Page 93 - 00. Complete Version - Progress Report IPEN 2014-2016

Biotechnology | Progress Report 93

as co-aged scid mice 15 days after adminis- perfecta, the “oim mice”, after administration
tration in pubertal mice, as well as catch-up of recombinant hGH, obtaining a decrease of
growth increases of the order of 77% for the the fragility and an increase of bone density,
femur length. An example of dissected fe- with consequent decrease in the number of
murs of hGH-DNA-treated mice is shown in fractures, increased weight gain, femur and
Fig.1. A more detailed study comparing DNA animal lengths. Therefore, our main objec-
administration into the quadriceps or tibia- tive is to study, for the first time, the effects of
lis muscle of lit/scid mice under different in- gene therapy by electrotransfer of the mGH
jection conditions (exposed or non-exposed gene in the oim mice, which were already
muscle) and electrotransfer parameters was acquired from The Jackson Laboratories and
also carried out. Our data showed that hGH- are being maintained in our animal facility.
DNA administration into non-exposed tibia- We also can emphasize the continuity of our
lis muscle was an equally efficient, less trau- participation to the most prestigious Inter-
matic treatment, much more suitable for the national Meetings in this area, such as the
pre-clinical testing than injection into ex- 18th Annual Meeting of the American Soci-
posed quadriceps. During this work, a more ety of Gene and Cell Therapy, in New Orle-
precise methodology for femur length de- ans, 2015, in which we participated with one
termination based on initial and final radio- abstract published in the Molecular Therapy.
graphic measurements of the same animal These studies are being carried out in collab-
was set up and these results were accepted oration with the Endocrinology Division of
for publication in Current Molecular Medi- the FMUSP/São Paulo and with the Depart-
cine (Cecchi CR et al., 2017). We are starting ment of Biomedicine at Aarhus University/
a new project in which we intend to use our Denmark. In collaboration with ICB-USP re-
experience with electrotransfer to minimize searchers, the distribution of GH responsive
the effects of osteogenesis imperfecta. This cells was mapped and the receptor involved
is a congenital connective tissue dysplasia, in the central effects of GH was identified. Our
known as brittle bone disease, mainly char- findings deepen the understanding of hGH
acterized by bone deformity, brittleness and signaling in the brain and suggest that central
low density, short stature, and other connec- GH signaling is likely more ample and com-
tive tissue changes associated with structur- plex than formerly recognized and resulted
al or quantitative modifications of collagen. in a publication in Brain Structural Function
The effects of GH have already been reported (Furigo IC et al., 2017).
with an animal model with osteogenesis im-

Figure 1. Dissected right femurs of hGH-DNA-treated and saline-treated lit/scid and of untreated scid mice during a 6-month
bioassay. ls, untreated lit/scid; sc, non-dwarf scid mice; s, saline-treated lit/scid; p, plasmid DNA-treated lit/scid.