LENA CARLSSON'S COLUMN
Overview of the latest research in
transplantation in patients with Parkinson's
disease.
Background
Parkinson's disease is an
illness which affects around one percent of the
people above 50 years of age. Parkinson's disease
is characterized by tremor and rigidity of the
muscles, and difficulties in movement. These
symptoms are caused by the death of neurons that
produce dopamine in the substantia nigra (the
black nucleus) in the lower part of the brain
stem. The fibers of the dopamine cells lead to
the striatum, which controls the movements of the
muscles. The striatum is situated in the central
parts of the brain. The death of the dopamine
cells in the black nucleus results in a
deficiency of dopamine in the striatum. As a
consequence, the muscular movements can no longer
be correctly controlled.
Parkinson's disease is treated by l-dopa and
other drugs which increase the amount of dopamine
in the brain. The medicines however have a good
effect mostly in the beginning. Therefore other
treatments are wanted. Since 1987 trials have
been made with transplantations of
dopamine-producing fetal cells on about 350
patients. These trials have given much varying
results, and therefore many people hope that stem
cells can instead be used. Stem cells, which can
be found in the embryo among other places,
sometimes have the capability to differentiate
into neurons. Transplantation in Parkinson's
disease is still at an experimental stage.
Overview
Two studies of
transplantation in Parkinson's disease with
partly new technology were published in 2005. The
patients improved and no patient developed
so-called dyskinesia, which is otherwise often a
great problem in similar transplantations.
In one study cells from the retina were
transplanted instead of fetal cells. In the other
study the patients received fetal cells in
suspension. These cells were selected neurons
which are especially liable to degenerate and die
in Parkinson's disease. Moreover, in this other
study the cells for the first time were also
transplanted to the substantia nigra (the black
nucelus), in addition to the striatum.
Just like these two investigations, most earlier
studies have been open-label studies, which means
that no control groups have been used. Therefore,
NIH (the National Institutes of Health) initiated
two placebo-controlled investigations in the US a
couple of years ago. The follow-up of one of
these studies suggests that the placebo effect in
transplantation can be very strong. This is true
of both objective and subjective measures of
muscular function. Those patients who believed
they were transplanted, improved more than those
patients who believed they underwent sham
surgery.
The American scientists Warren Olanow and Brian
Snyder have gone through studies of
transplantation and research on stem cells in a
review article in 2005. In this article the
authors are more optimistic than Olanow was in
2004, when he did not want to recommend
transplantation in Parkinson's disease. The
authors believe that the results from the
transplantation trials can be improved upon, and
that stem cells offer great promise as a therapy
for Parkinson's disease. Numerous problems must
however first be overcome. The authors also think
that unrealistic expectations have been created
regarding stem cells.
Olle Lindvall and Anders Björklund at the
University of Lund, Sweden, have also done
research in transplantation. In a review article
in 2004 they establish that the results from
transplantations with fetal cells are varying.
The authors find it unlikey that such
transplantations will become routine treatment in
Parkinson's disease. Just like Olanow and Snyder
they look upon stem cells as an alternative in
the long term.
References
Stover NP, Bakay RA,
Subramanian T, Raiser CD, Cornfeldt ML,
Schweikert AW, Allen RC, Watts R: Intrastriatal
implantation of human retinal pigment epithelial
cells attached to microcarriers in advanced
Parkinson disease. Arch Neurol. 2005
Dec;62(12):1833-7
Ivar Mendez et al: Cell type analysis of
functional fetal dopamine cell suspension
transplants in the striatum and substantia nigra
of patients with Parkinson's disease. Brain 2005
128(7): 1498-1510
Olanow CW, Goetz CG, Kordower JH et al. A
double-blind controlled trial of bilateral fetal
nigral transplantation in
Parkinson's disease. Ann Neurol 2003; 54(3):
403-14
Snyder Brian, Olanow CW: Stem cell treatment for
Parkinson's disease: an update for 2005. Curr
Opin Neurol. 2005 Aug;18(4):376-85
Lindvall Olle, Björklund Anders. Cell Therapy in
Parkinson's Disease. NeuroRx 2004 Oct;1(4):
382-392
Freed CR, Greene PE, Breeze RE, Tsai WY,
DuMouchel W, Kao R, Dillon S, Winfield H, Culver
S, Trojanowski JQ, Eidelberg D, Fahn S.
Transplantation of embryonic dopamine neurons for
severe Parkinson's disease. N Engl J Med. 2001
Mar 8;344(10):710-9
Gordon PH, YU Q, Qualis C et al. Reaction time
and movement time after embryonic cell
implantation in Parkinson's disease.
Arch Neurol 2004; 61(6): 858-61
McRae C, Cherin E, Yamazaki TG et al. Effects of
perceived treatment on quality of life and
medical outcomes in a double-
blind placebo surgery trial. Arch Gen Psychiatry
2004; 61(4): 412-20
june 2006
Lena Carlsson
© Lena Carlsson
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