A5033266587- Muscle Physiology and Disorders
- Neurogenetic and Muscular Disorders Research
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Muscle activation and electromyography studies
- Vitamin D Research Studies
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Nutrition and Health in Aging
- Children's Physical and Motor Development
- RNA modifications and cancer
- Nuclear Structure and Function
- Exercise and Physiological Responses
- Cerebral Palsy and Movement Disorders
- Prosthetics and Rehabilitation Robotics
- Tissue Engineering and Regenerative Medicine
- Muscle metabolism and nutrition
- Congenital Anomalies and Fetal Surgery
- Cardiovascular Effects of Exercise
- Coenzyme Q10 studies and effects
- Metabolism and Genetic Disorders
- Neonatal Respiratory Health Research
- Growth Hormone and Insulin-like Growth Factors
- Adrenal Hormones and Disorders
University of Massachusetts Chan Medical School
2018-2024
UCLA Health
2024
University of Colorado Anschutz Medical Campus
2024
University of California, Los Angeles
2022-2024
Analysis Group (United States)
2023
University College London
2023
UMass Memorial Medical Center
2019-2023
Yale New Haven Hospital
2023
Memorial Medical Center
2020-2023
Great Ormond Street Hospital
2023
Spinal muscular atrophy is a neurodegenerative disease that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis spinal and advances technology have not been matched by similar developments care for patients. Variations practice coupled with differences family resources values resulted variable clinical outcomes are likely to compromise valid measure treatment effects during trials. The International Standard Care Committee Muscular Atrophy...
Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough premature stop codons mutation (nm) genetic disorders.
Mutations in the DMD gene, encoding dystrophin protein, are responsible for dystrophinopathies Duchenne Muscular Dystrophy (DMD), Becker (BMD), and X-linked Dilated Cardiomyopathy (XLDC). Mutation analysis has traditionally been challenging, due to large gene size (79 exons over 2.2 Mb of genomic DNA). We report a very aggregate data set comprised mutations detected samples from patients enrolled United Dystrophinopathy Project, multicenter research consortium, referral submitted mutation...
Background Approximately 13% of boys with Duchenne muscular dystrophy (DMD) have a nonsense mutation in the dystrophin gene, resulting premature stop codon corresponding mRNA and failure to generate functional protein. Ataluren (PTC124) enables ribosomal readthrough codons, leading production full-length, proteins. Methods This Phase 2a open-label, sequential dose-ranging trial recruited 38 DMD. The first cohort (n = 6) received ataluren three times per day at morning, midday, evening doses...
We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) recombinant adeno-associated virus (rAAV) serotype 9 containing d
Purpose To analyze T2 maps of pelvic and thigh muscles in Duchenne muscular dystrophy (DMD), to identify the most severely affected muscle, correlate muscle with grade fatty infiltration at nonquantitative magnetic resonance (MR) imaging results clinical assessment. Materials Methods This prospective study was HIPAA compliant approved by institutional review board; written consent obtained from all participants' parents or guardians. Thirty-four boys DMD (mean age, 8.4 years) were evaluated...
Children with limited or no ability to ambulate frequently sustain fragility fractures. Joint contractures, scoliosis, hip dysplasia, and metallic implants often prevent reliable measures of bone mineral density (BMD) in the proximal femur lumbar spine, where BMD is commonly measured. Further, relevance spine fracture risk this population questionable. In an effort obtain that are both technically feasible clinically relevant, a technique was developed involving dual-energy X-ray...
Background Patients with Duchenne muscular dystrophy exhibit progressive cardiac and skeletal muscle dysfunction. Based on prior data, dysfunction in patients may be influenced by myocardial fibrosis steroid therapy. We examined the longitudinal relationship of ventricular using magnetic resonance a large cohort. Methods Results reviewed 465 serial studies (98 ≥4 studies) for left ejection fraction ( LVEF ) presence late gadolinium enhancement LGE ), marker fibrosis. was modeled examining...
The purpose of this study was to assess health-related quality life (QoL) in children with Duchenne muscular dystrophy (DMD), including development and field-testing a DMD-specific module integrated the core Pediatric Quality Life Inventory (PedsQL).The PedsQL 4.0 Generic Core DMD Module Scales were completed by 203 families, 200 parents 117 boys DMD. Scores on compared those matched healthy children. Relationships between scores patient characteristics examined.By both parent report child...
An N-of-1 trial was developed to deliver a dCas9-VP64 transgene designed upregulate the cortical dystrophin as custom therapy for Duchenne muscular dystrophy (DMD) patient. After showing signs of mild cardiac dysfunction and pericardial effusion, patient acutely decompensated sustained arrest six-days after dosing succumbed two-days later. Post-mortem examination revealed severe acute-respiratory distress syndrome with diffuse alveolar damage. Vector biodistribution data obtained minimal...
Abstract Recent reports highlight the utility of in vivo magnetic resonance spectroscopy (MRS) techniques to recognize creatine deficiency syndromes affecting central nervous system (CNS). Reported cases demonstrate partial reversibility neurologic symptoms upon restoration CNS levels with administration oral creatine. We describe a patient brain syndrome detected by proton MRS that differs from published reports. Metabolic screening revealed elevated serum and urine, normal guanidino acetic...
Nonsense mutations are usually predicted to function as null alleles due premature termination of protein translation. However, nonsense in the DMD gene, encoding dystrophin protein, have been associated with both severe Duchenne Muscular Dystrophy (DMD) and milder Becker (BMD) phenotypes. In a large survey, we identified 243 unique for 210 these could establish definitive We analyzed reading frame by exons flanking those which were found, present evidence that resulting BMD likely do so...
<h3>Background:</h3> Infantile cardiomyopathy is a genetically heterogeneous disorder with significant morbidity and mortality. <h3>Methods:</h3> This study aimed to identify the mutation present in four unrelated patients who presented as infants isolated hypertrophic cardiomyopathy. <h3>Results:</h3> In all four, novel mitochondrial m.8528T→C was identified. results change of initiation codon ATPase 6 threonine concurrent from highly conserved hydrophobic amino acid, tryptophan, at...
To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens decline in ambulatory ability boys with Duchenne muscular dystrophy (DMD).Three hundred thirty-one participants DMD 7 14 years of age taking glucocorticoids were tadalafil 0.3 mg·kg-1·d-1, 0.6 or placebo. The efficacy measure was 6-minute walk distance (6MWD) after weeks. Secondary measures included North Star Ambulatory Assessment and timed function tests....
We studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchenne muscular dystrophy by assessing additive predictive value vastus lateralis (VL) fat fraction (FF) to age on loss ambulation (LoA).VL FFs were determined longitudinal Dixon scans from 2 natural history studies Leiden University Medical Center (LUMC) and Cincinnati Children's Hospital (CCHMC). CCHMC included ambulant patients, while LUMC mixed nonambulant population. fitted VL FF values sigmoidal curve...