title: Growth responses following a single intra-muscular hGH plasmid administration compared to daily injections of hGH in dwarf mice.
abstract: In previous work, sustained levels of circulating human growth hormone (hGH) and a highly significant weight increase were observed after electrotransfer of naked plasmid DNA (hGH-DNA) into the muscle of immunodeficient dwarf mice (lit/scid). In the present study, the efficacy of this in vivo gene therapy strategy is compared to daily injections (5 μg/twice a day) of recombinant hGH (r-hGH) protein, as assessed on the basis of several growth parameters. The slopes of the two growth curves were found to be similar (P > 0.05): 0.095 g/mouse/d for protein and 0.094 g/mouse/d for DNA injection. In contrast, the weight increases averaged 35.5% (P < 0.001) and 23.1% (P < 0.01) for protein and DNA administration, respectively, a difference possibly related to the electroporation methodology. The nose-to-tail linear growth increases were 15% and 9.6% for the protein and DNA treatments, respectively, but mouse insulin-like growth factor I (mIGF-I) showed a greater increase over the control with DNA (5- to 7-fold) than with protein (3- to 4-fold) administration. The weight increases of several organs and tissues (kidneys, spleen, liver, heart, quadriceps and gastrocnemius muscles) were 1.3- to 4.6-fold greater for protein than for DNA administration, which gave a generally more proportional growth. Glucose levels were apparently unaffected, suggesting the absence of effects on glucose tolerance. A gene transfer strategy based on a single hGH-DNA administration thus appears to be comparable to repeated hormone injections for promoting growth and may represent a feasible alternative for the treatment of growth hormone deficiency.
authors.affiliation: Biotechnology Department, National Nuclear Energy Commission (IPEN-CNEN), Cidade Universitaria, São Paulo, SP, Brazil.
authors.forename: Eliza
authors.initials: E
authors.lastname: Higuti
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Cecchi
authors.forename: Nelio A J
authors.initials: NA
authors.lastname: Oliveira
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Vieira
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Jensen
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
authors.forename: Paolo
authors.initials: P
authors.lastname: Bartolini
authors.forename: Cibele N
authors.initials: CN
authors.lastname: Peroni
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004392:Dwarfism / Q000188:drug therapy / Q000378:metabolism; D018274:Electroporation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006321:Heart / Q000187:drug effects / Q000254:growth & development*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000254:growth & development*; D008099:Liver / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009929:Organ Size; D010957:Plasmids / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000254:growth & development; D013997:Time Factors; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I