IMPROVEMENT OF NEUROLOGICAL DEFICITS IN 6-HYDROXYDOPAMINE-LESIONED RATS AFTER TRANSPLANTATION WITH ALLOGENEIC SIMIAN-VIRUS-40 LARGE TUMOR-ANTIGEN GENE-INDUCED IMMORTALIZED DOPAMINE CELLS

The replacement of dopamine (DA) by DA neuron transplants in the treat ment of advanced Parkinson disease (PD) is a rational approach. Becaus e of limitations associated with fetal tissue transplants, a clone (1R B(3)AN(27)) of simian virus 40 large tumor antigen (LTa) gene induced immortalized DA neurons were used in this study, These allogeneic immo rtalized dopamine neurons, when grafted into striata of normal rats, d id not divide, did not form tumors, did not produce LTa, did not exten d neurites to host neurons, and were not rejected, for as long as 13 m onths after transplantation. Grafted cells when recultured in vitro re sumed cell proliferation and LTa production, suggesting the presence o f a LTa gene-inhibiting factor in the brain, The grafting of undiffere ntiated and differentiated 1RB(3)AN(27) cells or differentiated murine neuroblastoma (NBP2) cells into striata of 6-hydroxydopamine-lesioned rats (an animal model of PD) caused a time-dependent improvement in n eurological deficits (reduction in the methamphetamine-induced turning rate),At 3 months after transplantation, 100% of the animals receivin g differentiated 1RB(3)AN(27) cells, 63% of the animals receiving undi fferentiated 1RB(3)AN(27) cells, 56% of the animals receiving differen tiated NBP2 cells, and 0% of the sham-transplanted animals showed impr ovements in neurological deficits, At 6 months after transplantation, there was a progressive increase in spontaneous recovery in sham-trans planted animals, These results suggest that immortalized DA neurons sh ould be further studied for their potential use in transplant therapy in advanced PD patients.