title: Worsening of cardiomyopathy using deflazacort in an animal model rescued by gene therapy.
abstract: We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster. In patients with similar genetic defects, steroids have been largely used to slow down disease progression. Aim of our study was to evaluate the combined effects of steroid treatment and gene therapy on cardiac function. We injected the human delta-sarcoglycan cDNA by adeno-associated virus (AAV) 2/8 by a single intraperitoneal injection into BIO14.6 Syrian hamsters at ten days of age to rescue the phenotype. We then treated the hamsters with deflazacort. Treatment was administered to half of the hamsters that had received the AAV and the other hamsters without AAV, as well as to normal hamsters. Both horizontal and vertical activities were greatly enhanced by deflazacort in all groups. As in previous experiments, the AAV treatment alone was able to preserve the ejection fraction (70±7% EF). However, the EF value declined (52±14%) with a combination of AAV and deflazacort. This was similar with all the other groups of affected animals. We confirm that gene therapy improves cardiac function in the BIO14.6 hamsters. Our results suggest that deflazacort is ineffective and may also have a negative impact on the cardiomyopathy rescue, possibly by boosting motor activity. This is unexpected and may have significance in terms of the lifestyle recommendations for patients.
authors.affiliation: Telethon Institute of Genetics and Medicine, Napoli, Italy.
authors.forename: Ida Luisa
authors.initials: IL
authors.lastname: Rotundo
authors.forename: Stefania
authors.initials: S
authors.lastname: Faraso
authors.forename: Elvira
authors.initials: E
authors.lastname: De Leonibus
authors.forename: Gerardo
authors.initials: G
authors.lastname: Nigro
authors.forename: Carmen
authors.initials: C
authors.lastname: Vitiello
authors.forename: Alessio
authors.initials: A
authors.lastname: Lancioni
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Napoli
authors.forename: Sigismondo
authors.initials: S
authors.lastname: Castaldo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
authors.forename: Fabio
authors.initials: F
authors.lastname: Russo
authors.forename: Giulio
authors.initials: G
authors.lastname: Piluso
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nigro
mesh_terms: D000818:Animals; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy*; D006224:Cricetinae; D000229:Dependovirus / Q000235:genetics; D004452:Echocardiography; D015316:Genetic Therapy; D005822:Genetic Vectors; D008297:Male; D008647:Mesocricetus; D011282:Pregnenediones / Q000627:therapeutic use*; D049031:Sarcoglycans / Q000235:genetics / Q000378:metabolism
chemical_list: D011282:Pregnenediones; D049031:Sarcoglycans; C021988:deflazacort