CONICET | Buscador de Institutos y Recursos Humanos

ABSTRACT The aim of the present article is to discuss the potential of gene therapy for thymic hormonesas a novel therapeutic strategy to treat dyshomeostatic states associated with congenitalathymia or hypofunction of the endocrine thymus. First we will review the advantages of the congenitally athymic (nude) mouse as an animal model to implement experimental thymic hormone gene therapy strategies to restore endocrine thymic function. Recent studies using an adenoviral vector harboring a synthetic gene for the thymic peptide thymulin are reviewed. This adenoviral vector was injected intramuscularly in thymectomized and nude mice as well as in thymectomized rats. Transduced myocytes acted as an ectopic source of thymulin thus restoring circulating thymulin levels to normal levels. This restorative effect was long lasting (several months) even though an adenoviral vector was used. In the rat brain, adenovirallymediated delivery of the synthetic gene for thymulin achieved longer expression than in the case of adenovirally-delivered reporter genes, which is consistent with the reported antiinflammatory activity of thymulin in the brain. Furthemore, neonatal thymulin gene therapy in nude female mice was able to prevent the pituitary and ovarian alterations that typically occur in this mutant after puberty. Neontal thymulin gene therapy in nude mice was able to prevent some of the alterations in lipid metabolism that develop during adult life in these mutants. We conclude that the availability of the above molecular tools should boost basic studies on the molecular biology of thymulin and would also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models and eventually, in humans.