A5062520190- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Congenital Anomalies and Fetal Surgery
- Genomics and Rare Diseases
- RNA Research and Splicing
- Cerebral Palsy and Movement Disorders
- Cardiomyopathy and Myosin Studies
- Children's Physical and Motor Development
- Adipose Tissue and Metabolism
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- Nuclear Structure and Function
- Regulation of Appetite and Obesity
- Virus-based gene therapy research
- Prenatal Screening and Diagnostics
- Diabetes and associated disorders
- Mechanical Circulatory Support Devices
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Congenital Diaphragmatic Hernia Studies
- Viral Infections and Immunology Research
Nationwide Children's Hospital
2017-2025
The Ohio State University Wexner Medical Center
2019-2025
The Ohio State University
2017-2024
Arkansas Children's Hospital
2024
University of Arkansas for Medical Sciences
2024
Cure Spinal Muscular Atrophy
2024
Nationwide Mutual Insurance Company (United States)
2023
Battelle
2021
University of Utah
2021
IRCCS Ospedale San Raffaele
2021
BACKGROUND AND OBJECTIVES: Historically, autosomal recessive 5q-linked spinal muscular atrophy (SMA) has been the leading inherited cause of infant death. SMA is caused by absence SMN1 gene, and gene replacement therapy, onasemnogene abeparvovec-xioi, was Food Drug Administration approved in May 2019. Approval included all children with age <2 years without end-stage weakness. However, transfer abeparvovec-xioi only studied ≤8 months. METHODS: In this article, we report key safety...
DMD pathogenic variants for Duchenne and Becker muscular dystrophy are detectable with high sensitivity by standard clinical exome analyses of genomic DNA. However, up to 7% mutations deep intronic analysis muscle-derived RNA is an important diagnostic step patients who have negative testing but abnormal dystrophin expression in muscle. In this study, muscle biopsies were evaluated from 19 features a dystrophinopathy, mutation analysis. Reverse transcription-polymerase chain reaction or...
Spinal muscular atrophy (SMA) is an autosomal recessive progressive neurodegenerative primary motor neuron disorder caused by biallelic variants of the survival 1 (
Sleep-related symptoms in myotonic dystrophy type 1 (DM1) are often unrecognized. This study aimed to integrate two sleep questionnaires into an outpatient clinic for assessing disturbances DM1 patients, while also developing a pediatric version of one questionnaire. We administered adult and patients with DM1: (1) the Epworth Sleepiness Scale (ESS), which assesses likelihood falling asleep under specific circumstances; (2) Functional Outcomes Sleep Questionnaire-10 (FOSQ-10), evaluates...
Therapeutic exon skipping as a treatment for Duchenne muscular dystrophy (DMD) has largely concentrated on the delivery of antisense oligomers to treat out-of-frame deletions. Here we report preclinical development an adeno-associated virus (AAV)-encapsidated viral vector containing four copies noncoding U7 small nuclear RNA (U7snRNA), each targeted either splice donor or acceptor sites DMD 2. We have previously shown that this (scAAV9.U7.ACCA) Dup2 mouse model results in expression...
Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping these patients has the potential to be highly therapeutic through restoration full-length dystrophin expression. We conducted 48-week open label study casimersen and golodirsen 3 subjects with an 45 or 53 duplication. Two (aged 18 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, cardiac function appeared stable 2 whom they could evaluated. Dystrophin expression...
ABSTRACT Background Nusinersen and risdiplam are U.S. Food Drug Administration (FDA)‐approved treatments for spinal muscular atrophy (SMA). No head‐to‐head clinical trials to assess efficacy exist. Observational studies needed determine if transitioning is safe efficacious. Methods This retrospective study at Nationwide Children's Hospital included individuals with SMA treated nusinersen who switched risdiplam. Motor, pulmonary bulbar function were assessed before 2 years after initiation....
The composition of the beta-cell exocytic machinery is very similar to that neuronal synapses, and developmental pathway beta-cells neurons substantially overlap. beta-Cells secrete gamma-aminobutyric acid express proteins that, in brain, are specific markers inhibitory synapses. Recently, coculture experiments have identified three families synaptic cell-surface molecules (neurexins, neuroligins, SynCAM) drive synapse formation vitro control differentiation nascent synapses into either...
Abstract Next-generation sequencing is a powerful diagnostic tool, yet it has proven inadequate to establish diagnosis in all cases of congenital hypotonia or childhood onset weakness. We sought describe the impact whole exome (WES), which only recently become widely available clinically, on molecular Nationwide Children's Hospital Neuromuscular clinics. reviewed records patients our clinic with pediatric symptoms who had WES done since 2013. Patients were included if clinical suspicion was...
In a phase 1/2, open-label dose escalation trial, we delivered rAAVrh74.MCK.GALGT2 (also B4GALNT2) bilaterally to the legs of two boys with Duchenne muscular dystrophy using intravascular limb infusion. Subject 1 (age 8.9 years at dosing) received 2.5 × 1013 vector genome (vg)/kg per leg (5 vg/kg total) and subject 2 6.9 5 (1 1014 total). No serious adverse events were observed. Muscle biopsy evaluated 3 or 4 months post treatment versus baseline showed evidence GALGT2 gene expression...
Implementation of newborn screening for spinal muscular atrophy (SMA) in 33 US states and increased genetic carrier have led to an increase early, presymptomatic diagnosis SMA. Early treatment is critically important recommended infants with two four copies survival motor neuron 2. Currently, no specific recommendations exist preterm The Food Drug Administration does not recommend using onasemnogene abeparvovec-xioi infants. Some insurance companies interpret "preterm" be less than 40 weeks...
Objective: This report summarizes the key discussions from “Early Care (0–3 years) in Duchenne Muscular Dystrophy” meeting, which aimed to address challenges and opportunities diagnosis care of muscular dystrophy (DMD) female carriers within 0–3-year age group. Methods: The meeting brought together experts healthcare providers who shared insights, discussed advancements DMD care, identified research needs. Presentations covered diagnostic challenges, approved therapies, clinical trials,...