| ARVID CARLSSON'S COLUMN
Arvid Carlsson comments the
latest research on transplantation studies of
patients with Parkinson's disease. His conclusion
is that such transplantations cannot possibly
succeed. The reason is that the new cells cannot
replace the old cells in important feedback
systems of the brain. Transplantations will cause
sustained adverse side effects rather than
improve the symptoms.
Placebo-controlled
studies do not support transplantation
Transplantation to the brain in Parkinson's
disease has no future. They are foredoomed to
failure. This view is supported by the latest
years' research. According to this research,
there is a strong placebo effect, and side
effects of the muscle function are common, after
these operations. These results are not
surprising, considering our brain's way of
functioning. If stem cells instead of fetal cells
come into use the problems will probably get
worse.
Since the nineteen-eighties, Swedish scientists
have done pioneer work by initiating trials with
transplantation in Parkinson's disease, at first
in animals and then in patients. In the
experiments in patients dopamine producing fetal
cells have been used. The preliminary results
from these studies were promising. But the
studies were not placebo-controlled, and later on
the picture has changed.
Two placebo-controlled trials were done in the
US. The patients received transplants of human
dopamine producing fetal cells. The results are
generally in goood correspondence and can be
summarized in the following way:
When comparing the transplanted patients with the
placebo-treated patients, hardly any significant
difference in movement function was observed.
(The patients then did not get any dopamine
substitute.) Another obvious difference was
however noticed between the two groups: Several
of the transplanted patients developed
dyskinesias, that is involuntary movements, even
in the absence of medicine. In none of the
studies were further clinical trials of
transplantation recommended, at the present stage
of research.
Ingenious feedback
system
This is not the first time that open-labeled
studies have not been confirmed by
placebo-controlled studies. This result is really
not surprising bearing in mind our current
knowledge. The dopamine plays an extremely
important role in making our muscular movements
as fast, smooth and effective as possible. In
order to make this possible, the
dopamine-producing neurons are connected in an
ingenious control system, where many different
nerve cells take part in complicated neural
circuits. When the dopamine neurons die in
Parkinson's disease, there is a gap in the
system. Is it reasonable to assume that
transplanted dopamine cells could fill this gap
and thereby replace the lost cells? In my opinion
the answer is no. To explain my point of view,
let me use a simple metaphor.
The dopamine-producing nerve cells are part of a
chain of nerve cells. This means that, on one
hand, the dopamine cells are controlled by
certain cells, while, on the other hand, the
dopamine cells themselves control other cells.
This can be compared to a horse and carriage. The
dopamine cells are the horse, and the cells that
control the dopamine cells are the driver. The
cells which are steered by the dopamine are the
wagon. In order to function, the transplanted
cells must be incorporated as a horse between the
driver and the wagon. But here a great problem
instantly arises. In most cases the dopamine
cells have been transplanted to the corpus
striatum. The dopamine cells that were lost in
Parkinson's disease were situated far away,
namely in "the black nucleus". This is
where the driver is (or at least his reins). So
the transplanted cells are out of reach of the
driver. The expected consequences are that the
transplanted dopamine cells cannot contribute to
any suitable muscle function, but rather to
uncontrolled, purposeless movements, that is
dyskinesias. So the results reported above were
foreseeable.
Would it not be possible then to perform the
transplantations into the black nucleus instead?
Well, such attempts have been made. But then
another problem arises: Certainly, the driver and
the horse are now close to each other, and maybe
they could be connected in a purposeful way
(though as a matter of fact this is not evident).
But the horse is now out of reach of the wagon,
which is far away, in corpus striatum.
Stem cells are no
solution
Scientists in this area hope to resolve the
problems by culturing stem cells, to get a
greater supply of dopamine producing nerve cells.
But the stumbling-block is not at all the supply
of cells. As a matter of fact the transplanted
fetal cells have demonstrated good survival. And
these cells produce efficient quantities of
dopamine, as is evident from the dyskinesias.
Therefore, if the amount of transplant is
increased, one can expect greater effects of the
same kind as before, that is more dyskinesias in
the first place.
June 2006
Arvid Carlsson
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