A5029839211- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Parkinson's Disease Mechanisms and Treatments
- Peptidase Inhibition and Analysis
- Neurological disorders and treatments
- Neuropeptides and Animal Physiology
- Neurogenetic and Muscular Disorders Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Advanced Sensor and Energy Harvesting Materials
- X-ray Diffraction in Crystallography
- Respiratory Support and Mechanisms
- Diabetes Treatment and Management
- Crystallization and Solubility Studies
- Molecular spectroscopy and chirality
- Axial and Atropisomeric Chirality Synthesis
- Crystallography and molecular interactions
- DNA Repair Mechanisms
- Atrial Fibrillation Management and Outcomes
- Coenzyme Q10 studies and effects
- Prosthetics and Rehabilitation Robotics
- Muscle activation and electromyography studies
- Botulinum Toxin and Related Neurological Disorders
- Malaria Research and Control
- Computational Drug Discovery Methods
Swiss Data Science Center
2017-2025
Columbia University Irving Medical Center
2025
Johns Hopkins University
2025
University of Chicago
2025
Massachusetts General Hospital
2025
The University of Melbourne
2019-2022
Murdoch Children's Research Institute
2019-2022
Children's Hospital of Philadelphia
2021-2022
University of Pennsylvania
2021-2022
Victorian Clinical Genetics Services
2022
Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments proven efficacy. Leber’s hereditary optic neuropathy is most common disorder causing irreversible blindness young adult life. Anecdotal reports support use idebenone neuropathy, but this has not been evaluated a randomized controlled trial. We conducted 24-week multi-centre double-blind, randomized, placebo-controlled trial 85 patients...
Decline in pulmonary function Duchenne Muscular Dystrophy (DMD) contributes to significant morbidity and reduced longevity. Spirometry is a widely used fairly easily performed technique assess lung function, particular volume; however, the acceptability criteria from American Thoracic Society (ATS) may be overly restrictive inappropriate for patients with neuromuscular disease. We examined prospective spirometry data (Forced Vital Capacity [FVC] peak expiratory flow [PEF]) 60 DMD enrolled...
Background— This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia (FA) cardiomyopathy (FA-CM). Methods and Results— A comprehensive cardiac assessment, including standard echocardiography, color Doppler myocardial imaging, magnetic resonance ECG, exercise stress testing, was performed in 205 FA patients. To assess hypertrophy FA-CM, end-diastolic interventricular septal wall thickness (IVSTd) found to be best echocardiographic parameter...
The understanding of the natural history Friedreich ataxia (FRDA) has improved considerably recently, but patterns neurologic deterioration are not fully clarified, compromising assessment clinical relevance effects and guidance for study design. goal this was to acknowledge broad genetic diversity population, especially younger individuals, provide analyses stratified by age guide population selection in future studies.Based on a large study, FRDA Clinical Outcome Measures that at current...
Abstract Objective The natural history of Friedreich ataxia is being investigated in a multi‐center longitudinal study designated the Clinical Outcome Measures Study (FACOMS). To understand utility this analysis clinical trials, we performed propensity‐matched comparison data from open‐label MOXIe extension (omaveloxolone) to that FACOMS. Methods patients were matched FACOMS using logistic regression estimate propensity scores based on multiple covariates: sex, baseline age, age onset,...
Short-chain quinones have been investigated as therapeutic molecules due to their ability modulate cellular redox reactions, mitochondrial electron transfer and oxidative stress, which are pathologically altered in many neuromuscular disorders. Recently, we others described that certain short-chain able bypass a deficiency complex I by shuttling electrons directly from the cytoplasm III of respiratory chain produce ATP. Although this energy rescue activity is highly interesting for therapy...
To investigate the psychometric properties of Friedreich Ataxia Rating Scale neurologic examination (FARSn) and its subscores, as well influence modifications resulting in now widely used modified FARS (mFARS) examination.Based on cross-sectional data from FA-Clinical Outcome Measures cohort, we conducted correlation-based analyses to interplay items subscores within FARSn/mFARS constructs.The results provide support for both FARSn mFARS constructs, individually their upper limb lower...
In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe complications. Of particular concern are ineffective cough, secretion retention recurrent tract infections. a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD 10–18 years age not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the over 1-year period....
