A5075594131- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Virus-based gene therapy research
- Muscle metabolism and nutrition
- Force Microscopy Techniques and Applications
- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Tissue Engineering and Regenerative Medicine
- Genetic Neurodegenerative Diseases
- Hormonal and reproductive studies
- Neurogenetic and Muscular Disorders Research
- Cardiovascular Effects of Exercise
- Muscle activation and electromyography studies
- Nutrition and Health in Aging
- CRISPR and Genetic Engineering
- Cellular Mechanics and Interactions
- Mitochondrial Function and Pathology
- Silk-based biomaterials and applications
- Pluripotent Stem Cells Research
- Genetics and Physical Performance
- Autism Spectrum Disorder Research
- Estrogen and related hormone effects
- Zebrafish Biomedical Research Applications
- Telomeres, Telomerase, and Senescence
- Viral Infectious Diseases and Gene Expression in Insects
Solidus Biosciences (United States)
2017-2023
Kaiser Permanente Washington Health Research Institute
2020
Kaiser Permanente
2019
Group Health Cooperative
2015-2018
Pfizer (United States)
2010-2017
Rare Disease Therapeutics (United States)
2017
Community Connections
2016
Analysis Group (United States)
2016
University of Pennsylvania
2002-2015
Dana-Farber Cancer Institute
2010
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, membrane-stabilizing protein encoded DMD gene. Although mouse models provide insight into potential corrective therapy, data from genetically homologous large animals, such as dystrophin-deficient golden retriever (GRMD) model, may more readily translate to humans. To evaluate clinical translatability an adeno-associated virus serotype 9 vector (AAV9)–microdystrophin (μDys5)...
The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only small proportion patients resulting in an urgent need therapies that benefit all regardless underlying mutation. Myostatin is member transforming growth factor-β (TGF-β) family ligands and negative regulator mass. Loss myostatin has been shown to increase mass improve function both normal dystrophic mice. Therefore, blockade via specific antibody...
Myosin V is a two-headed molecular motor that binds six light chains per heavy chain, which creates unusually long lever arms. This moves processively along its actin track in discrete 36-nm steps. Our model one head of the myosin tightly to and swings arm through large angle, providing stroke. We created single-headed constructs with different-size arms show stroke size proportional length. In molecule, provides directional bias, after unbound diffuses find binding site, 36 nm forward....
Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid development new therapies, monitoring progression and response to therapy.The goal this study was evaluate a panel serum protein with potential specifically detect skeletal muscle injury.Serum concentrations troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding (FABP3) muscle-type creatine kinase (CKM) proteins were measured...
High variability in patients' changes 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory aged 5 years or older genetically confirmed who were enrolled a natural history study at 11 care centers throughout Italy included. For each boy, standardized assessments 6MWD...
The regulation of cross-bridge transition from weakly attached to force-bearing states was studied at 10 degrees C in skinned muscle fibers by measuring the rate force development after a quick release-restretch cycle (ktr), decline (kPi) photogeneration Pi caged Pi, and stiffness presence absence an inhibitor strong formation, 2,3-butanedione monoxime (BDM). Both BDM suppressed more than stiffness. However, reduction Ca2+ parallel fashion. ktr kPi were reversibly reduced (by 30-35%) 3 mM...
To identify the frequency of and factors associated with changes in employment among cancer survivors.This prospective cohort study took place context population-based Cancer Care Outcomes Research Surveillance Consortium. Patients nonmetastatic lung or colorectal who survived approximately 15 months after diagnosis without recurrence provided their self-reported status, experiences, insurance coverage at 4 diagnosis. Multiple logistic regression was used to relate sociodemographic disease...
Testosterone (T) supplementation increases skeletal muscle mass, circulating GH, IGF-I, and im IGF-I expression, but the role of GH in mediating T's effects on remains poorly understood. Here, we show that T administration increased body weight mass androgen-dependent levator ani hypophysectomized as well castrated plus adult male rats. stimulated proliferation primary human cells (hSKMCs) vitro, an effect blocked by transfecting hSKMCs with small interference RNA targeting receptor...
Abstract Safety, tolerability, anabolic effects, pharmacokinetics, and pharmacodynamics of single ascending multiple doses domagrozumab, an antimyostatin monoclonal antibody, were assessed following intravenous (IV) subcutaneous (SC) administration in healthy subjects. A range dose levels between 1 40 mg/kg IV (3 doses) 10 tested (n = 8 per cohort). Additionally, a 3 SC 8) cohort also received domagrozumab. Magnetic resonance imaging whole‐body dual‐energy x‐ray absorptiometry conducted to...
Duchenne muscular dystrophy (DMD) is a serious, rare genetic disease, affecting primarily boys. It caused by mutations in the DMD gene and characterized progressive muscle degeneration that results loss of function early death due to respiratory and/or cardiac failure. Although limited treatment options are available, some for only small subsets patient population, remains disease with large unmet medical needs. The adeno-associated virus (AAV) vector leading delivery system addressing...
1 Measurements of the unloaded sliding speed and isometric force exerted on single thin filaments in vitro motility assays were made to evaluate role regulatory proteins control filament production. 2 Regulated actin reconstituted from rabbit F-actin, native bovine cardiac tropomyosin (nTm), either troponin (nTn), containing a TnC mutant, CBMII, which sole site (site II) is inactivated (CBMII-Tn), or point mutation TnT (I79N, where isoleucine at position 79 replaced with asparagine)...
Skeletal muscle atrophy can be a consequence of many diseases, environmental insults, inactivity, age, and injury. Atrophy is characterized by active degradation, removal contractile proteins, reduction in fiber size. Animal models have been extensively used to identify pathways that lead atrophic conditions. We genome-wide expression profiling analyses quantitative PCR the molecular changes occur two clinically relevant mouse atrophy: hindlimb casting Achilles tendon laceration (tenotomy)....
Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity non-human-derived antibodies, which can be a major limitation development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. retention foreign content in the CDR regions, however, is still potential immunogenic liability....
Objectives Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that causes progressive weakness and early death. Gene therapy an area of new therapeutic development. This qualitative study explored factors influencing parents' adult patients' preferences about gene therapy. Methods We report data from 17 parents children with DMD 6 patients. Participants responded to hypothetical vignette features including non-curative stabilizing benefits muscle, cardiac pulmonary function;...
Abstract Background Multiple clinical trials to assess the efficacy of AAV-directed gene transfer in participants with Duchenne muscular dystrophy (DMD) are ongoing. The success these currently relies on standard functional outcome measures that may exhibit variability within and between participants, rendering their use as sole drug challenging. Given this, supportive objective biomarkers be useful enhancing observed results. Creatine kinase (CK) is traditionally used a diagnostic biomarker...
Abstract Duchenne muscular dystrophy (DMD) is caused by a lack of the dystrophin protein and has no effective treatment at present. Zebrafish provide powerful in vivo tool for high-throughput therapeutic drug screening improvement muscle phenotypes deficiency. Using dystrophin-deficient zebrafish, sapje, we have screened total 2640 compounds with known modes action from three libraries to identify modulators disease progression. Six that target heme oxygenase signaling were found rescue...
Several gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers patients prioritize factors influencing regarding participation early-phase trials.We conducted a best-worst scaling experiment among U.S. adults with (N = 274). Participants completed 11 choice sets, choosing features they cared about most least when deciding whether...