Efficacy analysis of several drugs in a humanized mouse model of psoriasis

Psoriasis is a highly prevalent disease with great impact on the quality of
life of the patients. Current treatments are far
from ideal. The development of new compounds requires validation in an animal
model, however, many differences
exist between the skin of most animals and humans. TNO Life Sciences has
acquired
expertise in the past year in transplanting human psoriasis skin onto a mouse.
Thereby, we are able to perform
preclinical testing of compounds for psoriasis. Non-laesional skin is
transplanted onto a mouse and after engraftment
injection with autologous T-cells synchronizes the psoriatic process.
Scientific background information can be read in
Appendix 3. Since the study involves pre-clinical testing, patients will not
experience a direct benefit from participation.

In this study, the efficacy of different type drugs, on the development of the
psoriatic process in the humanized mouse model for psoriasis, will be
evaluated. These different, registered drugs intervene at different levels of
the psoriatic process. By comparing these drugs in one study, insight can be
obtained concerning differences in pathways and the sensitivity of different
patients/ biopsies to the different drugs. To gain in depth insight , beside
immunohistochemical evaluation also RNA will be isolated from the biopsies and
analyzed on important gene transcripts that appear to play a role in the
development of psoriasis.
Additionally, effects of the compounds will be evaluated on the immune cells
derived from blood of the patients (in vitro) , this in parallel to the in vivo
mouse study.

.

A pharmaceutical company has asked TNO to test several drugs for psoriasis in
our humanized mouse
model of psoriasis. Besides animal welfare approval, we also need medical
ethical clearance for obtaining skin
biopsies and blood from psoriasis patients. The skin will be transplanted onto
mice after which autologous T-cells
(isolated from the blood of patients) will be injected into the graft to
synchronize development of psoriasis. As indicated
in the study protocol (Appendix 1), 4 skin punch biopsies will be obtained from
non-lesional skin as well as 6 vials of
blood (ca. 10 ml each).

TNO has arranged insurance for the patients participating in this study.
However, medical risks are very low. A week
after obtaining skin and blood samples, the stitches will be removed at the
research center (PT&R) and a check will
take place. With the consent of the patient, the medical practitioner of each
patient will be notified about the
participation.