Molecular imaging of gene therapy. The future in Parkinson's disease therapy?

Molecular imaging is a rapidly evolving field based on concerted research and new technical developments spanning on multiple disciplines. Especially for the development of successful implementation of new therapeutic modalities in PD, such as gene therapy, imaging of endogenous effector gene expression and imaging of cells as well as vector-mediated gene expression in vivo will be of critical importance. In a primate PD model, the therapeutic effect of lentiviral vector-mediated transduction of glial cell line-derived neurotrophic factor (GDNF) has been shown by measuring the improvement in endogenous enzymatic AADC activity with 18-Fluorodopa-PET. The lenti-GDNF-mediated improvement in nigrostriatal functioning correlated with improvements in motor tasks, with positive GDNF expression and with an increased number of tyrosine hydroxylase-expressing nigrstriatal neurons at autopsy. Moreover, an efficient adeno-associated virus vector-mediated transfer of the AADC gene directly has been achieved after convection-enhanced delivery in a primate model of PD. Other research efforts are directed at the virus-mediated transduction of the glutamate-decarboxylase (GAD) gene into STN neurons in order to convert them into inhibitory GABAergic efferents projecting to connected basal ganglia nuclei, such as the substantia nigra. This approach might reduce the STN-mediated glutamatergic excitotoxicity in PD which is considered an important factor in PD progression.