Seminars in Neurosurgery 2001; 12(2): 245-252
DOI: 10.1055/s-2001-17130
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Neurotransplantation and Protective Therapy for Movement Disorders

Roy A. E. Bakay
  • Rush Presbyterian-St. Luke's Medical Center, Chicago Institute of Neurosurgery and Neuroresearch, Chicago, IL
Further Information

Publication History

Publication Date:
13 September 2001 (online)

ABSTRACT

Over the past decade a number of advances in cell biology opened new frontiers for surgical treatment of movement disorders. Neurotransplantation as replacement therapy has recently undergone a proof of principle but it is still not fully accepted. The newest surgical approach is protective therapy where innovative techniques are still being developed. Although this has the greatest promise for the future, it also has the greatest number of technical hurdles to overcome before it can become standard therapy. The present status of these new surgical interventions for Parkinson's disease (PD) is reviewed and clinical results are discussed.

REFERENCES

  • 1 Bakay R AE, Kordower J, Starr P. Restorative surgical therapies for Parkinson's disease.  CNS Regeneration . 1999;  14 389-417
  • 2 Boyer K L, Bakay R AE. The history, theory, and present status of brain transplantation.  Neurosurg Clin N Amer . 1995;  6(1) 113-125
  • 3 Defer G, Geny C, Ricolfi F. Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach.  Brain . 1996;  119 41-50
  • 4 Folkerth R, Durso R. Survival and proliferation of nonneural tissues, with obstruction of cerebral ventricles, in a parkinsonian patient treated with fetal allografts.  Neurology . 1996;  46 1219-1224
  • 5 Freed, C, Breeze R, Rosenberg N. Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease.  N Engl J Med . 1992;  327(22) 1549-1555
  • 6 Freed C, Greene P, Breeze R. Transplantation of embryonic dopamine neurons for severe Parkinson's disease.  N Engl J Med . 2001;  344 710-719
  • 7 Freeman T, Olanow C, Hauser R. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease.  Ann Neurol . 1995;  38 379-388
  • 8 Freeman T, Sanberg P, Nauert G, Boss B, Spector D, Olanow C. The influence of donor age on the survival of solid and suspension intraparenchymal human embryonic nigral grafts.  Cell Transplant . 1995;  4 141-154
  • 9 Hauser R A, Freeman T B, Snow B J. Long-term evaluation of bilateral fetal nigral transplantation in Parkinson's disease.  Arch Neurol . 1999;  56 179-187
  • 10 Henderson B T, Clough C G, Hughes R C, Hitchcock E R, Kenny B G. Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease.  Arch Neurol . 1991;  48 822-827
  • 11 Hitchcock E. Current trends in neural transplantation.  Neurol Res . 1995;  17 33-37
  • 12 Hitchcock E, Whitwell H, Sofroniew M, Bankiewicz K. Survival of TH-positive and neuromelanin-containing cells in patients with Parkinson's disease after intrastriatal grafting of fetal ventral mesencephalon [abstract].  Exp Neurol . 1994;  129 3
  • 13 Hoffer B, Leenders K, Young D. Eighteen-month course of two patients with grafts of fetal dopamine neurons for severe Parkinson's disease.  Exp Neurol . 1992;  188 243-252
  • 14 Huang S, Pei G, Kang F. Transplant operation of human fetal substantia nigra tissue to caudate nucleus in Parkinson's disease: first clinical trials.  Clin J Neurosurg . 1989;  5(3) 210-213
  • 15 Iacono R, Tang Z, Mazziotta J, Grafton S, Hoehn M. Bilateral fetal grafts for Parkinson's disease: 22 months' results.  Stereotact Funct Neurosurg . 1992;  58 84-87
  • 16 Jacques D B, Kopyov O V, Eagle K S, Carter T, Lieberman A. Outcomes and complications of fetal tissue transplantation in Parkinson's disease.  Stereotact Funct Neurosurg . 1999;  72 219-224
  • 17 Kopyov O, Jacques D, Lieberman A, Duma C, Rogers R. Clinical study of fetal mesencephalic intracerebral transplants for the treatment of Parkinson's disease.  Cell Transplant . 1996;  5 327-337
  • 18 Kordower J, Freeman T, Snow B. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease.  N Engl J Med . 1995;  332 1118-1124
  • 19 Kordower J H, Freeman T B, Chen E Y. Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson's disease.  Mov Disord . 1998;  13 383-393
  • 20 Lindvall O. Neural transplantation: a hope for patients with Parkinson's disease.  NeuroReport . 1997;  8(14) iii-x
  • 21 Lindvall O, Brundin P, Widner H. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease.  Science . 1990;  247 574-577
  • 22 Lindvall O, Sawle G, Widner H. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease.  Ann Neurol . 1994;  35 172-180
