A5061713867- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Genetics and Neurodevelopmental Disorders
- Trypanosoma species research and implications
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Pancreatic function and diabetes
- Child Nutrition and Feeding Issues
- Neurogenetic and Muscular Disorders Research
- Virus-based gene therapy research
- Autoimmune and Inflammatory Disorders Research
- Glycosylation and Glycoproteins Research
- Neurological disorders and treatments
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Neonatal Health and Biochemistry
- Genomics and Rare Diseases
- Liver Disease Diagnosis and Treatment
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Cystic Fibrosis Research Advances
- Folate and B Vitamins Research
- Biosensors and Analytical Detection
Duke Medical Center
2015-2024
Duke University Health System
2015-2024
Duke University
2012-2023
University of Washington
2023
Children's Hospital of Eastern Ontario
2023
UCSF Benioff Children's Hospital
2023
University of California, San Francisco
2023
University of Ottawa
2023
Ottawa Hospital
2023
Duke University Hospital
2006-2022
Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid alpha-glucosidase (GAA). Infantile-onset characterized by cardiomyopathy, respiratory and skeletal muscle weakness, early death. The safety efficacy recombinant human (rh) GAA were evaluated in 18 patients with rapidly progressing infantile-onset disease.Patients diagnosed at 6 months age younger exhibited severe cardiomyopathy. Patients received IV infusions rhGAA 20 mg/kg (n = 9) or...
Abstract Enzyme replacement therapy (ERT) for Pompe disease using recombinant acid alpha‐glucosidase (rhGAA) has resulted in increased survival although the clinical response is variable. Cross‐reactive immunological material (CRIM)‐negative status been recognized as a poor prognostic factor. CRIM‐negative patients make no GAA protein and develop sustained high antibody titers to ERT that render treatment ineffective. Antibody are generally low majority of CRIM‐positive there typically...
Liver delivery of engineered GAA transgenes to mice with Pompe disease rescued glycogen accumulation in multiple tissues.
Glycogen storage disease (GSD) types VI and IX are rare diseases of variable clinical severity affecting primarily the liver. GSD is caused by deficient activity hepatic glycogen phosphorylase, an enzyme encoded PYGL gene. phosphorylase kinase (PhK), subunits which various genes: ɑ (PHKA1, PHKA2), β (PHKB), ɣ (PHKG1, PHKG2), δ (CALM1, CALM2, CALM3). have a wide spectrum manifestations often cannot be distinguished from each other, or other liver GSDs, on presentation alone. Individuals with...
Objective Although enzyme replacement therapy (ERT) is a highly effective therapy, CRIM-negative (CN) infantile Pompe disease (IPD) patients typically mount strong immune response which abrogates the efficacy of ERT, resulting in clinical decline and death. This study was designed to demonstrate that tolerance induction (ITI) prevents or diminishes development antibody titers, better outcome compared CN IPD treated with ERT monotherapy. Methods We evaluated safety, feasibility algorithm...
Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of utero enzyme-replacement (ERT) a fetus CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive disease cardiomyopathy two previously affected deceased siblings. After receiving ERT standard postnatal therapy, current patient had normal cardiac...
Glucokinase catalyzes a rate-limiting step in glucose metabolism hepatocytes and pancreatic β cells is considered the "glucose sensor" for regulation of insulin secretion. Patients with maturity-onset diabetes young (MODY) have heterozygous point mutations glucokinase gene that result reduced enzymatic activity decreased However, it remains unclear whether abnormal liver contributes to MODY disease. Here we show disruption results phenotype similar mice. Reduced islet causes mildly elevated...
Newborn screening for lysosomal storage diseases (LSDs) has been gaining considerable interest owing to the availability of enzyme replacement therapies. We present a digital microfluidic platform perform rapid, multiplexed enzymatic analysis acid α-glucosidase (GAA) and α-galactosidase screen Pompe Fabry disorders. The results were compared with those obtained using standard fluorometric methods.We performed bench-based, on 60 deidentified newborn dried blood spots (DBSs), plus 10...
<h3>Importance</h3> X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal genetic disorder in which an accumulation of very long-chain fatty acids leads to inflammatory demyelination the central nervous system and adrenal cortex atrophy. In 2016, X-ALD was added US Recommended Uniform Screening Panel. <h3>Objective</h3> To evaluate performance single-tier newborn screening assay for North Carolina. <h3>Design, Setting, Participants</h3> This diagnostic study all dried blood spot specimens...
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
AMP-activated protein kinase (AMPK) regulatory gamma2 subunit (PRKAG2) mutations cause a human cardiomyopathy with cardiac hypertrophy, preexcitation, and glycogen deposition. PRKAG2 is recapitulated in transgenic mice overexpressing mutant N488I the heart (TGgamma2N488I). AMPK heterotrimeric consisting of 1 catalytic (alpha) 2 (beta gamma) subunits. Two alpha-subunit isoforms, alpha1 alpha2, are expressed heart; however, contribution utilization these subunits to unknown. Mice...