A5047421271- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Congenital Anomalies and Fetal Surgery
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Myasthenia Gravis and Thymoma
- Mitochondrial Function and Pathology
- Family and Disability Support Research
- Nuclear Structure and Function
- Pharmacological Effects and Toxicity Studies
- Ion channel regulation and function
- Drug Transport and Resistance Mechanisms
- Cellular transport and secretion
- Prosthetics and Rehabilitation Robotics
- Mechanical Circulatory Support Devices
- Inflammatory Myopathies and Dermatomyositis
- Microtubule and mitosis dynamics
- Muscle metabolism and nutrition
- RNA Research and Splicing
- Hereditary Neurological Disorders
- Genomics and Rare Diseases
- Dermatological diseases and infestations
- Cerebral Palsy and Movement Disorders
The University of Texas Southwestern Medical Center
2016-2025
Southwestern Medical Center
2013-2024
Children's Medical Center
2008-2021
Boston Children's Hospital
2013-2019
Columbia University
2005-2019
Massachusetts General Hospital
2019
Ionis Pharmaceuticals (United States)
2016-2019
Barrow Neurological Institute
2019
Scientific Solutions (United States)
2019
Infinity Vision Dallas
2019
Nusinersen is an antisense oligonucleotide drug that modulates pre–messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for treatment spinal muscular atrophy (SMA).
This is the second half of a two-part document updating standard care recommendations for spinal muscular atrophy published in 2007. part includes updated on pulmonary management and acute issues, topics that have emerged last few years such as other organ involvement severe forms role medications. Ethical issues choice palliative versus supportive are also addressed. These becoming increasingly relevant given recent clinical trials prospect commercially available therapies will likely...
<h3>Objective:</h3> To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMN<sub>Rx</sub>), an antisense oligonucleotide designed to alter splicing <i>SMN2</i> mRNA, in patients with childhood spinal muscular atrophy (SMA). <h3>Methods:</h3> Nusinersen was delivered by injection medically stable type 2 3 SMA aged 2–14 years open-label phase 1 study its long-term extension. Four ascending single-dose levels (1, 3, 6, 9...
Duchenne muscular dystrophy (DMD) is a fatal disease caused by mutation of the gene encoding cytoskeletal protein dystrophin. Despite wealth recent information about molecular basis DMD, effective treatment for this does not exist because mechanism which dystrophin deficiency produces clinical phenotype unknown. In both mouse and human skeletal muscle, results in loss neuronal nitric oxide synthase, normally localized to sarcolemma as part dystrophin–glycoprotein complex. Recent studies mice...
Objective Infantile‐onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death preceding age 2. Clinical trials this population require an understanding disease progression and identification meaningful biomarkers to hasten therapeutic development predict outcomes. Methods A longitudinal, multicenter, prospective natural history study enrolled 26 SMA infants 27 control aged <6 months. Recruitment occurred at 14 centers over 21...
<h3>Objective</h3> To report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA). <h3>Methods</h3> Analyses included from a phase 1b/2a study (ISIS-396443-CS2; NCT01703988) who first received during that and were eligible to continue treatment the extension (ISIS-396443-CS12; NCT02052791). The was 253-day, ascending dose (3, 6, 9, 12 mg), multiple-dose, open-label, multicenter enrolled SMA aged 2–15 years. 715-day, single-dose level (12 mg) study....
Abstract SPR1NT ( NCT03505099 ) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks life. Here, we report final results 14 two copies SMN2 , expected develop spinal muscular atrophy (SMA) type 1. Efficacy compared matched Pediatric Neuromuscular Clinical Research natural-history cohort n = 23). All enrolled infants sat independently ≥30 seconds any visit...
Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT ( NCT03505099 ), a Phase III, multicenter, single-arm trial, investigated the efficacy safety of onasemnogene abeparvovec for presymptomatic mutations treated within six postnatal weeks. Of 15 before symptom onset, all stood independently 24 months (P < 0.0001; 14 normal developmental window), walked 11 window). All survived without permanent ventilation at months; ten (67%)...
Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene micro-dystrophin, engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It approved the US and other select countries. Two serious adverse event cases immune-mediated myositis (IMM) were reported phase Ib ENDEAVOR trial (NCT04626674). We hypothesized immune responses micro-dystrophin product may have mediated these IMM...
Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate contrast to its greater solubility brain. Immunohistochemistry shows nNOS localized the sarcolemma, with enrichment at force transmitting sites, myotendinous junctions, and costameres. Because this distribution similar dystrophin, we determined if expression was affected by loss of dystrophin. Significant immunoreactivity enzyme activity absent tissues from patients Duchenne muscular...
Abstract A previous study of 4 patients defined Andersen's syndrome (AS) as a triad potassium‐sensitive periodic paralysis, ventricular dysrhythmias, and dysmorphic features. AS appears to be distinct in terms its genetic defect from the α‐subunit skeletal muscle sodium channel cardiac potassium responsible for most long QT syndromes (LQT1). We studied 11 additional with 5 kindreds. Spontaneous attacks paralysis were associated hypokalemia, normokalemia, or hyperkalemia. All had similar The...
Congenital muscular dystrophies are a group of rare neuromuscular disorders with wide spectrum clinical phenotypes. Recent advances in understanding the molecular pathogenesis congenital dystrophy have enabled better diagnosis. However, medical care for patients remains very diverse. Advances many areas technology not been adopted practice. The International Standard Care Committee Muscular Dystrophy was established to identify current issues, review literature evidence-based practice, and...
To identify causative genes for centronuclear myopathies (CNM), a heterogeneous group of rare inherited muscle disorders that often present in infancy or early life with weakness and hypotonia, using next-generation sequencing whole exomes genomes. Whole-exome -genome was performed cohort 29 unrelated patients clinicopathologic diagnoses CNM related myopathy depleted cases mutations MTM1, DNM2, BIN1. Immunofluorescence analyses on biopsies, splicing assays, gel electrophoresis patient...
We studied serum vitamin E levels and the ratio of to lipid in 11 children with chronic cholestasis complicated by deficiency, as defined characteristic neurologic signs or sural-nerve histopathology addition impaired intestinal absorption E. Eight had low E, well ratios total lipids cholesterol. However, three patients normal but (two cholesterol). In four who were not E-deficient, all values normal. conclude that deficiency may exist a child concentration is most reliable biochemical index...