Page 4 - PR 2014 2016 04 Biotechnology
P. 4
90 Biotechnology | Progress Report
Pituitary Hormones “industrial decision”, that unfortunately is
frequently independent from the research-
The research and production activities related es. However, an important research line has
to the five human pituitary hormones, name- being carried out developing alternative ex
ly growth hormone (hGH), prolactin (hPRL), vivo and in vivo Gene Therapy strategies for
thyrotropin (hTSH), follitropin (hFSH) and phenotypic correction of dwarfism, using the
luteotropin (hLH), still constitute the basic human (hGH) and the mouse (mGH) genes. In
working field of the group. Our goal is the these studies, two animal models available
development of applied research, especially at our animal facility, the immunocompetent
emphasizing the interaction between the dwarf (lit/lit) and the immunodeficient dwarf
Academic and the Industrial worlds, an aspect (lit/scid) mice, are employed. The goal of this
that has been neglected for so long in Brazil. approach is the development of an animal
Under this aspect, a partnership with the model, based on these dwarf mice, in which it
company Biosynthesis has been started in can be possible to obtain useful and sustained
that period generating an important project circulatory levels of growth hormone with
PIPE-FAPESP. We continued our main collabo- phenotypic corrections, such as body weight
rations with the Aarhus University (Denmark) gain and longitudinal growth. Our researches
and with clinicians from FMUSP, especially are thus moving closer to pre-clinical testing.
in the field of Gene Therapy, with the groups More recently, the efforts were concentrated
of Genetic Ichthyology and the Faculty of on the use of an in vivo system based on
Pharmaceutical Sciences of USP for the pur- naked hGH DNA administration followed by
pose of cloning Arapaima gigas (Pirarucu) electroporation in the quadriceps muscle of
gonadotropins, and with the Department of lit/scid mice. In a previous work, we related
Physiology and Biophysics of the Institute a sustained secretion of hGH during a 60-
of Biomedical Sciences (ICB/USP) for studies day assay together with a highly significant
related to prolactin and growth hormone. increase in the body weight of these animals.
As always, the main emphasis of the group In this period, we also developed a novel ho-
has been given to scientific production and mologous model, in which the mGH gene
to collaboration with well-known national was electrotransfered to the immunocompe-
and international research groups. Thus, in tent mice (lit/lit), a condition more similar to
this 3-year period, 16 scientific papers have that of GH-deficient children (Cecchi CR et al.,
been published all in international journal 2014). The results of this work also confirmed
whose impact factor was always between 1 the feasibility of the proposed treatment, both
and 6.4, and 2 Meeting Abstracts published in terms of higher circulatory levels of the
in journals of high impact. main effector of GH, the insulin-like growth
factor I (IGF-I), and the absence of anti-GH
Human growth antibody formation. In a recent work (Higu-
hormone (hGH) ti E et al., 2016), we set up a more effective
pre-clinical assay in pubertal dwarf (lit/scid)
mice treating 40-day old animals injected
Human growth hormone (hGH) produc- with hGH-DNA into the non-exposed tibialis
tion and quality control has been already cranialis muscle, via a less invasive approach.
established at the laboratory level and, as This treatment provided, for the first time,
stated several times, is only waiting for the IGF-I concentrations at the same level as co-
Instituto de Pesquisas Energéticas e Nucleares
