A5016640472- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Congenital Anomalies and Fetal Surgery
- Muscle activation and electromyography studies
- Peripheral Neuropathies and Disorders
- Hereditary Neurological Disorders
- CRISPR and Genetic Engineering
- Ion channel regulation and function
- Myasthenia Gravis and Thymoma
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Nutrition and Health in Aging
- RNA Research and Splicing
- Botulinum Toxin and Related Neurological Disorders
- Cerebral Palsy and Movement Disorders
- Amyotrophic Lateral Sclerosis Research
- Acute Myocardial Infarction Research
- Nerve injury and regeneration
- Body Composition Measurement Techniques
- Inflammatory Myopathies and Dermatomyositis
- Neuroscience and Neural Engineering
- Cardiomyopathy and Myosin Studies
- Parkinson's Disease Mechanisms and Treatments
University of Missouri
2022-2025
The Ohio State University
2015-2024
Argonne National Laboratory
2022-2024
University of Missouri System
2023-2024
The Ohio State University Wexner Medical Center
2014-2023
Ohio University
2023
University of Minnesota System
2019-2020
University of Minnesota
2020
Neurology, Inc
2020
Columbus Oncology and Hematology Associates
2014-2019
Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve milestones and death or the need for mechanical ventilation by 2 years of age. We studied functional replacement mutated gene encoding survival (SMN1) this disease.Fifteen patients SMA1 received single dose intravenous adeno-associated virus serotype 9 carrying SMN complementary DNA missing protein. Three low (6.7×1013 vg per kilogram body...
The trans hydrogen bond 3hJNC' coupling observed between peptide groups in proteins is shown to be mediated by a closed shell, noncovalent interaction the donor atom and acceptor oxygen atom. magnitude of an exponential function mutual penetration nonbonding van der Waals shells isolated fragments. Our results also show that JFF, through-space two nonbonded fluorine nuclei organic molecules protein, exhibits similar dependence upon monomer charge densities. These support idea existence...
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 Background Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic neuromuscular disease where 75% of SMA1 patients die/require permanent‐ventilation by 13.6 months. This study assessed the health outcomes infants treated with AVXS‐101 gene replacement therapy. Methods Twelve genetically confirmed homozygous deletions SMN1 and two SMN2 copies received one‐time intravenous proposed therapeutic dose in an open label conducted between December 2014 2017. Patients were followed for...
BackgroundThis study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy infants with severe spinal muscular atrophy type 1 (SMA1).MethodsThis is a follow-up analysis 12 SMA1 who received the proposed therapeutic dose Phase open-label (NCT02122952). Infants were grouped according to age at and baseline Children's Hospital Philadelphia Infant Test Neuromuscular Disorders scores: (1) dosing/low motor, dosed less than...
Spinal muscular atrophy type 1 (SMA1) is the leading genetic cause of infant mortality for which therapies, including AVXS-101 (onasemnogene abeparvovec, Zolgensma®) gene replacement therapy, are emerging.This study evaluated effectiveness in infants with spinal compared a prospective natural history cohort and healthy infants.Twelve SMA1 received proposed therapeutic dose (NCT02122952). Where possible, following outcomes were (n = 16) 27) enrolled NeuroNEXT (NN101) (NCT01736553): event-free...
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, arises from survival motor neuron (SMN) protein insufficiency resulting
Spinal muscular atrophy (SMA) is caused by reduced levels of survival motor neuron (SMN) protein, which results in motoneuron loss. Therapeutic strategies to increase SMN including drug compounds, antisense oligonucleotides, and scAAV9 gene therapy have proved effective mice. We wished determine whether reduction postnatal motoneurons resulted SMA a large animal model, could be corrected after development muscle weakness, the response clinically relevant biomarkers.Using intrathecal delivery...
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...
Limb-girdle muscular dystrophies are a genetically diverse group of diseases characterized by chronic muscle wasting and weakness. Recessive mutations in ANO5 (TMEM16E) have been directly linked to several clinical phenotypes including limb-girdle dystrophy type 2L Miyoshi myopathy 3, although the pathogenic mechanism has remained elusive. is member Anoctamin/TMEM16 superfamily that encodes both ion channels regulators membrane phospholipid scrambling. The phenotypic overlap myopathies with...
In older adults, the loss of muscle strength (dynapenia) and mass (sarcopenia) are important contributors to physical function. We sought investigate dynapenia, sarcopenia, motor unit function in aging mice. C57BL/6J mice were analyzed with cross-sectional (males: 3 vs. 27 months; males females: 8 12 20 months) longitudinal studies 10–25 using vivo electrophysiological measures connectivity (triceps surae compound action potential number estimation), plantar flexion torque, magnetic...
Abstract Recent advances in base editing have created an exciting opportunity to precisely correct disease-causing mutations. However, the large size of editors and their inherited off-target activities pose challenges for vivo editing. Moreover, requirement a protospacer adjacent motif (PAM) nearby mutation site further limits targeting feasibility. Here we modify NG-targeting adenine editor (iABE-NGA) overcome these demonstrate high efficiency edit Duchenne muscular dystrophy (DMD) adult...
Abstract Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such while impacting proteome. Here we report genome-wide analysis of mRNA methyladenosine (m 6 A) dynamics skeletal hypertrophic growth following overload-induced stress. We show that increases METTL3 (the m A enzyme), concomitantly A, control size...
Myasthenia gravis (MG) is a neuromuscular disease that results in compromised transmission of electrical signals at the junction (NMJ) from motor neurons to skeletal muscle fibers. As result, patients with MG have reduced function and present symptoms severe weakness fatigue. ClC-1 specific chloride (Cl − ) ion channel plays important roles regulating fiber excitability during intense exercise. Here, we show partial inhibition an orally bioavailable small molecule (NMD670) can restore rat...
Idiopathic peripheral neuropathy is common and likely due to genetic factors that are not detectable using standard linkage analysis. We initiated a candidate gene approach study the influence of small heat shock protein (sHSP) family on an axonal motor motor/sensory patient population.The promoter region all exonic intronic sequences 10 sHSP genes (HSPB1-HSPB10) were screened in cohort presumed nonacquired, patients seen at Ohio State University Neuromuscular Clinic.A missense mutation...
Paclitaxel is among the most widely used anticancer drugs and known to cause a dose-limiting peripheral neurotoxicity, initiating mechanisms of which remain unknown. Here, we identified murine solute carrier organic anion–transporting polypeptide B2 (OATP1B2) as mediator paclitaxel-induced neurotoxicity. Additionally, using established tests assess acute chronic found that genetic or pharmacologic knockout OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia,...