Retrospective assessment of clinical global impression of severity and change in GM1 gangliosidosis: a tool to score natural history data in rare disease cohorts

作者：Connor Lewis, Jean M. Johnston, Sílvia Zaragoza Domingo, Gilbert Vézina, Precilla D’Souza, William A. Gahl, David Adams, Cynthia J. Tifft, Maria T. Acosta · 发表于：Orphanet Journal of Rare Diseases · 年份：2025 · DOI：10.1186/s13023-025-03614-6 · 被引用次数：11 · 研究领域：Lysosomal Storage Disorders Research、Peripheral Neuropathies and Disorders、Glycosylation and Glycoproteins Research

BACKGROUND: Clinical trials for rare diseases pose unique challenges warranting alternative approaches in demonstrating treatment efficacy. Such trials face challenges including small patient populations, variable onset of symptoms and rate of disease progression, and ethical considerations, particularly in neurodegenerative diseases. In this study, we present the retrospective clinical global impression (RCGI) severity and change (RCGI-S/C) scale on 27 patients with GM1 gangliosidosis, a post hoc clinician-rated outcome measure to evaluate natural history study participants as historical controls for comparisons with treated patients in a clinical trial. METHODS: We conducted a systematic chart review of 27 GM1 gangliosidosis natural history participants across 95 total visits. RCGI-S was assessed at the first visit and rated 1 (normal) to 7 (among the most extremely ill). Each subsequent follow-up was rated on the RCGI-C scale from 1 (very much improved) to 7 (very much worse). We demonstrate scoring guidelines of both scales with examples and justifications for this pilot in GM1 gangliosidosis natural history participants. The convergent validity of the RCGI scales was explored through correlations with magnetic resonance imaging (MRI) and the Vineland Adaptive Behavioral Scales. RESULTS: (1) = 18.6, p < 0.001). Baseline RCGI-S scores also strongly correlated with Vineland adaptive behavioral composite scores taken at the same visit (r(14) = -0.72; 95% CI [-0.93, -0.17], p...