Reversal of L-DOPA-induced dyskinesia by recombinant AAV-mediated gene transfer

Objective: To reduce L-DOPA-induced dyskinesia by viral vector gene transfer. Background: Long-term L-DOPA treatment in Parkinson's disease can induce severe dyskinesia in Parkinsonian patients. The appearance of dyskinesia is at least in part due to the intermittent pulsatile administration of L-DOPA, since continuous infusion of L-DOPA in patients can reduce L-DOPA-induced dyskinesia. Methods: In this study we used recombinant AAV-mediated gene transfer of tyrosine hydroxylase, the rate-limiting enzyme for synthesis of dopamine, and its cofactor synthesizing enzyme, GTP cyclohydrolase 1, to locally and continu…