A5037406350- Muscle Physiology and Disorders
- Bayesian Methods and Mixture Models
- Advanced Statistical Methods and Models
- Statistical Methods and Bayesian Inference
- Statistical Methods and Inference
- Advanced Clustering Algorithms Research
- Cardiomyopathy and Myosin Studies
- Genomics and Phylogenetic Studies
- Muscle metabolism and nutrition
- Genetic Neurodegenerative Diseases
- Muscle activation and electromyography studies
- Exercise and Physiological Responses
- Children's Physical and Motor Development
- Spectroscopy and Chemometric Analyses
- Adrenal Hormones and Disorders
- Statistical Distribution Estimation and Applications
- Inflammatory Myopathies and Dermatomyositis
- Transcranial Magnetic Stimulation Studies
- Hormonal Regulation and Hypertension
- Stress Responses and Cortisol
- Neurogenetic and Muscular Disorders Research
- Telomeres, Telomerase, and Senescence
- COVID-19 epidemiological studies
- Advanced Biosensing Techniques and Applications
- Sensory Analysis and Statistical Methods
Carleton University
2021-2025
Duke University
2024
Newcastle University
2024
Binghamton University
2014-2023
American Red Cross
2023
Johnson City Medical Center
2019
McMaster University
2015-2016
University of Guelph
2010-2011
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).
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...
<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...
Summary An expanded family of mixtures multivariate power exponential distributions is introduced. While fitting heavy-tails and skewness have received much attention in the model-based clustering literature recently, we investigate use a distribution that can deal with both varying tail-weight peakedness data. A parsimonious models proposed using an eigen-decomposition scale matrix. generalized expectation–maximization algorithm presented combines convex optimization via...
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...
Extensive biomarker discoveries for DMD have occurred in the past 7 years, and a vast array of these biomarkers were confirmed independent cohorts across different laboratories. In previous studies, glucocorticoids age two major confounding variables. this new study, using SomaScan technology focusing on subset young patients who not yet treated with glucocorticoids, we identified 108 elevated 70 decreased proteins relative to matched healthy controls (p value < 0.05 after adjusting multiple...
Lung cancer is the leading cause of cancer-related death in Unites States, and approximately 85% all lung cancers are classified as non-small cell (NSCLC), which extremely difficult to treat its survival rate low. After decades clinical trials, most effective treatments still those that implement first-generation platinum anticancer agent cisplatin (CDDP) combination with other drugs. We previously demonstrated naturally-occurring compound phenethyl isothiocyanate (PEITC) can be used...
Duchenne muscular dystrophy (DMD) is caused by pathogenic variants of the DMD gene, leading to loss dystrophin. Clinical variability in can complicate interpretation interventional data clinical trials. One source allelic heterogeneity (different with different effects on dystrophin protein expression). We sought determine whether gene variant classes trial participants potentially affect interpretation. analyzed 186 vamorolone (VBP15-002/003; VBP15-004) who were 4 <7 years old and...
Multiple definitions have been used to identify individuals who are high system users (HSUs), through economic costs, frequency of use, or length stay for inpatient care users. However, no definition has validated be representative those residing in rural communities, face unique service accessibility. This paper identifies an HSU Canada that is inclusive various levels rurality, longitudinal patient experiences, and types hospitalizations experienced. study utilized the 2011 Canadian Census...
Abstract Background Blood accessible biomarkers to assess disease activity and their response therapies in Juvenile Dermatomyositis (JDM) are urgently needed. This pilot study aims identify serum protein associated with clinical untreated JDM medical therapy. Methods SomaScan® technology screened patients for 1305 proteins at three points: 1) before start of treatment, 2) while on therapy, 3) after treatment tapering when were clinically inactive. To define biomarkers, data from ( n = 8)...
Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin in muscle, and while all patients share the primary gene biochemical defect, there considerable patient-patient variability clinical symptoms. We sought to develop multivariate models serum protein biomarkers that explained observed variation, using functional outcome measures as proxies for severity. Serum samples from 39 steroid-naïve DMD boys 4 <7 years enrolled into a trial vamorolone were studied (NCT02760264). Four...
Recently, the Food and Drug Administration granted accelerated approvals for four exon skipping therapies -Eteplirsen, Golodirsen, Viltolarsen, Casimersen -for Duchenne Muscular Dystrophy (DMD). However, these treatments have only demonstrated variable largely sub-therapeutic levels of restored dystrophin protein in DMD patients, limiting their clinical impact. To better understand expression behavior truncated vivo, we assessed turnover dynamics glycoprotein complex (DGC) proteins mdx mice...
Duchenne muscular dystrophy (DMD) exhibits substantial variability in rates of disease progression and response to treatment. This has hindered treatment development complicated interpretation drug effects clinical trials.We hypothesized that a multivariate combination early-age outcome measurements can explain differential progression.Data on boys with DMD (ages 4-<10 years), both treated steroidal anti-inflammatories untreated, were obtained from CINRG Natural History Study (n = 209)...
Whole genome duplication (WGD), the doubling of nuclear DNA a species, contributes to biological innovation by creating genetic redundancy. One mode WGD is allopolyploidization, wherein each from two ancestral species becomes 'subgenome' polyploid descendant species. The evolutionary trajectory duplicated gene that arises influenced both natural selection may favour redundant, new or partitioned functions, and silencing (pseudogenization). Here, we explored how these phenomena varied over...
Duchenne muscular dystrophy is initiated by dystrophin deficiency, but downstream pathophysiological pathways such as membrane instability, NFĸB activation, mitochondrial dysfunction, and induction of TGFβ fibrosis are thought to drive the disability. Dystrophin replacement strategies hopeful for addressing upstream deficiency; however, all methods date use semi-functional proteins that likely trigger pathways. Thus, combination therapies can target multiple important in treating DMD, even...
Duchenne muscular dystrophy (DMD) is a progressive muscle disease involving complex skeletal pathogenesis. The pathogenesis triggered by sarcolemma instability due to the lack of dystrophin protein expression, leading Ca2+ influx, fiber apoptosis, inflammation, necrosis, and fibrosis. Our lab recently used two high-throughput multiplexing techniques (e.g., SomaScan® aptamer assay tandem mass tag-(TMT) approach) identified series serum biomarkers tied different pathobiochemical pathways. In...
Background: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. Objective: A 3-year, longitudinal, prospective dataset contributed by patients confirmed was analyzed to characterize the natural history this disorder. better understanding crucial rigorous therapeutic trials. Methods: cohort 83 (5–75 years at baseline) were followed for up 3 annual assessments. Muscle pulmonary function...
Abstract Human genetic variation (polymorphisms) in genes coding proteins involved the absorption, distribution, metabolism, and elimination (ADME) of drugs can have a strong effect on drug exposure downstream efficacy safety outcomes. Vamorolone, dissociative steroidal anti‐inflammatory for treating Duchenne muscular dystrophy (DMD), primarily undergoes oxidation by CYP3A4 CYP3A5 glucuronidation UDP‐glucuronosyltransferases. This work assesses pharmacokinetics (PKs) vamorolone sources...