A Prospective Longitudinal Observational Study of a Patient With Hutchinson-Gilford Progeria Syndrome: Establishing Natural History Data for the Development of AAV-Cas13-Based RNA-Targeting Gene Therapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Longitudinal change (Baseline vs Year 1/2/3) in molecular, cardiovascular, skeletal, and clinical severity biomarkers in one HGPS patient (LMNA p.G608G)
研究概览
简要总结
This study is a prospective, non-interventional, single-patient observational study following one patient with Hutchinson-Gilford Progeria Syndrome (HGPS), a rare disease that causes rapid, premature aging, over a 3-year period without any therapeutic intervention. The main purpose of this study is to track disease-related biomarkers over time - through physical measurements, cardiac and vascular ultrasound, bone age and bone density scans, cognitive testing, and quality-of-life assessments, along with blood tests (a total of 4 research blood draws, 3ml each) - in order to establish baseline natural history data that will support the future development and evaluation of an RNA-targeting gene therapy (based on AAV-Cas13 technology) for this condition.
详细描述
HGPS natural history observation cohort
Prospective, non-interventional, longitudinal follow-up of 1 genetically confirmed HGPS patient (LMNA c.1824C>T, p.G608G) over 4 timepoints (Baseline, Year 1, Year 2, Year 3, ±1 month window) Molecular biomarker profiling: progerin mRNA/protein, lamin A/C ratio, p21 (CDKN1A), endothelial dysfunction panel (ICAM-1, VCAM-1, MCP-1, eNOS), inflammatory cytokine panel (IL-1β, TNF-α, CRP, IL-6, IFN-γ), innate immunity/atherosclerosis panel (TLR4, ox-LDL, PAI-1) via RT-PCR and ELISA on PBMC and serum Cardiovascular assessment: echocardiography (diastolic function, LVEF, global longitudinal strain), carotid-femoral pulse wave velocity, carotid echodensity and intima-media thickness, ECG, ankle-brachial index Skeletal and growth assessment: anthropometry, DEXA (bone mineral density, body composition), range-of-motion measurement, whole spine X-ray Neurocognitive and functional assessment: age-appropriate IQ testing (K-WISC-V/K-WPPSI-IV), neurological exam, Progeria Severity Score, PedsQL, ADL evaluation Research blood sampling: EDTA 3ml × 4 timepoints (total 12ml)
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A Hutchinson-Gilford Progeria Syndrome (HGPS) patient genetically confirmed by LMNA gene testing (c.1824C>T, p.G608G)
排除标准
- •not applicable
结局指标
主要结局
Longitudinal change (Baseline vs Year 1/2/3) in molecular, cardiovascular, skeletal, and clinical severity biomarkers in one HGPS patient (LMNA p.G608G)
时间窗: From September 2026 to December 2029
1. Molecular Biomarkers * PBMC mRNA: Progerin (ratio), lamin A/C (ratio), p21 (ratio), ICAM-1 (ratio), VCAM-1 (ratio), eNOS (ratio), TLR4 (ratio), PAI-1 (ratio) * Serum: MCP-1 (pg/mL), IL-1β (pg/mL), TNF-α (pg/mL), IL-6 (pg/mL), IFN-γ (pg/mL), CRP (mg/L), ox-LDL (U/L) 2. Cardiovascular: LVEF (%), diastolic function (\[E/e'\], ratio), strain (\[GLS\], %), PWV (m/s), carotid echodensity (gray-scale median, units), cIMT (mm), ECG (\[QTc\], ms), ABI (ratio). 3. Skeletal/Growth: height (cm), weight (kg), head circumference (cm), weight gain (kg/month), ROM (degrees), MMT (points), BBS (points), DEXA BMD (g/cm²), spine X-ray (degrees). 4. Clinical/QoL: QoL (points), ADL (points), Progeria Severity Score (points). 5. Laboratory/Safety: CBC (\[hemoglobin, g/dL; WBC, ×10³/µL; platelets, ×10³/µL\]), AST/ALT/ALP (U/L), bilirubin/BUN/Cr (mg/dL), eGFR (mL/min/1.73 m²), Na/K/Cl (mmol/L), lipids (mg/dL), IGF-1/IGFBP-3 (ng/mL), BP (mmHg), pulse (beats/min), RR (breaths/min), temperature (°C).
次要结局
未报告次要终点
研究者
MinYoung Kim, MD, PhD
Professor, Department of Rehabilitation Medicine, CHA Bundang Medical Center
Bundang CHA Hospital