Striatal neural grafting improves cortical metabolism in Huntington's disease patients.
Huntington's disease is a hereditary disease in which degeneration of neurons in the striatum leads to motor and cognitive deficits. Foetal striatal allografts reverse these deficits in phenotypic models of Huntington's disease developed in primates. A recent open-label pilot study has shown some clinical improvement or stabilization in three out of five Huntington's disease patients who received bilateral striatal grafts of foetal neurons. We show here that the clinical changes in these three patients were associated with a reduction of the striatal and cortical hypometabolism, demonstrating that grafts were able to restore the function of striato-cortical loops. Conversely, in the two patients not improved by the grafts, striatal and cortical hypometabolism progressed over the 2-year follow-up. Finally, detailed anatomical-functional analysis of the grafted striata, enabled by the 3D fusion of MRI and metabolic images, revealed considerable heterogeneity in the anatomic and metabolic profiles of grafted tissue, both within and between Huntington's disease patients. Our results demonstrate the usefulness of PET measurements of brain glucose metabolism in understanding the effects of foetal grafts in patients with Huntington's disease.
Gaura
Véronique
V
URA CEA-CNRS 2210, 4 place du général Leclerc, 91401 Orsay Cedex, France.
Bachoud-Lévi
Anne-Catherine
AC
Ribeiro
Maria-Joao
MJ
Nguyen
Jean-Paul
JP
Frouin
Vincent
V
Baudic
Sophie
S
Brugières
Pierre
P
Mangin
Jean-François
JF
Boissé
Marie-Françoise
MF
Palfi
Stéphane
S
Cesaro
Pierre
P
Samson
Yves
Y
Hantraye
Philippe
P
Peschanski
Marc
M
Remy
Philippe
P
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016380:Brain Tissue Transplantation; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D004453:Echoencephalography; D005260:Female; D016332:Fetal Tissue Transplantation; D005500:Follow-Up Studies; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D001786:Blood Glucose