Consumer-grade wearables and machine learning sensitively capture disease progression in amyotrophic lateral sclerosis

ALS causes degeneration of motor neurons, resulting in progressive muscle weakness and impairment in fine motor, gross motor, bulbar, and respiratory function. Promising drug development efforts have accelerated in ALS, but are constrained by a lack of objective, sensitive, and accessible outcome measures. Here we investigate the use of consumer-grade wearable sensors, worn on four limbs at home during natural behavior, to quantify motor function and disease progression in 376 individuals with ALS over a several year period. We utilized an analysis approach that automatically detects and characterizes submovements from passively collected accelerometer data and produces a machine-learned severity score for each limb that is independent of clinical ratings. The approach produced interpretable and highly reliable scores that progressed faster than the gold standard ALS Functional Rating Scale-Revised (−0.70 SD/year versus -0.48 SD/year), supporting its use as a sensitive, ecologically valid, and scalable measure for ALS trials and clinical care. ### Competing Interest Statement For the methods for analyzing wearable sensor data, a PCT (US2022/081374) was filed on December 12, 2022, titled: System and method for clinical disorder assessment. An earlier US Provisional Application (Serial No. 63/288,619) was filed on December 12, 2021. ### Funding Statement This work was funded in part by NIH R01 NS117826. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This research study was conducted in accordance with the ethical principles posited in the Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Protocol approval was provided by the institutional review board (ADVARRA CIRBI). Every participant consented to participate in this research by signing an IRB approved informed consent form. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data included in this study will be shared by request from any qualified investigator.