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Fetal Tissue Transplantation for Patients with Parkinson’s Disease

A Database of Published Clinical Results

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Abstract

Over the past 13 years approximately 300 patients with Parkinson’s disease have received transplants of human fetal dopamine cells in an attempt to reduce or control disease symptoms. Many of these patients have had improvements in their motor skills and a reduction in their daily levodopa administration. However, improvements are far from guaranteed and questions need to be answered before this technique can be widely applied. To help address some of these issues, a search of all the published results of patients with Parkinson’s disease transplanted with human fetal tissue was conducted. This generated a database of 70 transplant recipients who had their levodopa administration and clinical benefit reported both prior to transplant and at least 6 months post-transplant. Furthermore, the number of years of disease onset prior to transplant was available for all recipients. This database was examined for motor improvement and reduction in levodopa dosage for up to 2 years post-transplant to determine the effects of time on transplant outcome. The database showed that most recipients had significant improvements in motor skills and levodopa administration, and that most benefits were observed in the first 6 months post-transplant. In addition, the database demonstrated that the number of years of disease onset prior to transplantation was not a predictor of patient outcome 1-year post-transplant. Current and future directions in fetal tissue transplantation research and replacements for fetal tissue are discussed.

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References

  1. Rajput AH. Frequency and cause of Parkinson’s disease. Can J Neurol Sci 1992; 19(1): 103–7

    PubMed  CAS  Google Scholar 

  2. Ehringer H and Hornykiewicz O. Verteilung von noradrenalin and dopamin (3-hydroxytyramin) im gehirn des menschen und ihr verhalten bei erkrankungen des extrapyramidalen systems. Klin Wochenschr 1960; 38: 1236–9

    Article  PubMed  CAS  Google Scholar 

  3. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967 Feb; 276(7): 374–9

    Article  PubMed  CAS  Google Scholar 

  4. Rascol O, Brooks DJ, Korczyn AD, et al. A five year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med 2000 May; 342(20): 1482–91

    Article  Google Scholar 

  5. Sax DS, Tarsy D. Side effects of L-dopa. N Engl J Med 1971 Oct; 285(18): 1033

    PubMed  CAS  Google Scholar 

  6. Kaye JA, Feldman RG. The role of L-dopa holiday in the long-term management of Parkinson’s disease. Clin Neuropharmacol 1986; 9(1): 1–13

    Article  PubMed  CAS  Google Scholar 

  7. Tasker RR, Lang AE, Lozano AM. Pallidal and thalamic surgery for Parkinson’s disease. Exp Neurology 1997 Mar; 144(1): 35–40

    Article  CAS  Google Scholar 

  8. Starr PA, Vitek JL, Bakay RA. Deep brain stimulation for movement disorders. Neurosurg Clin N Am 1998 Apr; 9(2): 381–402

    PubMed  CAS  Google Scholar 

  9. Lindvall O, Sawle G, Widner H, et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol 1994; 35(2): 172–9

    Article  PubMed  CAS  Google Scholar 

  10. Lindvall O, Rehncrona S, Brunin P, et al. Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease. Arch Neurol 1989 Jun; 46: 615–31

    Article  PubMed  CAS  Google Scholar 

  11. Lindvall O, Brundin P, Widner H, et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 1990 Feb 2; 247: 574–7

    Article  PubMed  CAS  Google Scholar 

  12. Freed CR, Breeze RE, Rosenberg SA, et al. Transplantation of human fetal dopamine cells for Parkinson’s disease. Arch Neurol 1990 May; 47: 505–12

    Article  PubMed  CAS  Google Scholar 

  13. Henderson BT, Clough CG, Hughes RC, et al. Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advance Parkinson’s disease. Arch Neurol 1991 Aug; 48: 822–7

    Article  PubMed  CAS  Google Scholar 

  14. Freed CR, Breeze RE, Rosenberg NL, et al. Survival of implanted fetal dopamine cells and neurological improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med 1992 Nov; 327: 1549–55

