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Brain Advance Access published online on November 7, 2003
Brain, doi:10.1093/brain/awh003
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© 2003 The Guarantors of Brain

Article

Striatal neural grafting improves cortical metabolism in Huntington’s disease patients

Véronique Gaura 1, Anne-Catherine Bachoud-Lévi 2, Maria-Joao Ribeiro 3, Jean-Paul Nguyen 2, Vincent Frouin 3, Sophie Baudic 4, Pierre Brugières 2, Jean-François Mangin 3, Marie-Françoise Boissé 2, Stéphane Palfi 5, Pierre Cesaro 2, Yves Samson 6, Philippe Hantraye 1, Marc Peschanski 2, and Philippe Remy 7*

1 URA CEA-CNRS 2210, 4 place du général Leclerc, 91401 Orsay Cedex, France; CEA, Service Hospitalier Frédéric Joliot, DRM, 4 place du général Leclerc, 91401 Orsay Cedex, France
2 Département de Neurosciences, CHU Henri Mondor, AP-HP et Faculté de Médecine Paris XII, 51 avenue du Mal de Lattre de Tassigny, 94010 Créteil Cedex, France; INSERM U421, IM3, Faculté de Médecine Paris XII, 8 rue du général Sarrail, 94010 Créteil Cedex, France
3 CEA, Service Hospitalier Frédéric Joliot, DRM, 4 place du général Leclerc, 91401 Orsay Cedex, France
4 INSERM U421, IM3, Faculté de Médecine Paris XII, 8 rue du général Sarrail, 94010 Créteil Cedex, France
5 URA CEA-CNRS 2210, 4 place du général Leclerc, 91401 Orsay Cedex, France; Département de Neurosciences, CHU Henri Mondor, AP-HP et Faculté de Médecine Paris XII, 51 avenue du Mal de Lattre de Tassigny, 94010 Créteil Cedex, France
6 CEA, Service Hospitalier Frédéric Joliot, DRM, 4 place du général Leclerc, 91401 Orsay Cedex, France; Urgences Cérébro-Vasculaires, CHU Pitié-Salpétrière, Paris, France
7 URA CEA-CNRS 2210, 4 place du général Leclerc, 91401 Orsay Cedex, France; CEA, Service Hospitalier Frédéric Joliot, DRM, 4 place du général Leclerc, 91401 Orsay Cedex, France; Département de Neurosciences, CHU Henri Mondor, AP-HP et Faculté de Médecine Paris XII, 51 avenue du Mal de Lattre de Tassigny, 94010 Créteil Cedex, France

* Corresponding author. E-mail: remy{at}shfj.cea.fr.

Received 9 May 2003 ; revised 10 July 2003 ; accepted 17 July 2003

Abstract

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.

Keywords: cortex; foetal graft; Huntington’s disease; metabolism; striatum
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