PREVENTION OF DOPAMINERGIC NEURON DEATH BY ADENOASSOCIATED VIRUS VECTOR-MEDIATED GDNF GENE-TRANSFER IN RAT MESENCEPHALIC CELLS IN-VITRO

Glial cell line-derived neurotrophic factor (GDNF) is known as a poten t neurotrophic factor for dopaminergic neurons. Since adeno-associated virus (AAV) vector is a suitable vehicle for gene transfer into neuro ns, rat E14 mesencephalic cells were transduced with an AAV vector exp ressing GDNF. When compared with mock transduction, a larger number of dopaminergic neurons survived in AAV-GDNF-transduced cultures (234% a nd 325% of controls at 1 and 2 weeks, respectively; P < 0.01). Further more, the dopaminergic neurons in the latter cultures grew more promin ent neurites than those in the former. These findings suggest that AAV vector-mediated GDNF gene transfer may prevent dopaminergic neuron de ath, and is therefore a logical approach for the treatment of Parkinso n's disease. (C) 1998 Elsevier Science Ireland Ltd.