRCs in Houston, Boston, San Diego, Gainesville, and other locations. The Center is expected to function synergistically with the Mental Retardation Research Center (MRRC) at Baylor. An extensive program is proposed for training new investigators in clinical research on rare diseases. The Center will have active affiliation with the International Rett Syndrome Association (IRSA), the Angelman Syndrome Foundation (ASF), and the Prader-Willi Syndrome Association (PWSA). A website for this RDCRC is available at www.imgen.bcm.tmc.edu/rdcm, and this site will be expanded to include a wide range of information for Rett, PWS, and AS. It is anticipated that the RDCRC will expand to include other geographic sites for the three diseases to be studied initially, and it is expected that the Center can also expand to include other disorders, such as inborn errors of metabolism amenable to hepatocyte gene therapy, disorders treatable by enzyme replacement therapy, CHARGE association, incontinentia pigmenti, Smith-Magenis syndrome, Xp deletion syndromes, and other chromosomal deletion and duplication syndromes.