Gene therapy with AAV 2‐ CDNF provides functional benefits in a rat model of P arkinson's disease

Cerebral dopamine neurotrophic factor ( CDNF ) protein has been shown to protect the nigrostriatal dopaminergic pathway when given as intrastriatal infusions in rat and mouse models of P arkinson's disease ( PD ). In this study, we assessed the neuroprotective effect of CDNF delivered with a recombinant adeno‐associated viral ( AAV ) serotype 2 vector in a rat 6‐hydroxydopamine (6‐ OHDA ) model of PD . AAV 2 vectors encoding CDNF , glial cell line–derived neurotrophic factor ( GDNF ), or green fluorescent protein were injected into the rat striatum. Protein expression analysis showed that our AAV 2 vector efficiently delivered the neurotrophic factor genes into the brain and gave rise to a long‐lasting expression of the proteins. Two weeks after AAV 2 vector injection, 6‐ OHDA was injected into the rat striatum, creating a progressive degeneration of the nigrostriatal dopaminergic system. Treatment with AAV 2‐ CDNF resulted in a marked decrease in amphetamine‐induced ipsilateral rotations while it provided only partial protection of tyrosine hydroxylase ( TH )‐immunoreactive cells in the rat substantia nigra pars compacta and TH ‐reactive fibers in the striatum. Results from this study provide additional evidence that CDNF can be considered a potential treatment of P arkinson's disease.