Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease.
Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.
Lindvall
O
O
Department of Neurology, University of Lund, Sweden.
Sawle
G
G
Widner
H
H
Rothwell
J C
JC
Björklund
A
A
Brooks
D
D
Brundin
P
P
Frackowiak
R
R
Marsden
C D
CD
Odin
P
P
D016380:Brain Tissue Transplantation; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004298:Dopamine; D016332:Fetal Tissue Transplantation; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008636:Mesencephalon / Q000196:embryology / Q000637:transplantation*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery*; D011699:Putamen / Q000378:metabolism / Q000601:surgery*
C043437:fluorodopa F 18; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D004298:Dopamine