  • 23 Lopez-Lozano J, Bravo B, Brera B. Long-term follow-up in 10 Parkinson's disease patients subjected to fetal brain grafting into a cavity in the caudate nucleus: the Clinica Puerta de Hierro experience.  Transplantation Proc . 1995;  27 1395-1400
  • 24 Lopez-Lozano J, Bravo G, Brera B. Long-term improvement in patients with severe Parkinson's disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow-up in 10 patients.  J Neurosurg . 1997;  86 931-942
  • 25 Madrazo I, Franco-Bourland R, Ostrosky-Solid F. Fetal homotransplants (ventral mesencephalon and adrenal tissue) to the striatum of Parkinson subjects.  Arch Neurol . 1990;  47 1281-1285
  • 26 Meyer C, Detta A, Kudoh C. Hitchcock's experimental series of focal implants for Parkinson's disease: cografting of ventral mesencephalon and striatum.  Acta Neurochir Suppl . 1995;  64 1-4
  • 27 Molina H, Quinones-Molina R, Munoz J. Neurotransplantation in Parkinson's disease: from open microsurgery to bilateral stereotactic approach: first clinical trial using microelectrode recording.  Stereotact Funct Neurosurg . 1994;  62 204-208
  • 28 Peschanski M, Defer G, N'Guyen J. Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson's disease following intrastriatal transplantation of foetal ventral mesencephalon.  Brain . 1994;  117 487-499
  • 29 Redmond D, Leranth C, Spencer D. Fetal neural graft survival [letter].  Lancet . 1990;  336 820-822
  • 30 Remy P, Samson Y, Hantraye P. Clinical correlates of [18-F] fluorodopa uptake in five grafted parkinsonian patients.  Ann Neurol . 1995;  38 580-588
  • 31 Spencer D, Robbins R, Naftolin F. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of parkinsonian patients: functional effects for 18 months.  New Engl J Med . 1992;  327(22) 1541-1548
  • 32 Subrt O, Tichy M, Vladyka V, Hurt K. Grafting of fetal dopamine neurons in Parkinson's disease: the Czech experience with severe akinetic patients.  Acta Neurochir Suppl (Wien) . 1991;  52 51-53
  • 33 Wenning G, Odin P, Morrish P. Short-and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease.  Ann Neurol . 1997;  42 95-107
  • 34 Widner H, Tetrud J, Rehncrona S. Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).  N Engl J Med . 1992;  327 1556-1563
  • 35 Yurek D, Collier T, Sladek J. Embryonic mesencephalic and striatal co-grafts: development of grafted dopamine neurons and functional recovery.  Exp Neurol . 1990;  109 191-199
  • 36 Zabek M, Mazurowski W, Dymecki J. A long-term follow-up of fetal dopaminergic neuronal transplantation into the brains of three parkinsonian patients.  Res Neurol Neurosci . 1994;  6 97-106
  • 37 Widner H, Brundin P. Immunological aspects of grafting in the mammalian central nervous system: a review and speculative synthesis.  Brain Res . 1998;  Rev 13 287-324
  • 38 Grabowska A, Lampson L. Expression of class I and II major histocompatibility (MHC) antigens in the developing of CNS.  J Neural Transplantation Plasticity . 1992;  3 204-205
  • 39 Lawrence J, Morris R, Wilson D. Mechanisms of allograft rejection in the rat brain.  Neuroscience . 1990;  37 431-462
  • 40 Skoskiewicz M, Colvin R, Scheenberger E. Widespread and elective distribution of major histocompatibility complex-determined antigens in vivo by interferon.  J Exp Med . 1985;  152 1645-1664
  • 41 Poltorak M, Freed W. Immunological reactions induced by intracerebral transplantations: evidence that host microglia but not astroglia are the antigen-presenting cells.  Exp Neurol . 1989;  103 222-233
  • 42 Vidovic M, Sparacia S, Elovitz M, Beneviste E. Induction and regulation of class II major histocompatability complex mRNA expression in astrocytes by interferon-gamma and tumor necrosis factor-alpha.  J Neuroimmunol . 1990;  30 89-200
  • 43 Hirshberg D, Schwartz M. Macrophage recruitment to acutely injured central nervous system is inhibited by a resident factor: a basis for an immune-brain barrier.  J Neuroimmunol . 1995;  61 89-96
  • 44 Bakay R AE, Boyer K L, Freed C R, Ansari A A. Immunological responses to injury and grafting in the central nervous system of nonhuman primates.  Cell Transplant . 1998;  7(2) 109-120
  • 45 Fiandaca M, Bakay R AE, Sweeney K, Chan W. Immunologic response to intracerebral fetal neural allografts in the rhesus monkey.  Prog Brain Res . 1988;  78 287-296
  • 46 Freed C, Breeze R, Schneck S, Bakay R AE, Ansari A. Fetal neural transplantation for Parkinson's disease. In: Clinical Immunology: Principles and Practice New York, NY: Mosby 1996: 1677-1687
  • 47 Kordower J, Styren S, Clarke M, DeKosky S, Olanow C, Freeman T. Fetal grafting for Parkinson's disease: expression of immune markers in two patients with functional fetal nigral implants.  Cell Transplant . 1997;  6 213-219
