A5103271570- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Muscle Physiology and Disorders
- Congenital Anomalies and Fetal Surgery
- Genetics and Neurodevelopmental Disorders
- Cardiomyopathy and Myosin Studies
- Congenital Diaphragmatic Hernia Studies
- Muscle activation and electromyography studies
- Long-Term Effects of COVID-19
- Adipose Tissue and Metabolism
- Advanced Sensor and Energy Harvesting Materials
- Congenital heart defects research
- Neonatal Respiratory Health Research
- Energy Harvesting in Wireless Networks
- CRISPR and Genetic Engineering
- Family and Disability Support Research
- Genetic Neurodegenerative Diseases
- Infectious Encephalopathies and Encephalitis
- COVID-19 Clinical Research Studies
- Myasthenia Gravis and Thymoma
- RNA Research and Splicing
- Mechanical Circulatory Support Devices
- Kawasaki Disease and Coronary Complications
- Protease and Inhibitor Mechanisms
- Genomic variations and chromosomal abnormalities
University of Colorado Denver
2015-2024
Children's Hospital Colorado
2010-2024
University of Colorado Anschutz Medical Campus
2019-2020
University of Colorado Health
2005-2007
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...
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%)...
Abstract Introduction/Aims NURTURE (NCT02386553) is an open‐label study of nusinersen in children (two SMN2 copies, n = 15; three 10) who initiated treatment the presymptomatic stage spinal muscular atrophy (SMA). A prior analysis after ~3 y showed benefits on survival, respiratory outcomes, motor milestone achievement, and a favorable safety profile. An additional 2 follow‐up (data cut: February 15, 2021) are reported. Methods The primary endpoint time to death or intervention (≥6 h/day...
This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).This prospective, multi-center natural history targeted the enrollment of SMA and healthy control less than 6 months age. Recruitment occurred at 14 centers within NINDS National Network Excellence Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales electrophysiological, protein molecular were baseline subsequent visits.Enrollment began...
Abstract Polymicrogyria is a malformation of cortical development characterized by loss the normal gyral pattern, which replaced many small and infolded gyri separated shallow, partly fused sulci, middle layers. The pathogenesis unknown, yet emerging data supports existence several loci in human genome. We report on clinical brain imaging features, results cytogenetic molecular genetic studies 29 patients with polymicrogyria associated structural chromosome rearrangements. Our map new...
Electrical impedance myography (EIM) is a non-invasive, painless, objective technique to quantify muscle pathology.We measured EIM in 8 arm and leg muscles 61 boys with Duchenne muscular dystrophy (DMD) 31 healthy boys, ages 3-12 years, at 5 centers. We determined the reliability of compared results DMD controls 6-minute walk distance (6MWD), North Star Ambulatory Assessment (NSAA), timed functional tests (TFTs), strength (hand-held dynamometry).EIM was well tolerated had good inter-...
To analyze the spectrum of neurological manifestations in children hospitalized with pandemic influenza A H1N1 virus 2009 (pH1N1).Retrospective case series from May 1, 2009, through November 30, 2009.Tertiary-care children's hospital Colorado.All patients pH1N1 consult or diagnosis, lumbar puncture, electroencephalogram, neuroimaging were selected as suspected cases. These systematically reviewed and for final analysis if confirmed by pre-established definitions a complication.Of 307 pH1N1,...
Summary Introduction Spinal muscular atrophy is characterized by loss of motor neurons in the anterior horn spinal cord with resultant proximal muscle weakness. Intrathecal nusinersen has revolutionized treatment atrophy. We reviewed perioperative care 61 anesthetics performed on eight patients type 2 who received over 30 months conjunction nusinersen's phase 3 clinical trials. Methods Anesthesia was induced all sevoflurane, nitrous oxide, and oxygen (30%) via facemask. A peripheral...
Abstract Celiac disease has been associated with ataxia and other neurological signs but not paroxysmal nonkinesigenic dyskinesias (PNKD) to date. We present a child biopsy‐proven celiac movement disorder resembling PNKD since the age of 6 months. She had complete resolution her symptoms introduction gluten‐free diet. Because susceptibility locus for reported on 2q33 studies in show linkage 2q, this report suggests further genetic investigations around may be useful. also review literature...
Recruitment and retention of research participants are challenging critical components successful clinical trials natural history studies. Infants with spinal muscular atrophy (SMA) have been a particularly population to study due their fragile complex medical issues, poor prognosis and, until 2016, lack effective therapies. healthy infants into studies is also sometimes assumed not be feasible.In 2011, our group initiated two-year, longitudinal SMA infant controls provide data assist in the...
In the United States and around world, newborns are screened on a population basis for conditions benefiting from pre-symptomatic diagnosis treatment. The number of continues to expand as novel technologies screening, diagnosing, treating, managing disease discovered. While screening all facilitates early treatment, most treatable but not curable. Patients identified by newborn often require lifelong medical management community support achieve best possible outcome. To advance long-term...
Duchenne muscular dystrophy (DMD) is a rare, X-linked, progressive, degenerative muscle disease due to pathogenic variants in the DMD gene resulting absence of functional dystrophin protein.1 Patients with have irreversible damage that begins at birth, and there histologic evidence progression progressive inflammation fibrosis within first years life.2 Proactive interdisciplinary care, corticosteroids, advances disease-modifying treatments changed trajectory disease, leading slower improving...
Abstract Introduction/Aims While prompt identification and treatment of infants with spinal muscular atrophy (SMA) can ameliorate outcomes, variability persists. This study assessed management outcomes early‐treated SMA. Methods We analyzed retrospective data at 12 centers on SMA treated age ≤6 weeks from August 2018 to December 2023. Results Sixty‐six patients, 35 two SMN2 copies 31 ≥3 copies, were included. Twenty‐five (38%, 22 copies), had findings before initial which was onasemnogene...
This study evaluates safety and efficacy of onasemnogene abeparvovec-xioi (formerly AVXS-101), a survival motor neuron gene (SMN)–replacement therapy, in presymptomatic SMA patients.