Page 92 - 00. Complete Version - Progress Report IPEN 2014-2016

92 Biotechnology | Progress Report

Pituitary Hormones trial decision”, that unfortunately is frequent-

ly independent from the researches. However,
The research and production activities re- an important research line has being carried
lated to the five human pituitary hormones, out developing alternative ex vivo and in vivo
namely growth hormone (hGH), prolactin Gene Therapy strategies for phenotypic cor-
(hPRL), thyrotropin (hTSH), follitropin (hFSH) rection of dwarfism, using the human (hGH)
and luteotropin (hLH), still constitute the ba- and the mouse (mGH) genes. In these stud-
sic working field of the group. Our goal is the ies, two animal models available at our an-
development of applied research, especial- imal facility, the immunocompetent dwarf
ly emphasizing the interaction between the (lit/lit) and the immunodeficient dwarf (lit/
Academic and the Industrial worlds, an as- scid) mice, are employed. The goal of this ap-
pect that has been neglected for so long in proach is the development of an animal mod-
Brazil. Under this aspect, a partnership with el, based on these dwarf mice, in which it can
the company Biosynthesis has been started in 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 research-
and with clinicians from FMUSP, especially in es are thus moving closer to pre-clinical test-
the field of Gene Therapy, with the groups of ing. More recently, the efforts were concen-
Genetic Ichthyology and the Faculty of Phar- trated on the use of an in vivo system based
maceutical Sciences of USP for the purpose on naked hGH DNA administration followed
of cloning Arapaima gigas (Pirarucu) gonad- by electroporation in the quadriceps muscle
otropins, and with the Department of Phys- of lit/scid mice. In a previous work, we relat-
iology and Biophysics of the Institute of Bio- ed a sustained secretion of hGH during a 60-
medical Sciences (ICB/USP) for studies related day assay together with a highly significant
to prolactin and growth hormone. As always, increase in the body weight of these animals.
the main emphasis of the group has been giv- In this period, we also developed a novel ho-
en to scientific production and to collabora- mologous model, in which the mGH gene
tion with well-known national and interna- was electrotransfered to the immunocom-
tional research groups. Thus, in this 3-year petent mice (lit/lit), a condition more similar
period, 16 scientific papers have been pub- to that of GH-deficient children (Cecchi CR et
lished all in international journal whose im- al., 2014). The results of this work also con-
pact factor was always between 1 and 6.4, firmed the feasibility of the proposed treat-
and 2 Meeting Abstracts published in jour- ment, both in terms of higher circulatory lev-
nals of high impact. els of the main effector of GH, the insulin-like
growth factor I (IGF-I), and the absence of an-
Human growth ti-GH antibody formation. In a recent work
hormone (hGH) (Higuti E et al., 2016), we set up a more effec-
tive pre-clinical assay in pubertal dwarf (lit/
scid) mice treating 40-day old animals inject-
Human growth hormone (hGH) production ed with hGH-DNA into the non-exposed tib-
and quality control has been already estab- ialis cranialis muscle, via a less invasive ap-
lished at the laboratory level and, as stated proach. This treatment provided, for the first
several times, is only waiting for the “indus- time, IGF-I concentrations at the same level

Instituto de Pesquisas Energéticas e Nucleares