  • 48 Piccini P, Brooks D J, Bjorklund A. Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient.  Nat Neurosci . 1999;  2 1137-1140
  • 49 Brundin P, Karlsson J, Emgard M. Improving the survival of grafted dopaminergic neurons: a review over current approaches.  Cell Transplant . 2000;  9 179-195
  • 50 Greene P E, Fahn S, Tsai W Y. Severe spontaneous dyskinesias: a disabling complication of embryonic dopaminergic tissue implants in a subset of transplanted patients with advanced Parkinson's disease [abstract].  Mov Disord . 1999;  14 904
  • 51 Mamelak A N, Eggerding F A, Oh D S. Fatal cyst formation after fetal mesencephalic allograft transplant for Parkinson's disease.  J Neurosurg . 1998;  89 592-598
  • 52 Mendez I, Dagher A, Hong M. Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line-derived neurotrophic factor in patients with Parkinson's disease. Report of two cases and technical considerations.  J Neurosurg . 2000;  92 863-869
  • 53 Sladek J R, Collier T J, Elsworth J D, Taylor J R, Roth R H, Redmond D E. Can graft-derived neurotrophic activity be used to direct axonal outgrowth of grafted dopamine neurons for circuit reconstruction in primates?.  Exp Neurol . 1993;  124 134-139
  • 54 Vawter D, Gervais K, Caplan A. Risks of fetal tissue donation to women.  J Neural Transplantation Plasticity . 1992;  3 322
  • 55 Svendsen C, Smith A. New prospects for human stem-cell therapy in the nervous system.  Trends Neurosci . 1999;  22 357-364
  • 56 Deacon T, Schumacher J, Dinsmore J. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease.  Nature Med . 1995;  3 350-353
  • 57 Edge A, Dinsmore J. Xenotransplantation in the central nervous system.  Xeno . 1997;  5(2) 23-25
  • 58 Deacon T, Pakzaban P, Burns L, Dinsmore J, Isacson O. Cytoarchitectonic development, axon-glia relationships, and long distance axon growth of porcine striatal xenografts in rats.  Exp Neurol . 1994;  130 151-167
  • 59 Isacson O, Deacon T, Pakzaban P, Galpern W, Dinsmore J, Burns L. Transplanted xenogenetic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres.  Nature Med . 1995;  1 1189-1194
  • 60 Wu C, De Zhou M, Bao X. The combined method of transplantation of fetal substantia nigra and stereotactic thalamotomy for Parkinson's disease.  Br J Neurosurg . 1994;  8 709-716
  • 61 Fisher L J, Jinnah H A, Kale L C, Higgins G A, Gage F H. Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-dopa.  Neuron . 1991;  6 371-380
  • 62 Jiao S, Gurevich V, Wolff J. Long-term correction of a rat model of Parkinson's disease by gene therapy.  Nature . 1993;  362 450-453
  • 63 Anton R. Neural-targeted gene therapy for rodent and primate hemiparkinsonism.  Exp Neurol . 1994;  127 199-206
  • 64 Bredesen D. Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behavior, and dopamine release.  Exp Brain Res . 1988;  70 192-208
  • 65 Bjorklund A, Lindvall O. Dopamine in dendrites of the substantia nigra neurons: suggestions for a role in dendritic terminals.  Brain Res . 1975;  83 531-537
  • 66 Johnson R, Becker J. Intranigral grafts of fetal ventral mesencephalic tissue in adult 6-hydroxydopamine-lesioned rats can induce behavioral recovery.  Cell Transplant . 1997;  6 267-276
  • 67 Nikkah G, Bentlage C, Cunningham M G, Bjorklund A. Intranigral fetal dopamine grafts induce behavioral compensation in the rat Parkinson mode.  J Neurosci . 1994;  14 3449-3461
  • 68 Starr P A, Wichmann T, van Horne C. Intranigral transplantation of fetal substantia nigra allograft in the hemiparkinsonian rhesus monkey.  Cell Transplant . 1999;  8 37-45
  • 69 Lindsay R. Neuron saving schemes [news and comments].  Nature . 1995;  373 289-290
  • 70 Lin L, Doherty D, Lile J, Bextesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.  Science . 1993;  260 1130-1132
  • 71 Beck K, Valverde J, Alexi T. Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.  Nature . 1995;  373 339-341
  • 72 Kearns C, Gash D. GDNF protects nigral dopamine neurons against 6-hydroxydopamine in vivo.  Brain Res . 1995;  672 104-111
  • 73 Tomac A, Lindqvist E, Lin L. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo.  Nature . 1995;  373 335-339
  • 74 Gash D, Zhang Z, Ovadia A. Functional recovery in parkinsonian monkeys treated with GDNF.  Nature . 1996;  380 252-255
  • 75 Kordower J, Palfi S, Chen E Y. Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease.  Ann Neurol . 1999;  46(3) 419-424
  • 76 Kordower J, Emborg M, Bloch J. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.  Science . 2000;  290 767-773
  • 77 Hughes A J, Daniel S E, Kilford L, Lees A J. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinicopathological study of 100 cases.  J Neurol Neurosurg Psychiatry . 1992;  55 181-184