Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease.
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-[(18)F]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.
Brundin
P
P
Section for Neuronal Survival, Division of Neurobiology, Department of Physiological Sciences, Lund University, Sweden.
Pogarell
O
O
Hagell
P
P
Piccini
P
P
Widner
H
H
Schrag
A
A
Kupsch
A
A
Crabb
L
L
Odin
P
P
Gustavii
B
B
Björklund
A
A
Brooks
D J
DJ
Marsden
C D
CD
Oertel
W H
WH
Quinn
N P
NP
Rehncrona
S
S
Lindvall
O
O
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000502:physiology / Q000601:surgery*; D004298:Dopamine / Q000502:physiology; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000637:transplantation*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy / Q000628:therapy*; D011281:Pregnatrienes / Q000009:adverse effects / Q000627:therapeutic use*; D011699:Putamen / Q000000981:diagnostic imaging / Q000502:physiology / Q000601:surgery*; D014055:Tomography, Emission-Computed
D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D011281:Pregnatrienes; D007980:Levodopa; D004298:Dopamine; C053355:tirilazad