Page 5 - PR 2014 2016 04 Biotechnology

Biotechnology | Progress Report 91

aged scid mice 15 days after administration mice”, after administration of recombinant
in pubertal mice, as well as catch-up growth hGH, obtaining a decrease of the fragility
increases of the order of 77% for the femur and an increase of bone density, with con-
length. An example of dissected femurs of sequent decrease in the number of fractures,
hGH-DNA-treated mice is shown in Fig.1. A increased weight gain, femur and animal
more detailed study comparing DNA admin- lengths. Therefore, our main objective is to
istration into the quadriceps or tibialis muscle study, for the first time, the effects of gene
of lit/scid mice under different injection con- therapy by electrotransfer of the mGH gene
ditions (exposed or non-exposed muscle) and in the oim mice, which were already acquired
electrotransfer parameters was also carried from The Jackson Laboratories and are being
out. Our data showed that hGH-DNA admin- maintained in our animal facility. We also
istration into non-exposed tibialis muscle was can emphasize the continuity of our partici-
an equally efficient, less traumatic treatment, pation to the most prestigious International
much more suitable for the pre-clinical test- Meetings in this area, such as the 18th Annual
ing than injection into exposed quadriceps. Meeting of the American Society of Gene and
During this work, a more precise methodol- Cell Therapy, in New Orleans, 2015, in which
ogy for femur length determination based we participated with one abstract published
on initial and final radiographic measure- in the Molecular Therapy. These studies are
ments of the same animal was set up and being carried out in collaboration with the En-
these results were accepted for publication docrinology Division of the FMUSP/São Paulo
in Current Molecular Medicine (Cecchi CR and with the Department of Biomedicine at
et al., 2017). We are starting a new project Aarhus University/Denmark. In collaboration
in which we intend to use our experience with ICB-USP researchers, the distribution
with electrotransfer to minimize the effects of of GH responsive cells was mapped and the
osteogenesis imperfecta. This is a congenital receptor involved in the central effects of GH
connective tissue dysplasia, known as brittle was identified. Our findings deepen the un-
bone disease, mainly characterized by bone derstanding of hGH signaling in the brain
deformity, brittleness and low density, short and suggest that central GH signaling is likely
stature, and other connective tissue changes more ample and complex than formerly rec-
associated with structural or quantitative ognized and resulted in a publication in Brain
modifications of collagen. The effects of GH Structural Function (Furigo IC et al., 2017).
have already been reported with an animal
model with osteogenesis imperfecta, the “oim

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.