A5025781296- Muscle Physiology and Disorders
- Peripheral Neuropathies and Disorders
- Myasthenia Gravis and Thymoma
- Neurogenetic and Muscular Disorders Research
- Inflammatory Myopathies and Dermatomyositis
- Hereditary Neurological Disorders
- Amyotrophic Lateral Sclerosis Research
- Genetic Neurodegenerative Diseases
- Lysosomal Storage Disorders Research
- Ion channel regulation and function
- Glycogen Storage Diseases and Myoclonus
- Autoimmune Neurological Disorders and Treatments
- Cardiomyopathy and Myosin Studies
- Botulinum Toxin and Related Neurological Disorders
- Peripheral Nerve Disorders
- Parkinson's Disease and Spinal Disorders
- Nutrition and Health in Aging
- Nerve injury and regeneration
- Nuclear Structure and Function
- Muscle activation and electromyography studies
- Eosinophilic Disorders and Syndromes
- Children's Physical and Motor Development
- Biochemical and Molecular Research
- Neurological diseases and metabolism
- Pain Mechanisms and Treatments
Washington University in St. Louis
2016-2025
Ludwig-Maximilians-Universität München
2024
Friedrich Baur Stiftung
2024
University of Rochester Medical Center
2016-2022
Hackensack University Medical Center
2022
Carolinas Healthcare System
2022
Neurosciences Institute
2022
Columbia University Irving Medical Center
2022
University of Kansas Medical Center
2016-2021
University of Utah
2009-2021
Pompe's disease is a metabolic myopathy caused by deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset characterized progressive muscle weakness and loss respiratory function, leading to early death. We conducted randomized, placebo-controlled trial alglucosidase alfa, recombinant human GAA, for the treatment late-onset disease.Ninety patients who were 8 years age or older, ambulatory, free invasive ventilation randomly assigned receive biweekly...
Abstract Recently, the excitatory amino acid neurotransmitter glutamate was implicated in pathogenesis of a variety chronic degenerative neurological diseases humans and animals. This report describes abnormalities acids central nervous system 18 patients with amyotrophic lateral sclerosis (ALS). The concentration aspartate cerebrospinal fluid were increased significantly ( p > 0.01) by 100 to 200% ALS. Similarly, concentrations neuropeptide N‐acetyl‐aspartyl its metabolite,...
We report 2 patients with a treatable, immune-mediated motor polyneuropathy associated antibodies to defined neural antigens. In these asymmetrical weakness developed in one arm and progressed over 3 years involve the other arm, legs, trunk. Both were initially diagnosed as having lower neuron forms of amyotrophic lateral sclerosis. However, repeated electrophysiological testing eventually showed multifocal conduction blocks but not sensory fibers compatible patchy selective demyelination....
Abstract To identify novel causes of familial neurodegenerative diseases, we extended our previous studies TAR DNA‐binding protein 43 (TDP‐43) proteinopathies to investigate TDP‐43 as a candidate gene in cases motor neuron disease. Sequencing the led identification missense mutation, Ala‐315‐Thr, which segregates with all affected members an autosomal dominant disease family. The mutation was not found 1,505 healthy control subjects. discovery family dominantly inherited provides evidence...
Mutations in SOD1 cause 13% of familial amyotrophic lateral sclerosis. In the Gly93Ala rat model sclerosis, antisense oligonucleotide ISIS 333611 delivered to CSF decreased mRNA and protein concentrations spinal cord tissue prolonged survival. We aimed assess safety, tolerability, pharmacokinetics after intrathecal administration patients with SOD1-related sclerosis.In this randomised, placebo-controlled, phase 1 trial, we by infusion using an external pump over 11·5 h at increasing doses...
Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration tofersen being studied for treatment amyotrophic lateral sclerosis (ALS) due mutations.We conducted a phase 1-2 ascending-dose trial evaluating in adults with ALS mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned 3:1 ratio receive five doses placebo, administered...
Mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) are most commonly identified cause of Charcot-Marie-Tooth type (CMT2), a dominantly inherited disease characterized by degeneration peripheral sensory and motor axons. However, mechanism which mutations this ubiquitously expressed lead to neuropathy has not yet been elucidated. To explore how MFN2 axons, we neuropathy-associated forms cultured dorsal root ganglion neurons, cells preferentially affected CMT2. Disease-associated...
Myostatin is an endogenous negative regulator of muscle growth and a novel target for diseases. We conducted safety trial neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker dystrophy, facioscapulohumeral limb-girdle dystrophy).This double-blind, placebo-controlled, multinational, randomized study included 116 subjects divided into sequential dose-escalation cohorts, each receiving MYO-029 or placebo (Cohort 1 at mg/kg; Cohort 2 3 10 4 30 mg/kg). Safety adverse...
