Rare disease CRC for new therapies and new diagnostics

描述（由申请人提供）：这是一份来自机构间研究小组的申请，他们对Rett综合征、Angelman综合征（AS）和prder - willi综合征（PWS）长期感兴趣，希望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。该中心将重点关注这三种疾病，并期望它们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Rett个体的广泛样本进行纵向研究，并对Rett个体进行广泛的生存研究。临床试验可以根据动物模型的研究结果进行。针对AS的具体目的是根据基因型对AS患者进行纵向评估，完成正在进行的叶酸和甜菜碱在AS中的双盲安慰剂对照试验，并开展AS患者UBE3A父本等位基因激活的后续临床试验。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频繁，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到所有具有临床相关性的相当大的缺失和重复。这种新方法也有可能发现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gcrc。该中心预计将与贝勒大学的智力迟钝研究中心（MRRC）协同工作。提出了一项广泛的计划，培训罕见病临床研究方面的新研究人员。该中心将与国际Rett综合征协会（IRSA）、Angelman综合征基金会（ASF）和Prader-Willi综合征协会（PWSA）保持积极的联系。该RDCRC的网站可在www.imgen.bcm.tmc.edu/rdcm上找到，该网站将扩展到包括Rett， PWS和AS的广泛信息。预计RDCRC将扩展到包括最初研究的三种疾病的其他地理位置，并且预计该中心还可以扩展到包括其他疾病，如适合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，CHARGE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.