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Monday March 16 2009

Parkinson’s disease: use of PET imaging to monitor the therapeutic efficacy of intracerebral gene transfer

CEA
These results concern the development and validation of a method of therapeutic monitoring for gene therapy for Parkinson’s disease.


In a joint three-way study conducted by MIRCen (I²BM, CEA/Fontenay-aux-Roses), SHFJ (I²BM, CEA/Orsay) and Lund University (Wallenberg Institute, Sweden), researchers have shown that it is possible to use a carbon-11 labelled tracer for dopaminergic receptors, [11C]raclopride, for the non-invasive measurement (by PET imaging) in Parkinson patients of the ability of gene therapy to restore endogenous concentrations of dopamine. In the Parkinson rat model, the low level of dopamine is associated with the binding of a large quantity of this tracer on dopaminergic receptors. This binding is normalised after restoration of normal levels of dopamine by the intracerebral transfer of the genes responsible for its biosynthesis. The use of [11C]raclopride thus allows indirect quantification of available dopamine before and after the gene transfer, and an evaluation of the efficacy of this gene therapy. This imaging protocol, developed and validated in animals, will be adapted for Parkinson patients in a second phase 1-2 clinical trial currently being prepared in Sweden.