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Striatal delivery of CERE‐120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys

Neurturin (NTN) is a potent survival factor for midbrain dopaminergic neurons. CERE‐120, an adeno‐associated virus type 2 (AAV2) vector encoding human NTN (AAV2‐NTN), is currently being developed as a potential therapy for Parkinson's disease. This study examined the bioactivity and safety/tolerability of AAV2‐NTN in the aged monkey model of nigrostriatal dopamine insufficiency. Aged rhesus monkeys received unilateral injections of AAV2‐NTN into the caudate and putamen, with each animal therefore serving as its own control. Robust expression of NTN within the nigrostriatal system was observed 8 months postadministration. 18F‐fluorodopa imaging using positron emission tomography revealed statistically significant increases in 18F‐fluorodopa uptake in the injected striatum compared with the uninjected side at 4 and 8 months. In addition, at 8 months postadministration, a significant enhancement in tyrosine hydroxylase immunoreactive fibers and an increase in the number of tyrosine hydroxylase immunoreactive cells was observed in the AAV2‐NTN injected striatum compared with the uninjected side. Robust activation of phosphorylated extracellular signal‐regulated kinase immunoreactivity in the substantia nigra was also observed. Histopathological analyses revealed no adverse effects of AAV2‐NTN in the brain. Collectively, these results are consistent with the neurotrophic effects of NTN on the dopaminergic nigrostriatal system and extend the growing body of evidence supporting the concept that AAV2‐NTN may have therapeutic benefit for Parkinson's disease. © 2007 Movement Disorder Society