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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo de Revisão
• Fonte: CURRENT GENE THERAPY; v. 12, n. 6, p. 437-443, DEC 2012.
• Citações Web of Science: 4

Resumo

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)

• Processo FAPESP: 11/21708-6 - Completa correção fenotípica do nanismo mediante injeção de DNA plasmidial em modelo animal de deficiência isolada do hormônio de crescimento
• Beneficiário: Eliza Higuti Sousa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/51848-1 - Utilizacao de vetores lentivirais em modelos animais de terapia genica para o hormonio de crescimento
• Beneficiário: Nélio Alessandro de Jesus Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/51116-0 - Estudo dos efeitos endocrinos e paracrinos na administracao de dna plasmidial em modelos animais de terapia genica
• Beneficiário: Cibele Nunes Peroni
• Modalidade de apoio: Auxílio à Pesquisa - Regular