Edward C. Smith
A5072936660- Aeroelasticity and Vibration Control
- Muscle Physiology and Disorders
- Vibration Control and Rheological Fluids
- Neurogenetic and Muscular Disorders Research
- Composite Structure Analysis and Optimization
- Magnetic Bearings and Levitation Dynamics
- Analytical Chemistry and Chromatography
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Plant-based Medicinal Research
- Structural Analysis and Optimization
- Lysosomal Storage Disorders Research
- Tribology and Lubrication Engineering
- Vibration and Dynamic Analysis
- Structural Engineering and Vibration Analysis
- Piezoelectric Actuators and Control
- Mechanical Engineering and Vibrations Research
- RNA modifications and cancer
- Systemic Lupus Erythematosus Research
- Cardiomyopathy and Myosin Studies
- Acoustic Wave Phenomena Research
- Hydraulic and Pneumatic Systems
- Botanical Research and Chemistry
- RNA Research and Splicing
- Telomeres, Telomerase, and Senescence
Pennsylvania State University
2015-2024
Duke Medical Center
2015-2024
Duke University
2011-2024
Newcastle University
2024
Carleton University
2024
Leicestershire Partnership NHS Trust
2024
University of Oxford
2023
University College London
2016-2021
University of North Carolina at Chapel Hill
2021
The University of Queensland
2021
An unmet need remains for safe and efficacious treatments Duchenne muscular dystrophy (DMD). To date, there are limited agents available that address the underlying cause of disease.To evaluate safety, tolerability, efficacy viltolarsen, a novel antisense oligonucleotide, in participants with DMD amenable to exon 53 skipping.This phase 2 study was 4-week randomized clinical trial safety followed by 20-week open-label treatment period patients aged 4 9 years skipping. enroll 16 participants,...
Corticosteroidal anti-inflammatory drugs are widely prescribed but long-term use shows adverse effects that detract from patient quality of life.To determine if vamorolone, a structurally unique dissociative steroidal drug, is able to retain efficacy while reducing safety concerns with in Duchenne muscular dystrophy (DMD).Randomized, double-blind, placebo- and prednisone-controlled 24-week clinical trial, conducted June 29, 2018, February 24, 2021, 24 weeks follow-up. This was multicenter...
Vamorolone is a dissociative agonist of the glucocorticoid receptor that has shown similar efficacy and reduced safety concerns in comparison with prednisone Duchenne muscular dystrophy (DMD). This study was conducted to determine vamorolone over 48 weeks crossover participants (prednisone vamorolone; placebo vamorolone).
Journal Article Handbook of Analytical Derivatization Reactions Get access Reactions. Daniel R. Knapp. John Wiley & Sons, New York, NY, 1979. 741 pp. Price $42.50. Edward Smith Division Drug Chemistry Food and Administration Washington, DC 20204 Search for other works by this author on: Oxford Academic Google Scholar Association Official Chemists, Volume 63, Issue 6, 1 November 1980, Page 1363, https://doi.org/10.1093/jaoac/63.6.1363a Published: 22 January 2020
<h3>Objective</h3> To study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD). <h3>Methods</h3> An open-label, multiple-ascending-dose of vamorolone was conducted 48 boys with DMD (age 4–<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d an oral suspension formulation (12 per dose level; one-third to 10 times the glucocorticoid DMD). The primary goal define optimal doses vamorolone. outcome for clinical efficacy...
<h3>Importance</h3> Vamorolone is a synthetic steroidal drug with potent anti-inflammatory properties. Initial open-label, multiple ascending dose-finding studies of vamorolone among boys Duchenne muscular dystrophy (DMD) found significant motor function improvement after 6 months treatment in higher-dose (ie, ≥2.0 mg/kg/d) groups. <h3>Objective</h3> To investigate outcomes 30 open-label treatment. <h3>Design, Setting, and Participants</h3> This nonrandomized controlled trial was conducted...
Duchenne muscular dystrophy (DMD) is a rare, genetic disease caused by mutations in the DMD gene resulting an absence of functional dystrophin protein. Viltolarsen, exon 53 skipping therapy, has been shown to increase endogenous levels. Herein, long-term (>2 years) outcomes viltolarsen treated patients were compared matched historical control group.To evaluate efficacy and safety anti-sense oligonucleotide treatment with amenable therapy.This trial (NCT03167255) extension previously...
Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased levels patients with DMD. Presented here are completed study results > 4 years outcomes viltolarsen-treated compared to a historical control group (Cooperative International Neuromuscular Research Group Natural History Study [CINRG DNHS]). Objective: To evaluate the efficacy and safety...
A low-power, nonthermal, ultrasonic de-icing system is introduced as a potential for helicopter rotor blades. In this research effort, actuators excite isotropic plates and airfoil-shaped structures that are representative of leading-edge protection caps. The generates delaminating transverse shear stresses at the interface accreted ice, debonding thin ice layers (less than 3 mm thick) they form on host structure. finite element model proposed actuator with guides selection prototypes....
Ultrasonic excitation has proven to provide ice-interface transverse shear stresses exceeding the adhesion strength of freezer ice various metals, promoting instantaneous delamination. Wind-tunnel impact presents challenges that are not encountered when removing ice. The low-power, nonthermal ultrasonic de-icing concept is investigated under impact-icing conditions in an icing wind tunnel. In this research effort, actuator disks excite isotropic plates and airfoil-shaped structures...
We report a first-in-patient study of vamorolone, first-in-class dissociative steroidal anti-inflammatory drug, in Duchenne muscular dystrophy. This 2-week, open-label Phase IIa multiple ascending dose (0.25, 0.75, 2.0, and 6.0 mg/kg/day) enrolled 48 boys with dystrophy (4 to <7 years), outcomes including clinical safety, pharmacokinetics pharmacodynamic biomarkers. The design included biomarkers three contexts use: 1. Secondary for safety (insulin resistance, adrenal suppression, bone...
To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens decline in ambulatory ability boys with Duchenne muscular dystrophy (DMD).Three hundred thirty-one participants DMD 7 14 years of age taking glucocorticoids were tadalafil 0.3 mg·kg-1·d-1, 0.6 or placebo. The efficacy measure was 6-minute walk distance (6MWD) after weeks. Secondary measures included North Star Ambulatory Assessment and timed function tests....
Background Treatment with corticosteroids is recommended for Duchenne muscular dystrophy (DMD) patients to slow the progression of weakness. However, chronic corticosteroid treatment causes significant morbidities. Vamorolone a first-in-class anti-inflammatory investigational drug that has shown evidence efficacy in DMD after 24 weeks at 2.0 or 6.0 mg/kg/day. Here, open-label and safety experience vamorolone was evaluated over period 18 months trial participants DMD. Methods findings A...
Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement (ERT) by creating a liver depot acid α-glucosidase (GAA) production. We report initial safety and bioactivity of first dose (1.6 × 10
Abstract Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they abundant myelin membranes. Serine palmitoyltransferase, enzyme that catalyses rate-limiting reaction sphingolipid synthesis, is composed multiple subunits including an activating subunit, SPTSSA. both essential cytotoxic their synthesis must therefore be tightly regulated. Key to homeostatic regulation ORMDL proteins bound serine...
<h3>Background:</h3> Plectin crosslinks intermediate filaments to their targets in different tissues. Defects plectin cause epidermolysis bullosa simplex (EBS), muscular dystrophy (MD), and sometimes pyloric atresia. Association of EBS with a myasthenic syndrome (MyS) was documented single patient 1999. <h3>Objectives:</h3> To analyze the clinical, structural, genetic aspects second fatal case associated MyS search for basis disease previously reported EBS-MD-MyS. <h3>Methods:</h3> Clinical...
The use of ultrasonic excitation has shown the ability to promote ice shedding impact (less than 2 mm thick) during prior wind-tunnel testing efforts. de-icing technology is implemented structures representative rotorcraft blade leading edges and tested under icing centrifugal environments . Finite element models are experimentally validated used predict transverse shear stresses responsible for shedding. finite tools then guide design a robust bondline between lead zirconate titanate...
In this paper, a new damage detection technique able to identify the location of breathing crack in an isotropic rod, relying only on real-time measurements, is proposed.The algorithm exploits phase information associated with superharmonic components produced, Fourier spectrum, by nonlinear dynamic response kind defect under influence external excitation.The validity proposed for weakly system supported analytical solution cracked beam obtained through harmonic balance approach.A numerical...