| There
are four signs that indicate the possibility that a patient
may have Parkinson's Disease (PD):
1. Tremors, which have a fixed
frequency, (although these can of course be caused by other
conditions).
2. Rigidity i.e. stiffness of the muscle.
3. Akinesia i.e. difficulty in moving.
4. Postural problems - i.e. difficulty in walking etc.
In spite of very extensive
research all around the world, not much is known as to what
causes these symptoms, although we do know where the problem
lies in the brain. There is evidence of degeneration of one
part of the brain, the substantia nigra, which projects to
the basal ganglia and cortex. This pathway utilises a substance
called dopamine. The lack of this particular chemical causes
PD.
Understanding the cause/nature
of the disease
Degeneration of the substantia
nigra at the base of the brain occurs in other diseases, but
in Parkinson's disease the affected nerve cells contain characteristic
accumulations of altered proteins. These neuronal inclusions
are known as Lewy bodies. Our work on motor neurone disease
and Parkinson's disease coincides because we are studying
neurofilament proteins which are known to accumulate in the
affected nerve cells both in Parkinson's disease and motor
neurone disease.
Understanding the biology
of neurofilaments, identifying mutations in the genes responsible
for making neurofilaments, and investigating how toxins affect
neurofilaments, is helping us to understand the process of
nerve cell death. A further link with motor neurone disease
turns upon free radicals, which have been implicated in Parkinson's
disease. Our biochemical and molecular studies in both these
conditions will help us to define how free radicals could
lead to nerve cell damage, and will lead to new strategies
for preventing the death of these vulnerable cells.
What do we actually know about
the chemical side of things? These are areas we have been
looking at in detail. Dopamine acts on dopamine receptors.
We now know that there are five types of these receptors in
the brain. The main area that we are concerned with is the
area called the striatum, made up of the caudate, nucleus
and the putamen. Dysfunction in this area leads to the manifestation
of the disease - such as akinesia, difficulty in writing and
walking. It is also possible to see how many other areas of
the brain are involved. The more we understand the disease
the more we can recognise that there are areas in the brain
that were previously thought not to be affected, that we now
know are affected. The drugs that are working on the two main
dopamine receptors, D1 and D2 receptors, are also working
on other areas as well. Consequently when one treats Parkinson's
disease for a long time complications develop.
Apart from the clinical signs,
we do not have a test that shows whether someone has Parkinson's
disease or not. A PET scan might be of some help but only
Hammersmith Hospital in London carries out PET scans for Parkinson's
disease.
If a patient is given the
chemical Fluoro-dopa-glucose the caudate and putamen cells
"light up" in normal patients. In those with Parkinson's
disease the caudate still lights up but there is hardly any
putamen activity. However, this is not straightforward because
(a) it is a very expensive technique, (b) it has limited availability
and (c) the result is not always accurate. In some patients
it will tell us what is going on but in others itmay not.
However, we are developing a method of diagnosing Parkinson's
disease by a simpler method using an MRI scanner and a technique
called MR spectroscopy (MRS).
Much effort has been put into
improving the treatment of Parkinson's disease. One of the
new treatments is apomorphine, which is given by injection.
The department at the Institute of Psychiatry & King's
College Hospital is a major centre for apomorphine use. This
treatment is very similar to that for diabetes in that in
diabetes there is lack of insulin and in Parkinson's disease
there is a lack of dopamine. It seems reasonable to supplement
the dopamine by injection.
Another treatment is surgery
and the PD Clinic has carried out its first pallidotomy operation
which involves making a sterotactic lesion in the palladium.
Another surgical method is
similar to carrying out a pacemaker implantation in the heart.
This will involve placing a small pacemaker in the part of
the brain, which is affect by Parkinson's disease, namely
the thalamus or subthalamic nucleus. The patient will have
a small switch on the skin surface which they can operate
whenever they want to. This technique has been shown to cause
dramatic improvement of tremor.
The Institute Parkinson's
disease clinic, is hoping to establish surgical treatment
for Parkinson's disease as a readily available procedure for
selected patients. Furthermore, it is also hoping to validate
the use of MRS in the diagnosis of Parkinson's disease where
clinical signs are unclear.
What the Institute is
doing:
Demonstrating that Parkinson's
disease in people of Afro-Caribbean descent is clinically
different from Parkinson's in caucasian people.
Improving the treatment of
Parkinson's disease using new surgical treatments such as
palidotomy and the implantation of stimulators into the subthalamic
nucleus of the brain.
Developing a new methodology
for studying the neuroprotective effect of drugs such as Riluzole
in the Parkinsonian syndromes progressive supranuclear palsy
and multiple system atrophy. |
