Biology Reference
In-Depth Information
locomotor outcome data. In contrast, patients in the respective clinical trial
received the treatment with a mean treatment delay of 52.6 h after injury
(
Fehlings et al., 2011
).
1.5. Requirements for appropriate preclinical data acquisition
Based on this review of four “bed to bedside” treatment strategies, the fol-
lowing question arises: How can we improve preclinical research in order to
increase the likelihood that translation into the clinic will become successful?
Several reviews (
Anderson, Beattie, Blesch, et al., 2005; Blesch &Tuszynski,
2009
) and a recently published survey among the SCI research community
(
Kwon, Hillyer, & Tetzlaff, 2010
) identified prerequisites which preclinical
research should fulfill before respective therapeutic strategies can be applied
to the clinical setting.
Overall, both reviews and the survey come to similar conclusions. Effi-
cacy of a pharmacological and in particular a cell-based intervention should
be assessed not only in rodent models of SCI but also in large animal models
(e.g., cats, dogs, rabbits, sheep). According to the survey, primate experi-
ments are not considered as crucial. Contusion SCI is the most relevant an-
imal model to mimic human SCI pathology and should therefore be
employed in preclinical studies prior to translation. Moreover, a given ther-
apy should be investigated in different injury models as well as different
injury severities to document the robustness of a given approach. In the sur-
vey, the majority of respondents felt that morphological, biochemical, or
neurophysiologic outcome parameters are not sufficient to replace behav-
ioral tests, since they do not represent functionally meaningful outcome
parameters. According to the survey, locomotor assessment-in particular,
the frequently employed semiquantitative analysis (BBB locomotor rating
scale)-is still considered to represent “clinically meaningful efficacy” best
(
Kwon et al., 2010
). In terms of treatment timing, a therapy with the inten-
tion to be applied within 12 h after SCI injury in humans should be inves-
tigated with a minimum treatment delay of 6 h in the preclinical setting. If
the treatment delay in humans is longer (e.g., 5 days), corresponding delays
need to be investigated preclinically (
Anderson et al., 2005; Kwon et al.,
2010
). Finally, there is strong consensus that evidence of efficacy from a
single laboratory is not sufficient. Respective experiments need to be
replicated by other independent laboratories.
How did the approaches discussed here perform in this respect
(
Table 7.3
)? None of the studies reported a large animal model (pig, sheep,
