Content Validity of the Spinocerebellar Ataxia Composite Score as a Measure of Disease Progression in Patients with Spinocerebellar Ataxia.

Spinocerebellar ataxia (SCA) composite score (SCACOMS) is a statistically-derived composite measure comprising weighted items that are sensitive to change during early-stage disease. SCACOMS items and weights include the functional Scale for the Assessment and Rating of Ataxia Gait (12%), Stance (17%), Sitting (8%), and Speech (10%) items, and the Clinician Global Impression of Change (CGI) (53%). The content validity of SCACOMS is yet to be established.

Best Oculomotor Endpoints for Clinical Trials in Hereditary Ataxias: A Systematic Review and Consensus by the Ataxia Global Initiative Working Group on Digital‑Motor Biomarkers.

Oculomotor deficits are common in hereditary cerebellar ataxias (HCAs) and their quantitative assessment offers a sensitive and reliable manner to capture disease-severity and progression. As a group of experts of the Ataxia Global Initiative to support trial readiness, we previously established harmonized methodology for quantitative oculomotor assessments in HCAs. Here, we aimed to identify to most promising oculomotor/vestibular outcomes as endpoints for future trials.

Disease Progression in Children With Friedreich Ataxia: Functional Performance and Other Outcome Assessments in the FACHILD Study.

BackgroundFriedreich ataxia is a rare genetic disorder caused by mutations in the gene, typically presenting with balance and coordination difficulties between ages 7 and 15 years. Neurologic symptoms are progressive and lead to loss of ambulation and especially in children other symptoms such as cardiomyopathy, scoliosis, and fatigue are common. The FACHILD natural history study aimed to expand knowledge about the disease course and evaluate clinical outcome assessments in children.

Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease.

BackgroundThe Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a novel patient-reported outcome (PRO) scale developed to assess the impact of cognitive impairment on daily functioning in early HD patients.ObjectiveTo examine the psychometric properties, including reliability and validity, of the Hi-DEF. Findings from psychometric analyses using classical test theory (CTT) approach are presented here.

The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA).

Hereditary ataxias are progressive neurodegenerative disorders primarily affecting the cerebellum. Since 2009, the Clinical Research Consortium for the Study of Cerebellar Ataxias (CRC-SCA) has studied the natural history of common types of spinocerebellar ataxias (SCAs). The CRC-SCA is a 17-site academic collaboration supported by the National Ataxia Foundation.

The clinical burden of Friedreich ataxia in the United States: A retrospective claims database analysis.

Background: Friedreich ataxia (FRDA) is a terminal, rare, autosomal recessive genetic disorder associated with debilitating comorbidities. However, limited real-world data on clinical outcomes associated with FRDA have been presented.

Methods: The Komodo Research Data (01/2016-03/2023) was used to identify patients with FRDA who had ≥2 independent non-diagnostic early-onset cerebellar ataxia codes, 1 non-diagnostic FRDA specific code, and ≥12 months of continuous enrollment before and after the index date (defined as a random date with FRDA diagnosis).

Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations.

Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years and is under clinical development for pediatric patients. In the MOXIe study, alanine and aspartate aminotransferase (ALT and AST) elevations were among the most common treatment-emergent adverse events (TEAEs) in the omaveloxolone arm and were mild to moderate, generally asymptomatic, transient, and reversible; no patients who received omaveloxolone had laboratory abnormalities that met the Hy's law criteria. Omaveloxolone labels (US and EU) provide guidance for monitoring and managing these elevations.

Spinocerebellar Ataxia Progression Measured with the Patient-Reported Outcome Measure of Ataxia.

Background: The Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) has been validated cross-sectionally but not longitudinally.

Objective: We aimed to validate PROM-Ataxia as a measure of patient experience of disease over time, examine overall and domain-specific progression, and test convergent validity with other clinical outcome assessments (COAs).

Methods: We derived PROM-Ataxia data from 176 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, or 10 in the Clinical Research Consortium for the Study of Cerebellar Ataxia at baseline and 1 year.

A global perspective on research advances and future challenges in Friedreich ataxia.

Friedreich ataxia (FRDA) is a rare multisystem, life-limiting disease and is the most common early-onset inherited ataxia in populations of European, Arab and Indian descent. In recent years, substantial progress has been made in dissecting the pathogenesis and natural history of FRDA, and several clinical trials have been initiated. A particularly notable recent achievement was the approval of the nuclear factor erythroid 2-related factor 2 activator omaveloxolone as the first disease-specific therapy for FRDA.

Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia.

Background: Dexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes (EryDex) was developed as an alternative to standard glucocorticoids in an effort to eliminate chronic steroid toxicity while preserving efficacy. The primary objective of this report is to describe the safety of long-term use of EryDex in treatment of pediatric patients with ataxia telangiectasia.

Methods: This is a post-hoc analysis of patients treated with EryDex for a minimum of 24 months in two prospective clinical trials.

Longitudinal Changes in Patient- and Clinical-Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the IDEA Study.

Background: Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients.

Objectives: To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6.

Methods: We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls.

Racial Disparities in Time to Huntington Disease Diagnosis in North America: An ENROLL-HD Analysis.

Background And Objectives: There are well-documented racial and ethnic disparities in access to neurologic care and disease-specific outcomes. Although contemporary clinical and neurogenetic understanding of Huntington disease (HD) is thanks to a decades-long study of a Venezuelan cohort, there are a limited number of studies that have evaluated racial and ethnic disparities in HD. The goal of this study was to evaluate disparities in time from symptom onset to time of diagnosis of HD.

Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.

Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B).

Objectives: Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.

Methods: We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States.

Constructing the "Family Personality": Can Family Functioning Be Linked to Parent-Child Interpersonal Neural Synchronization?

Introduction: Early child development occurs within an interactive environment, initially dominated by parents or caregivers, and is heavily influenced by the dynamics of this social context. The current study probed the neurobiology of "family personality", or family functioning, in the context of parent-child dyadic interaction using a two-person neuroimaging modality.

Methods: One hundred and five parent-child dyads (child mean age 5 years 4 months) were recruited.

Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

Background: Ataxia telangiectasia is a multisystem disorder with progressive neurodegeneration. Corticosteroids can improve neurological functioning in patients with the disorder but adrenal suppression and symptom recurrence on treatment discontinuation has limited their use, prompting the development of novel steroid delivery systems. The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in children with ataxia telangiectasia.

Long non-coding RNA is downregulated in Friedreich's ataxia.

Friedreich's ataxia is a neurodegenerative disorder caused by reduced frataxin levels. It leads to motor and sensory impairments and has a median life expectancy of around 35 years. As the most common inherited form of ataxia, Friedreich's ataxia lacks reliable, non-invasive biomarkers, prolonging and inflating the cost of clinical trials.

CRPD frontiers in movement disorders Therapeutics: From evidence to treatment and applications: Addressing Patients' Needs in the Management of the Ataxias.

The genetic ataxias have no cures and no proven ways to delay progression (no disease-modifying therapies). The acquired ataxias may have treatments that address the underlying cause and may slow or stop progression, but will not reverse damage already sustained. The idiopathic ataxias (of unknown genetic or acquired cause) also have no proven disease-modifying therapies.

Content Validity of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Instrument in Spinocerebellar Ataxia.

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA.

Development and Validation of SCACOMS, a Composite Scale for Assessing Disease Progression and Treatment Effects in Spinocerebellar Ataxia.

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763).