Short-term treatment using insulin-like growth factor-1 (IGF-1) improves life expectancy of the delta-sarcoglycan deficient hamster.
BACKGROUND
The hamster strain CHF147 presents a progressive dilated cardiomyopathy (DCM) due to a large deletion of the delta-sarcoglycan gene that leads to heart failure. This cardiomyopathy induces premature death. We have previously shown that a short-term treatment using IGF-1 preserves cardiac structure and improves function of the CHF147 hamster.


METHODS
In the current study, we measured long-term effects of short-term treatment with recombinant human IGF-1 (rhIGF-1) in CHF147 hamsters. CHF147 hamsters (7-8 months old) were implanted under the skin with an osmotic pump filled either with saline or with recombinant human IGF-1 at a total dose of 25 microg. The osmotic pump allowed a continuous delivery of the protein for a mean duration of 19 days.


RESULTS
We observed a significant increase in overall survival, as well as preservation of cardiac function, in the rhIGF-1-treated group. At the time of death, hearts of treated animals did not present any macroscopical or histological differences compared to those of sham hamsters. These results show that rhIGF-1 treatment slows down the evolution of the DCM in the CHF147 hamster. Moreover, the low dose treatment did not increase IGF-1 serum levels.


CONCLUSIONS
This study is the first one reporting beneficial effects of IGF-1 treatment on survival of an animal model presenting DCM. Our results raise hopes for a new therapeutic approach of this pathology.
Serose
Armelle
A
Institut de Myologie, Institut National de la Santé et de la Recherche Médicale, U582, Université Pierre et Marie Curie, AP HP, CHU Pitié-Salpêtrière, IFR 14, Paris, France.
Salmon
André
A
Fiszman
Marc Y
MY
Fromes
Yves
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy; D006224:Cricetinae; D004452:Echocardiography; D004562:Electrocardiography; D017353:Gene Deletion; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008017:Life Expectancy; D008136:Longevity / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D049031:Sarcoglycans / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors
D011994:Recombinant Proteins; D049031:Sarcoglycans; D007334:Insulin-Like Growth Factor I