Simulation of dementia by induction og global cerebral deficit syndrome (normobaric hypoxia)
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Usefulness of the methods
The potential of a drug to improve the symptoms of
dementia by induction of global cerebral deficit syndrome (cerebral deficit)
has to be proven in patients. However, with multi-morbid patients showing different
spontaneous courses of their illness, fixing the effective dose range, tracing
the optimum dose and obtaining knowledge of the time-effect relationship of
new drugs before starting the main clinical trials, is difficult, time consuming
and costly. These data are indispensable for a good clinical development programme.
Using simulation of dementia in volunteers (induction
of a global cerebral deficit syndrome) - as a system for drug testing early
in the clinical development of an investigational drug - can provide this information
at low cost in a very short time. Moreover, obtaining proof of concept data
early may make considerable savings. Our methods can be run in parallel with
the preparation of the clinical studies to allow the feedback influence of our
results to be incorporated. Our sensitive and predictive model has proven to
be very suitable for this purpose.
Principle of the methods
Induction of hypoxia as a model of dementia:
Volunteers inhale air with a reduced content of oxygen (10 % O2, 90 % N2).This
results in a global functional cerebral deficit characterised by a decrease
in vigilance and CNS performance similar to that observed in clinical dementia.
These changes can be optimally measured with our test battery. Similar to human
dementia are also humoral changes which we find during hypoxia (e.g. increase
in the blood concentrations of growth hormone, adrenaline and noradrenaline).
In animal experiments hypoxia can be shown to reduce acetylcholine synthesis,
decrease the incorporation of glucose into alanine aspartate, GABA, glutamate
and serine and to diminish glycolysis and the content of relevant substrates
as ATP in the brain.
Measurements:
The system of multidimensional tests measuring the deficits in vigilance and
performance (presented in detail on the back of this page) is designed to be
comprehensive enough to assess the multitude of cerebral dysfunctions which
are usually found in patients suffering from dementia of different causes.
Advantages of the methods
Low interindividual variation due to:
Reference data
Data pools are available for different kinds of encephalotropic drugs and for antidepressants of the newer generation.
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