178. Early Treatment for Growth Hormone Deficiency Based on Naked DNA Administration in Dwarf Mice Allows Efficient Catch-Up Growth

Abstract

and injected with lipase inhibitor, further verifying that this genetic approach markedly diminished hepatic lipid synthesis. In BAT, Fgf21 transfer induced a "super-brown" phenotypic change, which was accompanied by elevated expression of a panel of vital genes for adaptive thermogenesis, such as Ucp1, Pgc1-alpha, Cidea, Dio2 and Elovl3. Collectively, our findings unveil that the triglyceride-lowering effect of cold exposure can be fully recapitulated by liver-specific delivery of the Fgf21 using a hydrodynamics-based procedure, indicating that this new approach may provide an alternative and more acceptable option for hyperlipidemia therapy in humans.

Potentialities of Gene Therapy in Pediatric Endocrinology

“…Besides skeletal muscle cells, other genetically modified cell types have been used as GH delivery devices in animal models, such as fibroblasts [51, 52], bone marrow stromal cells [53], and salivary glands [54]. Recently, Higuti et al [55] investigated a gene therapy approach based on the injection, in young and old lit/scid dwarf mice, of a plasmid in tibialis cranialis muscle encoding the hGH under the control of ubiquitin C promoter, followed by electrotransfer. Treatment resulted effective in promoting the catch-up growth and mIGF-I secretion, especially in young dwarf mice, which normalized IGF-I plasma levels 15 days after GT [55].…”

“…Recently, Higuti et al [55] investigated a gene therapy approach based on the injection, in young and old lit/scid dwarf mice, of a plasmid in tibialis cranialis muscle encoding the hGH under the control of ubiquitin C promoter, followed by electrotransfer. Treatment resulted effective in promoting the catch-up growth and mIGF-I secretion, especially in young dwarf mice, which normalized IGF-I plasma levels 15 days after GT [55].…”