J. ERIC AHLSKOG, PH.D.M.D. Mayo Clinic Proceedings

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Cerebral Transplantation for Parkinson's Disease: Current Progress and Future Prospects J. ERIC AHLSKOG, PH.D.M.D. Mayo Clinic Proceedings Volume 68, Issue 6, Pages 578-591 (June 1993) DOI: 10.1016/S0025-6196(12)60373-5 Copyright © 1993 Mayo Foundation for Medical Education and Research Terms and Conditions

Fig. 1 Cells within substantia nigra project to striatum (caudate and putamen) and then release neurotransmitter dopamine. This system degenerates in idiopathic Parkinson's disease. See text for details of various therapeutic strategies and animal models of parkinsonism. MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Mayo Clinic Proceedings 1993 68, 578-591DOI: (10.1016/S0025-6196(12)60373-5) Copyright © 1993 Mayo Foundation for Medical Education and Research Terms and Conditions

Fig. 2 Genome of brain cells can be directly altered by transfection with retrovirus or herpes simplex virus 1 vectors. For example, inducing striatal cells to synthesize and secrete dopamine through these recombinant DNA techniques should be theoretically possible. This approach could replenish dopamine neurotransmission in dopamine-depleted brains of patients with Parkinson's disease. Mayo Clinic Proceedings 1993 68, 578-591DOI: (10.1016/S0025-6196(12)60373-5) Copyright © 1993 Mayo Foundation for Medical Education and Research Terms and Conditions

Fig. 3 Immortalization of cells for transplantation has potential for development of tumor. To counter this possibility, one strategy involves transformation of cells by using a conditional oncogene. See text for details about temperature-related effects. Mayo Clinic Proceedings 1993 68, 578-591DOI: (10.1016/S0025-6196(12)60373-5) Copyright © 1993 Mayo Foundation for Medical Education and Research Terms and Conditions

Fig. 4 Bredesen and associates70 demonstrated feasibility of transplanting immortalized neuronal stem cell lines by using a recombinant temperature-sensitive oncogene strategy, as illustrated in Figure 3. In their model, the immortalized cells received β-galacto-sidase marker and neomycin-metabolizing genes through recombinant techniques with use of a retrovirus vector. Adding neomycin to medium destroyed nontransfected cells and provided a means of selection. See text for outcome of transplanted cell lines. Mayo Clinic Proceedings 1993 68, 578-591DOI: (10.1016/S0025-6196(12)60373-5) Copyright © 1993 Mayo Foundation for Medical Education and Research Terms and Conditions