Daily injections into mice of an ammonium sulfate-precipitated immunoglobulin fraction serum from patients with myasthenia gravis were carried out for up to 14 days. The showed reduced amplitudes miniature endplate potentials and numbers acetylcholine receptors at the neuromuscular junctions. Some typical decremental responses on repetitive nerve stimulation, reversal by neostigmine. This represents first evidence a circulating factor in which passive transfer reproduces features disease...
To study the role of humoral factors in pathogenesis myasthenia gravis, we employed passive transfer human serum fractions to mice. Immunoglobulins from 16 patients with gravis were injected into mice daily for one 14 days. Typical myasthenic features reduction amplitude miniature end-plate potentials (mean change more than 50 per cent, P<0.005) or acetylcholine receptors at neuromuscular junctions (or both) produced by immunoglobulin 15 patients. Some showed weakness decremental responses...
Abstract Ultrasound has been used for visualizing peripheral nerve pathology. Our goal was to use ultrasound quantitate the sizes of upper extremity nerves along their length in control subjects and patients with neuropathy. We measured median ulnar cross‐sectional areas (NCSA) arms 190 subjects, including 100 neuropathies 90 controls. found that NCSAs healthy child adult controls were greater increasing height, at proximal sites, sites entrapment. Nerves enlarged all Charcot–Marie–Tooth 1A...
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...
TAR DNA binding protein-43 (TDP-43) is found in ubiquitinated inclusions (UBIs) some frontotemporal dementias (FTD-U). One form of FTD-U, due to mutations the valosin containing protein (VCP) gene, occurs with an inclusion body myopathy (IBMPFD). Since IBMPFD brain has TDP-43 UBIs, we looked for muscle. In normal muscle, present nuclei. additionally as large within UBIs muscle cytoplasm. were also 78% sporadic myositis (sIBM) muscles. and sIBM migrated additional band on immunoblot similar...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which microglia play significant and active role. Recently, rare missense variant (p.R47H) the microglial activating gene TREM2 was found to increase risk of several diseases, including Alzheimer disease. Whether p.R47H factor for ALS not known.To determine whether (rs75932628) assess expression dysregulated disease.Samples DNA from 923 individuals with sporadic 1854 healthy control self-reported as non-Hispanic...
Duchenne muscular dystrophy (DMD) displays a clinical range that is not fully explained by the primary DMD mutations. Ltbp4, encoding latent transforming growth factor-β binding protein 4, was previously discovered in genome-wide scan as modifier of murine dystrophy. We sought to determine whether LTBP4 genotype influenced severity large patient cohort.
<h3>Objective:</h3> To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. <h3>Methods:</h3> We performed a retrospective review patients referred neuromuscular to identify who had the same limb suspected brachial plexopathy mononeuropathies, carpal/cubital Ultrasound results were compared diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic evaluation. <h3>Results:</h3>...
Objective To define the genetic landscape of amyotrophic lateral sclerosis (ALS) and assess contribution possible oligogenic inheritance, we aimed to comprehensively sequence 17 known ALS genes in 391 patients from United States. Methods Targeted pooled‐sample sequencing was used identify variants genes. Fragment size analysis ATXN2 C9ORF72 expansion sizes. Genotype–phenotype correlations were made with individual total burden variants. Rare variant associations for risk investigated at both...
We aimed to perform an observational study of age at loss independent ambulation (LoA) and side-effect profiles associated with different glucocorticoid corticosteroid (GC) regimens in Duchenne muscular dystrophy (DMD).We studied 340 participants the Cooperative International Neuromuscular Research Group Natural History Study (CINRG-DNHS). LoA was defined as continuous wheelchair use. Effects prednisone or prednisolone (PRED)/deflazacort (DFZ), administration frequency, dose were analyzed by...
Significance Our study, involving 1,873 patients and 36,370 healthy individuals, is an extensive genome-wide study of myasthenia gravis. association transcriptome-wide analyses identified two signals, namely CHRNA1 CHRNB1 , encoding acetylcholine receptor subunits, which were replicated in independent cohort obtained from the UK Biobank. Identifying these genes confirms potential utility using genetics to identify proteins that are antigenic targets autoantibodies. We confirmed genetic...
<b><i>Background:</i></b> Mitochondrial dysfunction occurs early in the course of ALS, and mitochondria may be an important site for therapeutic intervention. Creatine stabilizes mitochondrial transition pore, is ATP production. In a transgenic mouse model administration creatine prolongs survival preserves motor function neurons. <b><i>Methods:</i></b> The authors conducted randomized double-blind, placebo controlled trial on 104 patients with ALS from 14 sites to evaluate efficacy...