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Brain, Vol. 123, No. 7, 1380-1390, July 2000
© 2000 Oxford University Press

Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease

.

Patrik Brundin5,6, Oliver Pogarell9,10, Peter Hagell1,2, Paola Piccini8, Håkan Widner2,5,6, Anette Schrag7, Andreas Kupsch9, Lesley Crabb7, Per Odin1,2, Björn Gustavii4, Anders Björklund6, David J. Brooks8, C. David Marsden{dagger},7, Wolfgang H. Oertel9,10, Niall P. Quinn7, Stig Rehncrona3 and Olle Lindvall1,2

1 Section of Restorative Neurology, 2 Division of Neurology and 3 Division of Neurosurgery, Department of Clinical Neuroscience and 4 Department of Obstetrics and Gynaecology, University Hospital and 5 Section for Neuronal Survival, 6 Division of Neurobiology, Department of Physiological Sciences, Lund University, Lund, Sweden, 7 University Department of Clinical Neurology, the National Hospital for Neurology and Neurosurgery, 8 MRC Cyclotron Unit, Hammersmith Hospital, London, UK, 9 Department of Neurology, Klinikum Grosshaden, Munich and 10 Department of Neurology, Center of Nervous Diseases, Philipps-University Marburg, Marburg, Germany

Correspondence to: Olle Lindvall, Section of Restorative Neurology, Division of Neurology, Department of Clinical Neuroscience, University Hospital S-221 85 Lund, Sweden E-mail: Olle.Lindvall{at}neurol.lu.se

Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in `off' phase was reduced by a mean of 40%. At 10–23 months after grafting, PET showed a mean 61% increase of 6-L-[18F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.


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