EVIDENCE FOR LONG-TERM SURVIVAL AND FUNCTION OF DOPAMINERGIC GRAFTS IN PROGRESSIVE PARKINSONS-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 embryo nic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant a melioration of parkinsonian symptoms and increased 6-L-[F-18]-fluorodo pa uptake in the grafted putamen, as assessed with positron emission t omography. Three years after grafting the patients still exhibited inc reased fluorodopa uptake in the grafted putamen and significant clinic al improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the ''off'' phase, and by a prolongation of t he effect of a single dose of L-dopa Between 2 and 3 years after surge ry, Patient 3 showed only minor changes of parkinsonian symptoms on th e side contralateral to the graft, whereas there was a worsening on th e ipsilateral side. Fluorodopa uptake decreased in the nongrafted puta men but was unchanged in the grafted putamen. Patient 4 continued to i mprove after the first postoperative year and L-dopa was withdrawn aft er 32 months. The reduction of parkinsonian symptoms on the side contr alateral to the graft became more pronounced between 1 and 3 years aft er surgery. Fluorodopa uptake further increased in the grafted putamen , whereas no change was detected on the nongrafted 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.