Multi-Modal Digital Monitoring of Disease Symptoms in Spinocerebellar Ataxia

The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of rare, autosomal dominant neurodegenerative disorders characterized by progressive degeneration of the cerebellum and its connecting pathways. The four most common subtypes (SCA1, SCA2, SCA3, and SCA6) are caused by expanded polyglutamine-coding CAG repeats, and collectively account for the majority of dominantly inherited ataxias worldwide. The cardinal feature across subtypes is progressive ataxia affecting gait, stance, limb coordination, and speech, frequently accompanied by oculomotor abnormalities and, in some subtypes, extracerebellar signs such as spasticity, peripheral neuropathy, and parkinsonism. Symptoms typically begin in adulthood and progress over many years, leading to severe disability and reduced life expectancy?life expectancy Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.. The principal means of measuring ataxia severity is the Scale for the Assessment and Rating of Ataxia (SARA), which is the most widely applied clinical outcome assessment (COA) for genetic ataxias and has been used as the primary endpoint?primary endpoint The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected. in large natural history?natural history A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials. cohorts and randomized?randomized Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable. controlled trials. Although the SARA has demonstrated good inter-rater reliability and has been validated across multiple SCA subtypes, it is inherently subjective and semi-quantitative, requires trained personnel to administer, and may not be sufficiently sensitive to detect incremental but clinically meaningful changes over short follow-up?follow-up The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes. intervals. Movement-associated symptoms are a core feature of SCA and have a substantial negative impact on quality of life. Impairments in gait and balance contribute to falls and loss of independence, while dysarthria and impaired limb coordination affect communication and activities of daily living. Because these assessments are conducted infrequently, typically in a clinic setting, they may not accurately represent an individual's true functional status during everyday life. However, the increasing understanding of disease pathomechanisms and the development of gene-targeting and other novel therapeutic approaches have raised expectations for disease-modifying treatments. The key challenge in developing new therapeutics for SCA and other neurological disorders is that current disease assessment is largely subjective and requires in-person, in-clinic evaluation. Digital measures, such as those proposed in this study, can provide objective, sensitive, and real-world assessments of how individuals are functioning. A growing body of evidence demonstrates that digital biomarkers?biomarkers Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving. derived from body-worn inertial sensors can quantify ataxia-specific gait and balance impairments, and correlate strongly with clinician-rated SARA scores. Beyond gait and balance, multi-modal digital assessment of speech, hand function, and oculomotor control may capture complementary domains of cerebellar dysfunction that are affected in SCA. Acoustic analysis of speech can quantify dysarthria, finger tapping can characterize upper-limb bradykinesia and dysrhythmia, and oculomotor testing can capture saccadic and antisaccadic abnormalities that are characteristic of cerebellar disease. Thus, a system that can objectively, sensitively, and frequently monitor multiple clinical domains (motor, speech, and oculomotor function) is necessary to understand the pattern of evolving impairment in individuals with SCA and to support the identification of endpoint?endpoint Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory. measures for therapeutic trials. This study will evaluate the feasibility of a multi-modal digital monitoring platform in a cohort?cohort A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed. of individuals with SCA and will characterize the relationship between digital measures and established clinical and patient reported outcomes.