A5005113764- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Cancer-related gene regulation
- Muscle activation and electromyography studies
- Epigenetics and DNA Methylation
- Musicians’ Health and Performance
- Stroke Rehabilitation and Recovery
- Dysphagia Assessment and Management
- biodegradable polymer synthesis and properties
- Prion Diseases and Protein Misfolding
Amyotrophic Lateral Sclerosis Therapy Development Institute
2019-2024
Amyotrophic lateral sclerosis causes degeneration of motor neurons, resulting in progressive muscle weakness and impairment function. Promising drug development efforts have accelerated amyotrophic sclerosis, but are constrained by a lack objective, sensitive, accessible outcome measures. Here we investigate the use wearable sensors, worn on four limbs at home during natural behavior, to quantify function disease progression 376 individuals with sclerosis. We an analysis approach that...
Amyotrophic Lateral Sclerosis (ALS) disease severity is usually measured using the subjective, questionnaire-based revised ALS Functional Rating Scale (ALSFRS-R). Objective measures of would be powerful tools for evaluating real-world drug effectiveness, efficacy in clinical trials, and identifying participants cohort studies. We developed a machine learning (ML) based objective measure on voice samples accelerometer measurements from four-year longitudinal dataset. 584 people living with...
Digital health technologies (DHTs) can quantify movements in daily routines but rely heavily on participant adherence over prolonged wear times. Here we analyze accelerometry data from wrist-worn devices during short episodes of prescribed exercises (PEs) performed by 329 individuals living with amyotrophic lateral sclerosis (ALS) a longitudinal study. We developed an automated and interpretable signal processing method to estimate upper limb movement counts, duration, intensity, similarity...
Repeat expansion mutations in the C9ORF72 gene are most common genetic cause of amyotrophic lateral sclerosis (ALS) and (FTD). Repeat-associated non-AUG translation this produces dipeptide repeat proteins (DRPs). The arginine containing DRPs, polyGR polyPR, consistently reported to be toxic. Here we demonstrated that small molecule inhibition Type I protein methyltransferases protects against polyPR toxicity. Furthermore, our findings suggest asymmetric dimethylation by PRMTs play important...
A repeat expansion mutation in the C9orf72 gene is most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In this study, using multiple cell-based assay systems, we reveal both increased dipeptide protein (DRP) toxicity primary neurons differentiated neuronal cell lines. Using flow cytometry confocal laser scanning microscopy cells treated with fluorescein isothiocyanate (FITC)-labeled DRPs, confirm that poly-glycine-arginine (GR)...
Hexanucleotide repeat expansion (G4C2 n ) mutations in the gene C9ORF72 account for approximately 30% of familial cases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as well 7% sporadic ALS. G4C2 are known to result production five species dipeptide proteins (DRPs) through non-canonical translation processes. Arginine-enriched proteins, glycine-arginine (polyGR), proline-arginine (polyPR) have been demonstrated be cytotoxic deleterious multiple experimental systems....
Abstract ALS causes degeneration of motor neurons, resulting in progressive muscle weakness and impairment fine motor, gross bulbar, respiratory function. Promising drug development efforts have accelerated ALS, but are constrained by a lack objective, sensitive, accessible outcome measures. Here we investigate the use consumer-grade wearable sensors, worn on four limbs at home during natural behavior, to quantify function disease progression 376 individuals with over several year period. We...
Automatic prediction of amyotrophic lateral sclerosis (ALS) disease progression provides a more efficient and objective alternative than manual approaches. We propose ALS longitudinal speech transformer (ALST), neural network-based automatic predictor from recordings patients. By taking advantage high-quality pretrained features information in the recordings, our best model achieves 91.0\% AUC, improving upon previous by 5.6\% relative on TDI dataset. Careful analysis reveals that ALST is...
Automatic prediction of amyotrophic lateral sclerosis (ALS) disease progression provides a more efficient and objective alternative than manual approaches. We propose ALS longitudinal speech transformer (ALST), neural network-based automatic predictor from recordings patients. By taking advantage high-quality pretrained features information in the recordings, our best model achieves 91.0%AUC, improving upon previous by 5.6% relative on TDI dataset. Careful analysis reveals that ALST is...
Wearable technology offers objective and remote quantification of disease progression in neurological diseases such as amyotrophic lateral sclerosis (ALS). Large population studies are needed to determine generalization reproducibility findings from pilot studies. A large cohort patients with ALS (N = 202) wore wearable accelerometers on their dominant non-dominant wrists for a week every two four weeks self-entered the Functional Rating Scale-Revised (ALSFRS-RSE) similar time intervals....
ABSTRACT The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a repeat expansion mutation in the C9orf72 gene. Repeat-associated non-AUG (RAN) translation this produces five species dipeptide proteins (DRPs). arginine containing DRPs, polyGR polyPR, are consistently reported to be toxic. Here, we uncover Type I protein methyltransferase (PRMT) inhibitors as possible therapeutics for polyGR- polyPR- related toxicity. Furthermore, reveal...
ABSTRACT Amyotrophic Lateral Sclerosis (ALS) disease severity is usually measured using the subjective, questionnaire-based revised ALS Functional Rating Scale (ALSFRS-R). An objective measure for tracking and progression would be a powerful tool evaluating real-world drug effectiveness, efficacy in clinical trials, as well identifying participants cohort studies. Here we develop machine learning (ML) based severity, on voice samples accelerometer measurements from longitudinal dataset...