A5060212143- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Virus-based gene therapy research
- Neurological diseases and metabolism
- Muscle activation and electromyography studies
- Adipose Tissue and Metabolism
- Silk-based biomaterials and applications
- Congenital heart defects research
- Veterinary Orthopedics and Neurology
- Metabolism and Genetic Disorders
- Nerve injury and regeneration
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- Muscle metabolism and nutrition
- Electrospun Nanofibers in Biomedical Applications
- Genetic Neurodegenerative Diseases
- Exercise and Physiological Responses
- Veterinary Oncology Research
- CRISPR and Genetic Engineering
- Cardiomyopathy and Myosin Studies
- Fetal and Pediatric Neurological Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Peripheral Nerve Disorders
- Calpain Protease Function and Regulation
- Biotin and Related Studies
Texas A&M University
2015-2024
Mitchell Institute
2015-2018
University of North Carolina at Chapel Hill
2008-2016
University of Pennsylvania
2016
Vanderbilt University Medical Center
2016
Indiana University School of Medicine
2010-2014
Gene Therapy Laboratory
2014
Communities In Schools of Orange County
2012
North Carolina State University
1988-2011
University of Georgia
1978-2011
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)...
Abstract Clinicopathologic findings from two golden retriever dogs with an inherited, progressive, degenerative muscle disease that were studied until 27 and 40 months of age are described. Initial clinical signs included stilted gait simultaneous advancement their pelvic limbs. Further restriction hypertrophy eventually occurred. Serum creatine kinase was dramatically elevated (>10,000 U/L). There persistent “spontaneous” high‐frequency discharges (pseudomyotonia) on electromyographic...
A retrospective study of 86 dogs with brain tumors was undertaken. Sixty-nine had histologic confirmation tumor type, whereas the remaining 17 CT evidence a tumor. All neurologic abnormalities. Seven received no treatment, 38 only symptomatic and 41 some form definitive in addition to medical management. Types treatment included surgery, cobalt-60 radiation, whole-body hyperthermia, 125I implants, chemotherapy, alone or combination. The factor that most associated survival duration mode...
The success of many gene therapy applications hinges on efficient whole body transduction. In the case muscular dystrophies, a therapeutic vector has to reach every muscle in body. Recent studies suggest that vectors based adeno-associated virus (AAV) are capable body-wide transduction rodents. However, translating this finding large animals remains challenge. Here we explored systemic delivery with AAV serotype-9 (AAV-9) neonatal dogs. Previous attempts directly deliver adult canine have...
Duchenne (DMD) and golden retriever (GRMD) muscular dystrophy are caused by genetic mutations in the dystrophin gene afflict striated muscles. We investigated systemic delivery 4-day-old GRMD dogs given a single intravenous injection of an AAV9 vector (1.5 × 1014 genomes/kg) carrying human codon-optimized mini-dystrophin under control cytomegalovirus (CMV) promoter. One three treated was euthanized 9 days later due to pre-existing conditions. Scattered mini-dystrophin-positive myofibers were...
Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration caused by lack the cytoskeletal protein dystrophin. Dystrophin deficiency causes membrane instability, skeletal wasting, cardiomyopathy, and heart failure. Advances in palliative respiratory care have increased incidence DMD patients, for which there no cure or effective therapy. Here we shown that chronic infusion membrane-sealing poloxamer to severely affected dystrophic dogs reduced myocardial fibrosis,...
Inhibition or blockade of myostatin, a negative growth factor skeletal muscle, enhances muscle and therefore is considered promising strategy for the treatment muscle-wasting diseases such as muscular dystrophies. Previously, we showed that myostatin in both normal dystrophin-deficient mdx mice by systemic delivery propeptide (MPRO) gene an adeno-associated virus serotype 8 (AAV8) vector could enhance ameliorate dystrophic lesions. Here, further investigate whether effect can be achieved...
Although restoration of dystrophin expression via exon skipping in both cardiac and skeletal muscle has been successfully demonstrated the mdx mouse, large animal models Duchenne muscular dystrophy (DMD) proven to be a challenge. In animals, investigators have focused on using intravenous injection antisense oligonucleotides (AO) mediate skipping. this study, we sought optimize golden retriever (GRMD) model percutaneous transendocardial delivery recombinant AAV6 (rAAV6) deliver modified U7...
The amount and distribution of dystrophin protein in myofibers muscle is highly variable Becker muscular dystrophy exon-skipping trials for Duchenne dystrophy. Here, we investigate a molecular basis this variability. In from patients sharing the same exon 45–47 in-frame deletion, levels negatively correlate with microRNAs predicted to target dystrophin. Seven inhibit expression vitro, three are validated vivo (miR-146b/miR-374a/miR-31). expressed dystrophic increase age disease severity....
The purpose of this study was to develop a strain canine X-linked muscular dystrophy (CXMD), model Duchenne dystrophy, in Japan. A female beagle artificially inseminated with frozen-thawed spermatozoa derived from an affected golden retriever. Subsequently, two carrier dogs (G1 carriers) and four normal male littermates were produced. Thereafter, the G1 carriers mated sires. As result, each bitch whelped three times, out 54 pups, 17 descendants, 11 descendants (G2 detected. One G2 then sire...
Clinical features of 36 dogs with histologically confirmed fibrocartilaginous embolism (FCE) were contrasted those 26 in which FCE was suspected based on characteristic clinical findings and the absence compressive spinal cord disease myelography. Dogs similar signalment, had acute, nonprogressive dysfunction, often associated trauma or exercise. The "suspected" group included fewer giant breeds more asymmetric lesions, intact nociception, upper motor neuron involvement. Dog size severity...
A retrospective study of pathologically confirmed cases feline spinal lymphosarcoma (FSL) admitted to the Colleges Veterinary Medicine at University Georgia and North Carolina State from 1973 1988 was conducted. Two hundred fourteen were diagnosed histopathologically; involvement central nervous system (CNS) identified in 26 (12.1%). Twenty-three these tumors involved cord, 22 23 solitary. predilection for thoracic lumbar vertebral canal noted. Most cats with disease young, mean median ages...
Magnetic resonance images of twenty‐five dogs with histopathologically confirmed primary brain tumors were evaluated. A lesion was visible in each dog. Meningiomas extra‐axial lesions that enhanced markedly withj gadolinium‐DTPA. Glimas Characteized by intra‐axial location, significant mass effect and surrounding edema, variable enhancement patterns. Choroid plexus pituitary differentiated their location marked enbancement. Prediction general typeof tumor correct 24 25 dogs.