Gene Therapy for Batten Disease

巴顿病的基因治疗

基本信息

批准号：
7579793
负责人：
RONALD G CRYSTAL
金额：
$ 154.94万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7579793
关键词：
Administrator Advisory Committees Affect Age Animals Ataxia Atrophic Biotechnology Brain Brain region Budgets CLN2 gene Capsid Case Report Form Cations Cells Cessation of life Child Childhood Clinical Clinical Markers Clinical Protocols Clinical Research Clinical Trials Clinical Trials Cooperative Group Code Complementary DNA Congresses Core Facility Data Data Collection Dependovirus Development Disease Doctor of Philosophy Dose Eligibility Determination Enzymes Failure Foundations Future Gene Transfer Genes Genetic Medicine Genotype Goals Grant Human Human Resources Immunity Impaired cognition In Vitro Industry Infantile neuronal ceroid lipofuscinosis Knockout Mice Lysosomal Storage Diseases Mediating Monitor Motor Mutation Myoclonus National Institute of Neurological Disorders and Stroke Nerve Degeneration Nervous system structure Neurologic Operative Surgical Procedures Pathway interactions Phase Phenotype Plasmids Principal Investigator Procedures Production Psyche structure Qualifying Quality Control Rattus Recombinant DNA Regulatory Affairs Reporter Genes Research Ethics Committees Research Personnel Resources Retina Rodent Screening procedure Seizures Serotyping Site Speech Delay Spielmeyer-Vogt Disease Standard Preparations System Technology Toxicology Training Transfection United States Food and Drug Administration United States National Institutes of Health Vegetative States Vision Visual Work Writing adeno-associated viral vector base cellular transduction design effective therapy experimental analysis expression vector gene therapy gene therapy clinical study gene transfer vector good laboratory practice improved in vivo institutional biosafety committee meetings nervous system disorder neuron loss nonhuman primate pre-clinical preclinical study prevent programs retinal neuron scale up tripeptidyl-peptidase I vector

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposal is to carry out the preclinical studies and complete regulatory requirements necessary to initiate a clinical trial using an adeno-associated virus to transfer the human CLN2 cDNA to the brain of children with late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, neurodegenerative lysosomal storage disease. The strategy is based on the concept that persistent expression of the normal CLN2 cDNA in the brain will result in sufficient levels of the CLN2 product tripeptidyl peptidase-I (TPP-I) to slow down or halt neurodegeneration. The specific aims are: Aim 1. Demonstrate that the vector, AAV5cuhCLN2, when administered to the brain of experimental animals will result in sufficient distribution, duration and level of functional TPP-I to slow down or halt the progression of the CNS disease in children with LINCL. Aim 2. Optimize the manufacture of the AAV5cuhCLN2 vector under Good Manufacturing Practice (GMP) conditions and quality control the vector for use in the proof of concept and toxicology studies and in a future clinical study. Aim 3. To develop the toxicology data, clinical protocol and regulatory documents for the clinical study, and gain approval for a study from the Institutional Review Board ORB), Institutional Biosafety Committee (IBC), NIH Office of Biotechnology Activities/Recombinant DNA Advisory Committee (NIH OBA/RAC) and the Food and Drug Administration (FDA). To achieve these aims and to insure that the milestones developed in conjunction with the NINDS staff are met, five teams with expertise in vector production, in vitro and in vivo analyses, experimental animal studies (proof of concept and toxicology), regulatory affairs and overall management will be used. Our objective is to be ready to commence a clinical study, to be developed as the data evolves, at the end of the 5 yr grant period.

描述（由申请人提供）：该提案的目的是进行临床前研究和完整的调节要求，以使用腺相关病毒将人CLN2 cDNA转移到晚期婴儿神经元脂肪肌舒适性（LICKL），致命的，神经脱发性溶解性溶液溶质瘤疾病的儿童的大脑中，进行临床试验。该策略基于这样的概念，即在大脑中正常CLN2 cDNA的持续表达将导致足够水平的CLN2产物三肽基肽酶-I（TPP-I）减慢或停止神经变性。具体目的是：目标1。证明载体AAV5CUHCLN2在实验动物的大脑中给药将导致足够的分布，持续时间和功能性TPP-I水平，以减慢或停止lincl儿童中CNS疾病的进展。 AIM 2。在良好的制造实践（GMP）条件（GMP）条件下优化AAV5CUHCLN2载体的制造，并在概念和毒理学研究证明和未来的临床研究中使用质量控制载体。目的3。为临床研究开发毒理学数据，临床方案和调节文件，并获得机构审查委员会ORB的研究，机构生物安全委员会（IBC），NIH生物技术活动/重组DNA咨询委员会（NIH OBA/RAC）（NIH OBA/RAC）和食品和药物管理（FDA）（FDA）。为了实现这些目标，并确保满足了与Ninds员工共同发展的里程碑，五个在矢量生产，体外和体内分析，实验动物研究（概念和毒理学证明）方面具有专业知识的团队，将使用监管事务和整体管理。我们的目标是准备在5年赠款期结束时开始进行一项随着数据的发展而开发的临床研究。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intra-arterial delivery of AAV vectors to the mouse brain after mannitol mediated blood brain barrier disruption.

DOI：
10.1016/j.jconrel.2014.09.018
发表时间：
2014-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
0
作者：
Foley CP;Rubin DG;Santillan A;Sondhi D;Dyke JP;Crystal RG;Gobin YP;Ballon DJ
通讯作者：
Ballon DJ

Advances in the Treatment of Neuronal Ceroid Lipofuscinosis.