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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice

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Author(s):
Higuti, Eliza [1] ; Cecchi, Claudia R. [1] ; Oliveira, Nelio A. J. [1] ; Vieira, Daniel P. [1] ; Jensen, Thomas G. [2] ; Jorge, Alexander A. L. [3] ; Bartolini, Paolo [1] ; Peroni, Cibele N. [1]
Total Authors: 8
Affiliation:
[1] Natl Nucl Energy Commiss IPEN CNEN, Dept Biotechnol, Sao Paulo - Brazil
[2] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C - Denmark
[3] Univ Sao Paulo, Sch Med FMUSP, Dept Endocrinol, Genet Endocrinol Unit LIM25, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Review article
Source: CURRENT GENE THERAPY; v. 12, n. 6, p. 437-443, DEC 2012.
Web of Science Citations: 4
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 mu g/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. (AU)

FAPESP's process: 11/21708-6 - Complete phenotypic correction of dwarfism by injection of plasmid DNA in an animal model of isolated growth hormone deficiency
Grantee:Eliza Higuti Sousa
Support Opportunities: Scholarships in Brazil - Doctorate