Motor and cognitive improvements in patients with Huntington's disease after neural transplantation

A C Bachoud-Lévi, P Rémy, J P Nguyen, P Brugières, J P Lefaucheur, C Bourdet, S Baudic, V Gaura, P Maison, B Haddad, M F Boissé, T Grandmougin, R Jény, P Bartolomeo, G Dalla Barba, J D Degos, F Lisovoski, A M Ergis, E Pailhous, P Cesaro, P Hantraye, M Peschanski
Lancet 2000 December 9, 356 (9246): 1975-9

BACKGROUND: Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease.

METHODS: After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity.

FINDINGS: The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two.

INTERPRETATION: Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease.

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