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


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