| Animal models for CNS disorders have
been shown to have limited predictive
power for man, which in many cases is due
to weaknesses in the animal models
themselves. However, these models can
often provide the information which is key
to ensuring efficacy throughout formal
preclinical development and Phase I
clinical trials.
So, how can the investigator
weigh up the strengths and weaknesses of
different models in order for them to be
used effectively so as to ensure that
efficacy seen in animal studies translates
into the clinic? This article will discuss the
issues in relation to stroke, where a number
of promising therapies have failed in the
clinic, identifies broader relevance to other
CNS conditions, and considers how to
ensure that animal models enhance the
prediction of efficacy in patients (1).
DEVELOPMENT OF THERAPIES
FOR STROKE
Stroke is described as the rapid loss of
brain function due to damage or a blockage
of the blood vessels supplying blood to the
brain, and can be due to a haemorrhage
or ischaemia caused by thrombosis or
embolism. Whilst these mechanisms all
involve disruption of the blood supply to the
brain, the range of mechanisms leading to
disruption of blood flow and the extent of
damage offers a range of potential
therapeutic interventions, whilst making
selection of the appropriate preclinical
models more difficult (see Figures 2-4). |
