A5050280688- Muscle Physiology and Disorders
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- Virus-based gene therapy research
- Genetic Neurodegenerative Diseases
- Lysosomal Storage Disorders Research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Inflammatory Myopathies and Dermatomyositis
- RNA Interference and Gene Delivery
- Cerebral Palsy and Movement Disorders
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Biotin and Related Studies
- Children's Physical and Motor Development
- Genomics and Rare Diseases
- Viral Infections and Immunology Research
- Hereditary Neurological Disorders
- Muscle activation and electromyography studies
- Neurological diseases and metabolism
- Cardiovascular Effects of Exercise
- Advanced biosensing and bioanalysis techniques
Nationwide Children's Hospital
2016-2025
The Ohio State University
2015-2024
The Ohio State University Wexner Medical Center
2017-2024
St. Jude Children's Research Hospital
2024
Nationwide Mutual Insurance Company (United States)
2012-2023
University of Bonn
2023
Institut de Recerca Sant Joan de Déu
2023
University of Utah
2006-2021
IRCCS Ospedale San Raffaele
2021
Columbus Center
2019
Abstract Objective: Creatine kinase (CK) levels are increased on dried blood spots in newborns related to the birthing process. As a marker for newborn screening, CK Duchenne muscular dystrophy (DMD) results false‐positive testing. In this report, we introduce 2‐tier system using spot first assess with follow‐up DMD gene Methods: A fluorometric assay based upon enzymatic transphosphorylation of adenosine diphosphate triphosphate was used measure activity. Preliminary studies established...
In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51. The present study used double-blind placebo-controlled protocol test eteplirsen's ability induce and improve distance walked on the 6-minute walk (6MWT).DMD boys aged 7 13 years, confirmed deletions correctable by 51 200 400 m 6 MWT, were randomized weekly intravenous infusions of 30 or 50...
Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, improved clinical care. Locus-specific databases allow collection, organization, storage, analysis genetic variants disease. Here, we describe development TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed data 7,149 held within database. A total 5,682 large were observed (80%...
The primary muscle disorders are a diverse group of diseases caused by various defective structural proteins, abnormal signaling molecules, enzymes and proteins involved in posttranslational modifications, other mechanisms. Although there is increasing clarification the aberrant cellular processes responsible for these conditions, decisive factors secondary pathogenic cascades still mainly obscure. Given emerging roles microRNAs (miRNAs) modulation phenotypes, we searched miRNAs regulated...
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...
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...
The objective of this study was to establish the feasibility long-term gentamicin dosing achieve stop codon readthrough and produce full-length dystrophin. Mutation suppression codons, successfully achieved in mdx mouse using gentamicin, represents an important evolving treatment strategy Duchenne muscular dystrophy (DMD).Two DMD cohorts received 14-day (7.5mg/kg/day): Cohort 1 (n = 10) patients 2 8) frameshift controls. Two additional were treated (7.5mg/kg) for 6 months: 3 12) dosed weekly...
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...
Becker muscular dystrophy (BMD) is a variant of dystrophin deficiency resulting from DMD gene mutations. Phenotype variable with loss ambulation in late teenage or mid-life years. There currently no treatment for this condition. In BMD proof-of-principle clinical trial, potent myostatin antagonist, follistatin (FS), was used to inhibit the pathway. Extensive preclinical studies, using adeno-associated virus (AAV) deliver follistatin, demonstrated an increase strength. For we alternatively...
Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen dosage.To compare efficacy adverse effects of 3 most frequently prescribed corticosteroid regimens dystrophy.Double-blind, parallel-group randomized clinical trial including 196 aged 4 to 7 years dystrophy who had not previously been treated corticosteroids; enrollment occurred between January 30, 2013, September 17, 2016, at 32 clinic sites 5...
As a result of their ability to induce translational readthrough stop codons, the aminoglycoside antibiotics are currently being tested for efficacy in treatment Duchenne muscular dystrophy patients carrying nonsense mutation dystrophin gene. We have undertaken systematic analysis aminoglycoside-induced each codon human tissue culture cells using dual luciferase reporter system. Significant differences efficiency were observed, with UGA showing greater than UAG or UAA. Additionally,...
Abstract Objective: The aim of this study was to attain long‐lasting alpha‐sarcoglycan gene expression in limb‐girdle muscular dystrophy, type 2D (LGMD2D) subjects mediated by adeno‐associated virus (AAV) transfer under control a muscle specific promoter (tMCK). Methods: rAAV1.tMCK.hSGCA (3.25 × 10 11 vector genomes) delivered the extensor digitorum brevis 3 with documented SGCA mutations via double‐blind, randomized, placebo controlled trial. Control sides received saline. blind not broken...
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.
This study determined the relative efficacy of an experimental explicit emergent literacy intervention program for preschoolers experiencing multiple risk factors. Using alternating treatment research design, children completed two 6-week waves in small groups; one wave featured program, whereas other a comparison program. Emergent assessment was conducted at pretest and end each wave. Results indicated significant widespread gains knowledge over entire 12-week program; growth significantly...
We investigated the possible mechanisms of paralysis and recovery in a patient with acute motor axonal neuropathy (AMAN) pattern Guillain-Barré syndrome. The AMAN GBS is characterized clinically by without sensory involvement electrodiagnostically low compound action potential amplitudes, suggesting damage, evidence demyelination. Many patients have serologic or culture recent Campylobacter jejuni infection. Pathologically, most severe cases are wallerian-like degeneration axons affecting...
<b>Background: </b> Axonal neuropathy linked to the CMT2A locus was originally associated with a mutation in KIF1B gene. However, mutations this gene have not been described any other families. Recently, MFN2 gene, encoding mitochondrial GTPase mitofusin 2 (Mfn2), identified as causative of seven The authors report three additional families novel highly conserved regions Mfn2 domain. <b>Methods: performed standardized neuromuscular and nerve conduction examination, genotyped known CMT loci,...
Mutations affecting the seemingly unrelated gene products, SepN1, a selenoprotein of unknown function, and RyR1, major component ryanodine receptor intracellular calcium release channel, result in an overlapping spectrum congenital myopathies. To identify immediate developmental molecular roles SepN RyR vivo, loss-of-function effects were analyzed zebrafish embryo. These studies demonstrate two proteins are required for same cellular differentiation events needed normal fluxes is physically...