    Article  PubMed  CAS  Google Scholar 

  15. Freed CR, Breeze RE, Rosenberg NL, et al. Embryonic dopamine cell implants as a treatment for the second phase of Parkinson’s disease. Replacing failed nerve terminals. Adv Neurol 1993; 60: 721–8

    PubMed  CAS  Google Scholar 

  16. Lindvall O, Widner H, Rehncrona S, et al. Transplantation of fetal dopamine neurons in Parkinson’s disease. Ann Neurol 1992; 31: 155–65

    Article  PubMed  CAS  Google Scholar 

  17. Spencer DD, Robbins RJ, Naftolin F, et al. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N Engl J Med 1992 Nov; 327: 1541–8

    Article  PubMed  CAS  Google Scholar 

  18. Widner H, Tetrad J, Rehncrona S. Bilateral fetal mesencephalic grafting in two patients with Parkinsonism induced by 1-methyl-4-phenyl-l,2,3,6-tetrahydropyrine (MPTP). N Engl J Med 1992 Nov 23; 327: 1556–63

    Article  PubMed  CAS  Google Scholar 

  19. Peschanski M, Defer G, N’guyen JP, et al. 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: 487–99

    Article  PubMed  Google Scholar 

  20. Defer GL, Geny C, Ricolfi F. Long-term outcome of unilaterally transplanted Parkinson’s patients. Brain 1996; 119: 41–50

    Article  PubMed  Google Scholar 

  21. Kordower JH, Freeman TB, Snow BJ, et al. 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 Apr 27; 332: 1118–24

    Article  PubMed  CAS  Google Scholar 

  22. Freeman TB, Olanow CW, Hauser RA, Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson’s disease. Ann Neurol 1995; 38(3): 379–88

    Article  PubMed  CAS  Google Scholar 

  23. Freed CR, Breeze RE, Scheneck SA, et al. Fetal Neural Transplantation for Parkinson’s disease. In: Rich RR, editor. Clinical immunology: principles and practice. St Louis (MO): Mosby-Year Book Inc., 1995: 1677–87

    Google Scholar 

  24. Kopyov OV, Jacques D, Lieberman A, et al. Clinical study of fetal mesencephalic intracerebral transplants for the treatment of Parkinson’s disease. Cell Transplant 1996; 5: 327–37

    Article  PubMed  CAS  Google Scholar 

  25. Wenning GK, Odin P, Morrish P, et al. Short and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson’s disease. Ann Neurol 1997 Jul; 42(1): 95–107

    Article  PubMed  CAS  Google Scholar 

  26. Mendez I, Dagher A, Hong M, et al. 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. J Neurosurg 2000 May; 92: 863–9

    Article  PubMed  CAS  Google Scholar 

  27. Hagell P, Crabb L, Pogarell O, et al. Health-related quality of life following bilateral intrastriatal transplantation in Parkinson’s disease. Mov Disord 2000; 15(2): 224–9

    Article  PubMed  CAS  Google Scholar 

  28. Hauser RA, Freeman TB, Snow BJ, et al. Long-term evaluation of bilateral fetal nigral transplantation in Parkinson disease. Arch Neurol 1999 Feb; 56: 179–87

    Article  PubMed  CAS  Google Scholar 

  29. Brundin P, Pogarell O, Hagell P, et al. Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson’s disease. Brain 2000 Jul; 123(7): 1380–90

    Article  PubMed  Google Scholar 

  30. Jacques DB, Kopyov OV, Eagle KS, et al. Outcomes and complications of fetal tissue transplantation in Parkinson’s disease. Stereotact Funct Neurosurg 1999; 72: 219–24

    Article  PubMed  CAS  Google Scholar 

  31. Widner H. The case for neural tissue transplantation as a treatment for Parkinson’s disease. Adv Neurol 1999; 80: 641–9

