Assessment of Neurological Deterioration in Subjects with LINCL

LINCL 受试者神经功能恶化的评估

• 批准号: 8325940
• 负责人: DOUGLAS J BALLON
• 金额: $ 6.73万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325940
• 关键词: 4 year old; Age; Brain; CLN2 gene; Categories; Cessation of life; Child; Clinical; Clinical Research; Code; Complementary DNA; Data; Data Set; Dependovirus; Deterioration; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Disease Progression; Future; Gene Transfer; Genotype; Goals; Lead; Locales; Lysosomal Storage Diseases; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Mutation; Natural History; Nerve Degeneration; Neurologic; Neurological status; Neuronal Ceroid-Lipofuscinosis; Normal Range; Patients; Peptide Hydrolases; Quality Control; Quality of life; Questionnaires; Recruitment Activity; Symptoms; Ventricular; Visit; Water; age related; brain volume; gray matter; imaging modality; infancy; morphometry; novel; tripeptidyl-peptidase I; white matter

Late infantile ceroid lipofuscinosis (LINCL) is a rare, rapidly progressing lysosomal storage disease. The rareness of the patients as well as the possibility of non-uniform progression depending on genotype mean that limited data is available that delineates the natural history of disease progression. The primary focus of this study is to use clinical rating scales and magnetic resonance imaging methods to define the natural history of LINCL and to provide objective and sensitive surrogates for neurological status and for the assessment of the impact of experimental treatments in children with LINCL. To achieve this goal we have 3 aims: (1) Recruit children with LINCL and perform serial neurological assessments and MRI studies; (2) Using this data, expand the spectrum of existing quantitative MRI parameters and derive normal ranges and correlate with neurological status and specific mutations; and (3) Extract additional parameters from MRI data including volumes of brain substructures, local metabolite levels by magnetic resonance spectroscopy and local diffusion weighted imaging. Together, these parameters will be applicable to future clinical studies of novel therapies for LINCL, and should be transferable to other neurological lysosomal storage diseases.

晚期婴儿蜡质脂褐质沉着症（LINCL）是一种罕见的、进展迅速的溶酶体贮积病。患者的稀有性以及取决于基因型的不均匀进展的可能性意味着描述疾病进展自然史的可用数据有限。本研究的主要重点是使用临床评定量表和磁共振成像方法来定义 LINCL 的自然史，并为神经系统状态提供客观和敏感的替代指标，并评估实验治疗对 LINCL 儿童的影响。为了实现这一目标，我们有 3 个目标：(1) 招募 LINCL 儿童并进行系列神经学评估和 MRI 研究； (2) 利用这些数据，扩展现有定量 MRI 参数的范围，推导出正常范围，并与神经状态和特定突变相关联； (3) 从 MRI 数据中提取附加参数，包括大脑亚结构的体积、通过磁共振波谱和局部扩散加权成像的局部代谢物水平。总之，这些参数将适用于 LINCL 新疗法的未来临床研究，并且应该可转移到其他神经性溶酶体贮积病。