Validity of insole-derived spatiotemporal and center-of-pressure metrics in ambulatory Duchenne muscular dystrophy and spinal muscular atrophy

Abstract Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are rare, childhood-onset neuromuscular diseases (NMDs) characterized by progressive muscle weakness that frequently leads to loss of ambulation. Although several approved disease-modifying therapies (DMTs)–and others currently under investigation–have shown promising results and significantly altered disease trajectories, the standardized in-clinic assessments commonly used as trial endpoints often fail to capture meaningful real-world mobility improvements reported by treated patients. This gap complicates accurate evaluation of therapeutic efficacy and may contribute to delays in patient access to emerging treatments. Wearable-based gait monitoring offers a practical solution for remotely assessing ambulatory function in individuals with motor impairments. Real-world gait patterns can serve as sensitive functional biomarkers to monitor treatment response and track disease progression. However, most real-world studies on NMDs have focused on volume metrics such as step count, which lack stride-level granularity and cannot capture independent gait domains, or on basic spatiotemporal (SPT) metrics related to pace, rhythm, or variability. Kinetic parameters–such as center-of-pressure (COP)-derived metrics–are critical for assessing dynamic stability and muscle strength deficits in NMDs, yet they remain largely unexplored in real-world settings. Unlike other wearables, instrumented insoles allow for the assessment of both SPT and kinetic parameters, with stride-level granularity. Towards the development of multi-domain functional digital biomarkers for ambulatory NMDs, this study evaluates the construct, concurrent, and known-groups validity of insole-based, stride-level SPT and COP-derived parameters in individuals with DMD and SMA during walking tasks designed to simulate real-world walking. Mean absolute errors (MAEs) relative to gold-standard gait-laboratory equipment were used to assess construct validity, while correlations between insole-based metrics and standardized clinical assessment tests provided proof-of-concept concurrent validity. To establish the added value of COP metrics with respect to known-groups validity, we also conducted a comparative analysis of the ability of insole-based SPT and COP-derived features to discriminate between individuals with DMD or SMA and healthy controls. Results suggest that incorporating COP-derived metrics alongside more conventional SPT measures may help better characterize disease-specific gait signatures and their relationships with functional impairment in ambulatory individuals with DMD and SMA. COP metrics were more informative than SPT measures in DMD, whereas they were largely complementary to SPT measures in SMA, with the anteroposterior range of COP (AP-COP) nonetheless standing out for its associations with lower-limb strength and walking capacity. Overall, this work provides proof-of-concept evidence of the utility of combined SPT and COP gait parameters as candidate functional digital biomarkers in ambulatory NMDs, paving the way for more extensive evaluations in free-living settings.