Web of Science: 7 citations, Scopus: 8 citations, Google Scholar: citations,
Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes : 8-Year Follow-Up in Dogs
Jaén, Maria Luisa (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Vilà, Laia (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Elias, Ivet (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Jimenez, Veronica (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Rodó, Jordi (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Maggioni, Luca (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Ruiz de Gopegui i Fernández, Rafael (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Garcia, Miguel (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Muñoz, Sergio (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Callejas, David (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Ayuso, Eduard (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Ferré, Tura (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Grifoll, Iris (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Andaluz Martínez, Anna (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Ruberte, Jesus (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Haurigot, Virginia (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)
Bosch i Tubert, Fàtima (CIBER de Diabetes y Enfermedades Metabólicas Asociadas)

Date: 2017
Abstract: Diabetes is a complex metabolic disease that exposes patients to the deleterious effects of hyperglycemia on various organs. Achievement of normoglycemia with exogenous insulin treatment requires the use of high doses of hormone, which increases the risk of life-threatening hypoglycemic episodes. We developed a gene therapy approach to control diabetic hyperglycemia based on co-expression of the insulin and glucokinase genes in skeletal muscle. Previous studies proved the feasibility of gene delivery to large diabetic animals with adeno-associated viral (AAV) vectors. Here, we report the long-term (∼8 years) follow-up after a single administration of therapeutic vectors to diabetic dogs. Successful, multi-year control of glycemia was achieved without the need of supplementation with exogenous insulin. Metabolic correction was demonstrated through normalization of serum levels of fructosamine, triglycerides, and cholesterol and remarkable improvement in the response to an oral glucose challenge. The persistence of vector genomes and therapeutic transgene expression years after vector delivery was documented in multiple samples from treated muscles, which showed normal morphology. Thus, this study demonstrates the long-term efficacy and safety of insulin and glucokinase gene transfer in large animals and especially the ability of the system to respond to the changes in metabolic needs as animals grow older.
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Diabetes ; Adeno-associated viral vectors ; Dogs ; Gene therapy ; Long-term ; Insulin ; Glucokinase
Published in: Molecular therapy. Methods & clinical development, Vol. 6 (april 2017) , p. 1-7, ISSN 2329-0501

PMID: 28626777
DOI: 10.1016/j.omtm.2017.03.008


7 p, 1.3 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2018-02-08, last modified 2019-11-06



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