Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study. Report of three cases.
The main neural transplantation strategy in Parkinson disease (PD) has been focused on reinnervating the striatum. The clinical results reported in patients who receive transplants have been limited and do not justify the use of neural transplantation as a routine therapeutic procedure for PD. Identifying the optimal target for transplantation may be one of the critical factors for optimizing clinical outcomes. Evidence from preclinical studies indicates that simultaneous intrastriatal and intranigral grafts (double grafts) may produce a more complete functional recovery. The authors report the clinical and positron emission tomography (PET) scanning results in three patients enrolled in a safety and feasibility pilot study who received double grafts and who have been followed for up to 13 months posttransplantation. Patients included in the study had idiopathic PD. All patients underwent detailed assessments before and after surgery, in accordance with the Core Assessment Program for Intracerebral Transplantation. The patients received implants of fetal mesencephalic cell suspensions in the putamen and substantia nigra (SN) bilaterally. There were no intraoperative or perioperative complications. Follow-up PET scans demonstrated an increase in the mean fluorodopa uptake constant values in the putamen and SN 12 months postsurgery. Improvements were also noted in the total Unified Parkinson's Disease Rating Scale, Hoehn and Yahr, Schwab and England, and pronation/supination scores after transplantation. The authors demonstrate the feasibility of reinnervating the SN and striatum by using a double transplant strategy in humans.
Mendez
Ivar
I
Department of Surgery (Neurosurgery), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada. mendez@is.dal.ca
Dagher
Alain
A
Hong
Murray
M
Gaudet
Paula
P
Weerasinghe
Swarna
S
McAlister
Vivian
V
King
David
D
Desrosiers
Jacques
J
Darvesh
Sultan
S
Acorn
Tanya
T
Robertson
Harold
H
D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004292:Dominance, Cerebral / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D016332:Fetal Tissue Transplantation; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000637:transplantation*; D008875:Middle Aged; D009460:Neurologic Examination; D009474:Neurons / Q000637:transplantation; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000601:surgery*; D010865:Pilot Projects; D011699:Putamen / Q000000981:diagnostic imaging / Q000601:surgery*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000601:surgery*; D014055:Tomography, Emission-Computed
C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine