肢带型肌营养不良R1型（LGMDR1）的临床试验准备：GRASP联盟研究

Clinical Trial Readiness in Limb Girdle Muscular Dystrophy R1 (LGMDR1): A GRASP Consortium Study.

作者信息

Hunn Stephanie M, Alfano Lindsay N, Jones Aileen, Butler Amanda, Lowes Linda P, Iammarino Megan A, Reash Natalie F, Pietruszewski Lindsay, Sasidharan Sandhya, Currence Melissa, Statland Jeffrey M, Strahler Talia, Will Robert, Wicklund Matthew, Dixon Stacy, Augsburger Renee, Mozaffar Tahseen, Laubscher Katie M, Mockler Shelley R H, Mathews Katherine D, Stinson Nikia, Leung Doris G, Stark Molly M, Horton Rebecca A, Kang Peter B, James Meredith K, Clause Amanda, Weihl Conrad C, Johnson Nicholas E

机构信息

Washington University School of Medicine, St. Louis, Missouri, USA.

The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.

出版信息

Ann Clin Transl Neurol. 2025 Jun;12(6):1179-1186. doi: 10.1002/acn3.70049. Epub 2025 Apr 16.

DOI:10.1002/acn3.70049

PMID:40237364

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12172116/

Abstract

OBJECTIVE

Identifying functional measures that are both valid and reliable in the limb girdle muscular dystrophy (LGMD) population is critical for quantifying the level of functional impairment related to disease progression in order to establish clinical trial readiness in the context of anticipated therapeutic trials.

METHODS

Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 subjects with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each subject completed a battery of clinical outcome assessments (COA), including the North Star Assessment for Limb Girdle-Type Dystrophies (NSAD), 10-m walk/run, and Performance of the Upper Limb (PUL), in addition to several patient-reported outcome measures (PROM).

RESULTS

In this baseline cross-sectional analysis, significant correlations were found between COAs and PROMs, with significant differences in the performance of assessments based on subjects' ambulatory status and genetic variant classification.

INTERPRETATION

The study has determined that the NSAD and other assessments are valid and reliable measures for quantifying the level of disease impairment in individuals with LGMDR1.

摘要

目的

确定在肢带型肌营养不良（LGMD）人群中既有效又可靠的功能测量方法，对于量化与疾病进展相关的功能损害水平至关重要，以便在预期的治疗试验背景下确定临床试验的准备情况。

方法

通过LGMD基因解析与表型评估联盟（GRASP-LGMD），42例LGMDR1患者参与了一项为期12个月的自然史研究，该研究在11个国际地点开展。除了几项患者报告的结局指标（PROM）外，每位受试者还完成了一系列临床结局评估（COA），包括肢带型肌营养不良症北极星评估（NSAD）、10米步行/跑步和上肢功能测试（PUL）。