Preclinical Development of New Therapy for Glycogen Storage Diseases.
Repository Usage Stats
Glycogen storage disease (GSD) consists of more than 10 discrete conditions for which the biochemical and genetic bases have been determined, and new therapies have been under development for several of these conditions. Gene therapy research has generated proof-of-concept for GSD types I (von Gierke disease) and II (Pompe disease). Key features of these gene therapy strategies include the choice of vector and regulatory cassette, and recently adeno-associated virus (AAV) vectors containing tissue-specific promoters have achieved a high degree of efficacy. Efficacy of gene therapy for Pompe disease depend upon the induction of immune tolerance to the therapeutic enzyme. Efficacy of von Gierke disease is transient, waning gradually over the months following vector administration. Small molecule therapies have been evaluated with the goal of improving standard of care therapy or ameliorating the cellular abnormalities associated with specific GSDs. The receptor-mediated uptake of the therapeutic enzyme in Pompe disease was enhanced by administration of β2 agonists. Rapamycin reduced the liver fibrosis observed in GSD III. Further development of gene therapy could provide curative therapy for patients with GSD, if efficacy from preclinical research is observed in future clinical trials and these treatments become clinically available.
Disease Models, Animal
Glycogen Storage Disease
Glycogen Storage Disease Type I
Glycogen Storage Disease Type II
Small Molecule Libraries
More InfoShow full item record
Professor of Pediatrics
The focus of our research has been the development of gene therapy with adeno-associated virus (AAV) vectors, most recently by genome editing with CRISPR/Cas9. We have developed gene therapy for inherited disorders of metabolism, especially glycogen storage disease (GSD) and phenylketonuria (PKU). 1) GSD type Ia: Glucose-6-phosphatase (G6Pase) deficient animals provide models for developing new therapy for GSD type Ia, although early mortality complicates research with both
Associate Professor of Pediatrics
My overall research interests are finding effective treatment for human glycogen storage diseases (GSDs) and other inherited metabolic disorders. My current research focuses on identification of novel therapeutic targets and development of effective therapies for GSD II (Pompe disease), GSD III (Cori disease), and GSD IV (Andersen disease) using cellular and animal disease models. The main therapeutic approaches we are using in our pre-clinical studie
Alphabetical list of authors with Scholars@Duke profiles.
Showing items related by title, author, creator, and subject.
Austin, SL; Brooks, ED; Fyfe, JC; Kishnani, Priya Sunil; Sun, Baodong; Thurberg, BL; Yi, Haiqing; ... (8 authors) (Comp Med, 2016-02)Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications ...
Time trends of incidence of age-associated diseases in the US elderly population: Medicare-based analysis. Akushevich, Igor; Arbeev, Konstantin; Kravchenko, J; Ukraintseva, Svetlana; Yashin, Anatoli I (Age Ageing, 2013-07)OBJECTIVES: time trends of age-adjusted incidence rates of 19 ageing-related diseases were evaluated for 1992-2005 period with the National Long Term Care Survey and the Surveillance, Epidemiology and End RESULTS Registry ...
Lantos, Paul (Infect Dis Clin North Am, 2015-06)Chronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, ...