Natural History of ABCA4-Related Retinopathies

ABCA4 相关视网膜病变的自然史

• 批准号: 8737692
• 负责人: Brian Brooks
• 金额: $ 1.18万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8737692
• 关键词: Biopsy; Blood specimen; Cells; Clinic; Clinical; Clinical Research; Clinical Trials; DNA; Data Analyses; Diagnostic Imaging; Disease; Drug Formulations; Electrophysiology (science); Electroretinography; Eligibility Determination; Enrollment; Evaluation; Fibroblasts; Future; Generations; Genetic screening method; Genotype; Medical; Medical Genetics; Medical Records; Molecular; Natural History; Ophthalmic examination and evaluation; Optical Coherence Tomography; Outcome; Outcome Measure; Outcome Study; Participant; Pathogenesis; Perimetry; Phase II Clinical Trials; Phenotype; Plasma; Preclinical Drug Evaluation; Protocols documentation; Psychophysiology; Recording of previous events; Recruitment Activity; Research; Research Personnel; Retinal; Retinal Diseases; Sampling; Serum; Skin; Therapeutic; Time; United States National Institutes of Health; Visit; base; cohort; design; in vivo; induced pluripotent stem cell; novel; primary outcome; relating to nervous system; repository; secondary outcome; treatment trial

Design: In this natural history study, participants will be followed for five years. Because three years may be required to enroll 40 participants, this study will last up to eight years. Participants will be recruited through other pre-existing NIH protocols, such as the NEI Evaluation and Treatment Trial (08-EI-0169), the NEI Screening Protocol (08-EI-0102), and the National Ophthalmic Disease Genotyping and Phenotyping Network, Phase II protocol (eyeGENE II, 10-EI-N164), or through referral from an outside clinician after a review of pertinent medical records and genetic testing. All participants will undergo a standardized medical/ophthalmic history and a complete baseline eye examination, including non-invasive electrophysiology (e.g., electroretinography), psychophysiology (e.g., microperimetry, static perimetry), and diagnostic imaging examinations (e.g., optical coherence tomography). The participants will be examined three times over the course of the first year (i.e., baseline examination, Month 6, and Month 12). After the first year, they will return to the NEI clinic on an annual basis for the next four years. This study will require a minimum of seven study visits. Participants may be seen at more frequent intervals at the investigators discretion, depending on the clinical and research situation. Participants will be required to submit a blood sample as part of the study for DNA and serum banking, and they will have the option to provide a 3 mm punch skin biopsy to facilitate research at a cellular level. Outcome Measures: The primary outcome for this study is the establishment of a cohort of participants with ABCA4-related retinopathies, and the secondary outcome is the creation of a repository of plasma, DNA, and skin fibroblast samples from the accrued cohort of ABCA4-related retinopathy participants. Exploratory outcomes for this study include: 1) the formulation of clinical outcome measures for future studies and 2) the acquisition and preliminary analysis of data that may advance our understanding of genotype-phenotype correlations in ABCA4-related retinopathies. Potential exploratory outcomes include: 1) the generation of iPS cells from the skin fibroblast samples, 2) the differentiation of the generated iPS cells into RPE and/or neural retinal cells, and 3) the use of the participant-specific RPE and/or neural retinal cells to perform HTP drug screens to identify novel potential therapeutic compounds. The cells obtained in this protocol may be genetically modified and may be used for in vivo research.

设计：在这项自然历史研究中，参与者将被跟踪五年。由于招募 40 名参与者可能需要三年时间，因此这项研究将持续长达八年。参与者将通过其他现有的 NIH 协议招募，例如 NEI 评估和治疗试验 (08-EI-0169)、NEI 筛查协议 (08-EI-0102) 以及国家眼科疾病基因分型和表型网络， II 期方案（eyeGENE II，10-EI-N164），或在审查相关医疗记录和基因检测后通过外部临床医生的转诊。所有参与者都将接受标准化的医疗/眼科病史和完整的基线眼部检查，包括无创电生理学（例如视网膜电图）、心理生理学（例如微视野检查、静态视野检查）和诊断成像检查（例如光学相干断层扫描）。 参与者将在第一年接受三次检查（即基线检查、第 6 个月和第 12 个月）。第一年后，他们将在接下来的四年里每年回到 NEI 诊所。这项研究将需要至少七次考察访问。调查人员可以酌情更频繁地会见参与者，具体取决于 临床和研究情况。作为 DNA 和血清库研究的一部分，参与者将被要求提交血液样本，并且他们可以选择提供 3 毫米穿孔皮肤活检，以促进细胞水平的研究。 结果测量：本研究的主要结果是建立了一组患有 ABCA4 相关视网膜病的参与者，次要结果是从累积的 ABCA4 相关队列中创建了血浆、DNA 和皮肤成纤维细胞样本的存储库。视网膜病变参与者。本研究的探索性结果包括：1）为未来研究制定临床结果测量；2）采集和初步分析可能促进我们对 ABCA4 相关视网膜病基因型-表型相关性的理解的数据。潜在的探索性结果包括：1）从皮肤成纤维细胞样本中生成 iPS 细胞，2）将生成的 iPS 细胞分化为 RPE 和/或神经视网膜细胞，以及 3）使用参与者特定的 RPE 和/或神经视网膜细胞进行 HTP 药物筛选，以确定新型潜在治疗化合物。在此协议中获得的细胞可以进行基因改造，并可用于体内研究。