Disease Mechanisms in Best Disease

最佳疾病的疾病机制

基本信息

批准号：
9310286
负责人：
David M Gamm
金额：
$ 49.15万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9310286
关键词：
Affect Alleles Blindness Calcium Cell Differentiation process Cell Line Cell Therapy Cells Cessation of life Chlorides Clustered Regularly Interspaced Short Palindromic Repeats Codon Nucleotides Complementary DNA Data Degenerative Disorder Disease Electrophysiology (science)Engineering Exhibits Family Functional disorder Genes Genotype Histologic Human Impairment In Vitro Intervention Lesion Liquid substance Mediating Missense Mutation Molecular Mutation Ophthalmoscopes Pathologic Pathology Patients Phagocytes Phenotype Photoreceptors Proteins Series Structure of retinal pigment epithelium Subfamily lentivirinae Testing Time Transcript Viral Visual impairment Vitelliform macular dystrophy autosomal dominant mutation disease phenotype experimental study gene therapy genome editing homologous recombination induced pluripotent stem cell knock-down lentiviral-mediated macula multidisciplinary mutant overexpression public health relevance small hairpin RNA

项目摘要

DESCRIPTION (provided by applicant): Best disease, or vitelliform macular dystrophy, is a human macular degenerative disorder characterized by progressive and irreversible central vision loss. The disease is caused by a host of different (largely missense) mutations in the gene BEST1. Currently there is no treatment or cure for this condition. In this multicenter, multi-PI proposal, we will evaluate the pathophysiology of Best disease using RPE cells derived from induced pluripotent stem cells (iPSCs) from patients with known BEST1 mutations. Preliminary data show that these cells recapitulate at least some the phenotypes of human RPE cells with Best disease. We propose multidisciplinary experiments that will lead to a better understanding of this blinding disease, and that include: determining the pathology of Best disease patient-derived RPE cell chloride conductance and cellular electrophysiology; determining the pathological relationship between different mutations, and between dominant and recessive forms of Best disease; and evaluating gene therapy/genome editing as a potential treatment for Best disease. These important studies will pave the way for new treatments for this disorder.

描述（由申请人提供）：Best 疾病或卵黄样黄斑营养不良是一种人类黄斑变性疾病，其特征是进行性和不可逆的中心视力丧失，目前该疾病是由 BEST1 基因中的许多不同（大部分是错义）突变引起的。在这个多中心、多 PI 提案中，我们将使用源自诱导多能干细胞的 RPE 细胞来评估 Best 疾病的病理生理学。来自已知 BEST1 突变的患者（iPSC）的初步数据表明，这些细胞至少重现了患有 Best 疾病的人类 RPE 细胞的一些表型，这将有助于更好地了解这种致盲疾病，其中包括：确定 Best 疾病患者来源的 RPE 细胞氯电导和细胞电生理学的病理学；确定 Best 疾病的不同突变之间以及显性和隐性形式之间的病理关系，并评估基因治疗/基因组编辑的潜力；这些重要的研究将为这种疾病的新疗法铺平道路。