Growth responses following a single intra-muscular hGH plasmid administration compared to daily injections of hGH in dwarf mice

Eliza Higuti, Cláudia R. Cecchi, Nélio A. Oliveira, Daniel P. Vieira, Thomas G. Jensen, Alexander A.L. Jorge, Paolo Bartolini, Cibele N. Peroni

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)437-443
Number of pages7
JournalCurrent gene therapy
Volume12
Issue number6
DOIs
StatePublished - Dec 3 2012

Keywords

  • Electroporation
  • Gene therapy
  • Human growth hormone
  • Immunodeficient little mice
  • Mouse insulin-like growth factor I
  • Naked DNA

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