BackgroundFriedreich's ataxia (FRDA) is a characterized by progressive loss of coordination and balance leading to ambulation (LoA) in nearly all affected individuals. While transition becoming fully wheelchair bound critical milestone the disease course, it presents particularly challenging prediction, mostly due variability inter- intra-subject severity progression. For these reasons, LoA or potential surrogates have been impractical as outcomes clinical trials.MethodsWe studied features...
The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). also characterized therapeutic potential idebenone protecting patients from developing dyschromatopsia LHON.Color contrast data 39 LHON participating a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported onset <5 years before enrolment genetically confirmed. Protan sensitivity was measured using...
Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study 10–18 year old DMD the assessment inter-correlation between tests (PFTs), their reliability association general disease stage measured by Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], volume one second [FEV1]) maximum static airway pressures (MIP, MEP) were prospectively collected from 64 enrolled...
Patients with symptomatic internal carotid artery (ICA) stenosis are at high risk of recurrent ischemic stroke and require early interventional treatment antiplatelet therapy. Increased bleeding rates might counterbalance the periprocedural efficacy intensified platelet inhibition. We aim to investigate, whether Revacept, a competitive antagonist glycoprotein VI, adjunct standard therapy reduces occurrence lesions in patients ICA stenosis.International, multicenter (16 sites), 3-arm,...
Abstract Objective Most individuals with Friedreich ataxia (FRDA) have homozygous GAA triplet repeat expansions in the FXN gene, correlating a typical phenotype of and cardiomyopathy. A minority are compound heterozygotes carrying expansion on one allele mutation other. The study aim was to examine phenotypic variation among heterozygotes. Methods Data mutations were obtained from Ataxia Clinical Outcome Measures Study (FA‐COMS). We compared clinical features single‐site FA‐COMS cohort 51...
Simple peroxomolybdenum Mimoun complexes become catalytically active in phase-transfer epoxidations with hydrogen peroxide, if the oxenoid is extracted from water into organic phase by surfactant-type ligands OER3 (E = N, P, As; R long-chain alkyl; see scheme). Mechanistic studies, Raman spectroscopy, and denisty functional calculations are combined an investigation of species.
Abstract Dipeptidyl peptidase 4 (DP4) inhibitors are currently under intensive investigation in late‐stage clinical trials as a treatment for type II diabetes. Lack of selectivity toward the related enzymes DP8 and DP9 has recently emerged possible source drug‐induced toxicity. Unlike DP4, X‐ray structures not yet available. As an aid to understanding structural basis selectivity, authors have constructed homology models based on coordinates DP4. Accurate sequence alignment reveals common...
The aim of this cross-sectional study was to analyse disease progression in Friedreich's ataxia as measured by the International Cooperative Ataxia Rating Scale. Single ratings from 603 patients with were analysed a function duration, age onset and GAA repeat lengths. relative contribution items subscales total score studied progression. In addition, scaling properties assessed using standard statistical measures. Average scale per year depends on onset, time since diagnosis length....
Summary Assessment of dynamic inspiratory function may provide valuable information about the degree and progression pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims this study were to characterize assess efficacy idebenone on outcome a large well‐characterized cohort 10–18 year‐old DMD not taking glucocorticoid steroids (GCs) enrolled phase 3 randomized controlled DELOS trial. We evaluated effect highest flow generated during an FVC maneuver (maximum flow;...
3D QSAR models based on the CoMSIA descriptor fields were established using a diverse data set of 53 antimalarial biaryl compounds (tested in vitro against chloroquine-resistant strain Plasmodium falciparum), consisting mainly naphthylisoquinoline alkaloids, but also including phenylanthraquinone structures and naphthylindenes. For alignment, two commercially available automated approaches, FLEXS GASP, compared; initially none them succeeded treating important phenomenon axial chirality...
Gait assessments in a clinical setting may not accurately reflect mobility everyday life. To better understand gait during daily life, we compared measures that discriminated Friedreich ataxia (FRDA) from healthy control (HC) subjects prescribed clinic tests and free, daily-life monitoring. We recruited 9 people with FRDA (median age: 20, IQR [12, 48] years). A comparative subject cohort of was sampled using propensity matching on age 18 [13, 22] Subjects wore 3 inertial sensors (one each...