title: Gene therapy for cardiac cachexia?
abstract: The prevention or attenuation of disease-related skeletal muscle degeneration has been a common goal in the treatment of cardiac cachexia. Cell-based therapies are complicated by insufficient numbers of autologous myoblasts and by ineffective incorporation into host muscle. Pharmacological administration of growth hormone in a variety of clinical conditions characterized by an increase in catabolic rate have been associated with increases in mortality and morbidity, resulting in a decrease in the clinical use of growth hormone and its downstream effector, insulin-like growth factor-1 and a decline in general research into anabolic treatment strategies. In mouse models, however, the selective expression of a muscle-specific transgene encoding a locally acting IGF-1 isoform induces muscle hypertrophy, prevents age- or disease-related atrophy, by increasing stem cell recruitment to injured or degenerating tissue. This gene-based approach avoids hypertrophic effects on distal organs such as the heart, and eliminates risk of possible neoplasms induced by inappropriate high expression levels of circulating IGF-1. The potential therapeutic role of locally expressed IGF-1 is discussed in the context of current strategies for the attenuation of cardiac cachexia.
authors.affiliation: Mouse Biology Programme, European Molecular Biology Laboratory (EMBL), Monterotondo, Rome, Italy. rosenthal@embl-monterotondo.it
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.forename: Antonio
authors.initials: A
authors.lastname: Musarò
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002100:Cachexia / Q000209:etiology / Q000628:therapy*; D018450:Disease Progression; D015316:Genetic Therapy; D006333:Heart Failure / Q000150:complications / Q000628:therapy*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007334:Insulin-Like Growth Factor I