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Improved clinical and biologic outcome measures in Aicardi Goutieres Syndrome

改善 Aicardi Goutieres 综合征的临床和生物学结果测量

基本信息

批准号：
9804288
负责人：
Adeline Lucie Vanderver
金额：
$ 14.65万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
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/9804288
关键词：
Address Advocacy Affect Age of Onset Anemia Assessment tool Autoimmune Hepatitis Biological Biological Markers Cardiomyopathies Chronic Clinical Clinical Data Clinical Trials Clinical Trials Design Clinical Trials Network Collaborations Communities Companions Data Data Collection Development Developmental Delay Disorders Disease Disease Progression Endocrine System Diseases Enrollment Ensure Exhibits Fever Future Gene Expression Genes Genotype Goals Heterogeneity Impairment Individual Inflammation Inflammatory Injury Interferons Janus kinase Kidney Lead Measures Modeling Myopathy Natural History Neurologic Organ Outcome Outcome Assessment Outcome Measure Outcome Study Pain Patient Outcomes Assessments Patients Phenotype Pilot Projects Population Production Proxy Pulmonary Hypertension Rare Diseases Readiness Recording of previous events Recurrence Reporting Reverse Transcriptase Inhibitors Severities Severity of illness Signal Transduction Skin Spastic Paraparesis Statistical Models Subgroup Symptoms Testing Therapeutic Therapeutic Intervention Therapeutic Trials Thrombocytopenia Time Treatment Efficacy Variant base clinical predictors cohort data integration design diaries disability disease natural history evidence base functional outcomes genetic signature improved industry partner inhibitor/antagonist instrument kinase inhibitor leukodystrophy novel novel marker novel therapeutics outcome prediction overexpression patient population prospective pseudotoxoplasmosis syndrome rare genetic disorder tool tool development treatment response

项目摘要

ABSTRACT Aicardi Goutières Syndrome (AGS) is a rare genetic disorder of excessive interferon (IFN) production, resulting in severe, systemic inflammatory injury and potentially profound disabilities. Most individuals affected by AGS exhibit some degree of neurologic impairment, ranging from mild spastic paraparesis to severe global developmental delay. Additionally, interferon overexpression results in systemic manifestations and recurrent aseptic fevers with severe, chronic irritability. AGS therapeutic trials are limited by heterogeneous patient populations and the lack of disease-specific outcome measures. In Specific Aim 1, we will characterize clinically distinct AGS subgroups at the time of presentation and assess correlation with longitudinal history. We anticipate the identification of cohorts based on statistically relevant disease features that best predict clinical trajectory and outcome. In Specific Aim 2, we will define a novel AGS rating scale to assess longitudinal change. We hypothesize that application of a disease-specific clinical rating scale at defined time points will more closely correlate with disease progression compared to a daily symptom diary and traditional clinical outcome assessment tool results obtained in Project 1. In Specific Aim 3, we will explore the proportionality between a prospective biomarker, interferon signaling gene (ISG) expression, and clinical outcomes. The expected outcome of these aims is the development of tools for clinical trial readiness in AGS. We will identify clinically distinct subgroups of AGS, design an AGS-specific clinical rating scale, and explore the relationship of ISGs to clinical disease. It is expected that the development of these tools will facilitate clinical trial design, with immediate utilization in this setting.

摘要