The Digital Frontier in Huntington's Disease: Opportunities for Clinical Trials.

The emergence of genetic and disease-modifying interventions in Huntington's disease (HD) necessitates early and accurate assessment of disease progression. Current end points, such as the Unified Huntington's Disease Rating Scale's Total Functional Capacity Scale and Total Motor Score, are insufficiently sensitive to detect subtle changes in early HD. Digital measures offer a promising solution by providing objective and sensitive assessments of a spectrum of impairments in early HD. Despite their potential, formal validation studies are lacking. The HD Integrated Staging System aims to standardize clinical research, but digital measures have yet to be evaluated within this framework. This review examines the current state of digital measures in HD and proposes a roadmap for future research. Current studies in neurodegenerative diseases and specifically in HD show promise for digital measures in early-stage clinical trials, but more research is needed to assess longitudinal performance and sensitivity to disease progression. Digital health technologies, including portable and wearable devices, can provide continuous data reflecting real-life performance. Measurements derived from these devices have the potential to serve monitoring and response biomarker roles in HD clinical research, aiding early decision-making in trials. This review underscores the need for validation and regulatory considerations for digital measures as clinical trial end points and also the importance of understanding the relationship between digital measures and meaningful aspects of health, particularly before clinical motor diagnosis. Future research should focus on establishing digital measures as sensitive and clinically meaningful end points for early HD, integrating them with patient-reported outcomes to inform therapeutic development. © 2025 International Parkinson and Movement Disorder Society.