    PubMed  CAS  Google Scholar 

  32. Lindvall O, Backlund EO, Farde L. Transplantation in Parkinson’s disease: two cases of adrenal medullary grafts. Ann Neurol 1987 Oct; 22(4): 457–68

    Article  PubMed  CAS  Google Scholar 

  33. Madrazo I, Drucker-Colin T, Daiz V. Open microsurgical autograft of adrenal medulla to the right caudate nucleus in with intractable Parkinson’s disease. N Engl J Med 1987 Apr; 316(14): 831–3

    Article  PubMed  CAS  Google Scholar 

  34. Goetz CG, Olanow CW, Koller WC, et al. Multicenter study of autologous adrenal medullary transplantation to the corpus patients with advanced Parkinson’s disease. N Eng J Med 1989 Feb; 320(6): 337–41

    Article  CAS  Google Scholar 

  35. Olanow CW, Koller W, Goetz CG, et al. Autologous transplantation of adrenal medulla in Parkinson’s disease. 18-month releases. Arch Neurol 1990 Dec; 47(12): 1286–9

    Article  PubMed  CAS  Google Scholar 

  36. 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 1997 Mar; 3: 350–3

    Article  PubMed  CAS  Google Scholar 

  37. Schumacher JM, Ellias SA, Palmer EP, et al. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology 2000 Mar 14; 54(5): 1042–50

    Article  PubMed  CAS  Google Scholar 

  38. Stromberg I, Herrera-Marachitz M, Ungerstedt U. Chronic implants of chromaffin tissue into the dopamine-denervated striatum. Effects of NGF on graft survival, fiber growth and rotational behavior. Exp Brain Res 1985; 60(2): 335–49

    Article  PubMed  CAS  Google Scholar 

  39. Kordower JH, Fiandaca MS, Notter MF, et al. NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells. J Neurosurgery 1990 Sep; 73(3): 418–28

    Article  CAS  Google Scholar 

  40. Kordower JH, Goetz CG, Freeman TB, et al. Dopaminergic transplants in patients with Parkinson’s disease: neuroanatomical correlates of clinical recovery. Exp Neurol 1997 Mar; 144(1): 41–6

    Article  PubMed  CAS  Google Scholar 

  41. Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 1970 Dec 18; 24: 485–93

    Article  PubMed  CAS  Google Scholar 

  42. Lund RD, Hauschka SD. Transplanted neural tissue develops connections with host rat brain. Science 1976 Aug; 193: 582–4

    Article  PubMed  CAS  Google Scholar 

  43. Björklund A, Stenevi U. Reformation of the several septohippocampal cholinergic pathway in the adult rat by transplanted septal neurons. Cell Tissue Res 1977 Dec 19; 185: 289–302

    Article  PubMed  Google Scholar 

  44. Björklund A, Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 1979; 177: 555–60

    Article  PubMed  Google Scholar 

  45. Perlow MJ, Freed WJ, Hoffer BJ. Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science 1979; 204: 555–60

    Article  Google Scholar 

  46. Schmidt RH, Björklund A, Stenevi U. Intracerebral grafting of dissociated CNS suspensions: a new approach for neuronal transplantation to deep brain sites. Brain Res 1981; 218: 347–56

    Article  PubMed  CAS  Google Scholar 

  47. Wuerthele SM, Freed WJ, Olson L. Effect of dopamine agonists and antagonists on the electrical activity of substantia nigra neurons transplanted into the lateral ventricle of the rat. Exp Brain Res 1981; 44: 1–10

    Article  PubMed  CAS  Google Scholar 

  48. Schmidt RH, Ingvar M, Lindvall O, et al. Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and [14C]2-deoxy-D-glucose autoradiography. Neurochem 1982 Mar; 38: 737–48

    Article  CAS  Google Scholar 

  49. Mahalik TJ, Finger TE, Stromberg I, et al. Substantia nigra transplants into denervated striatum of the rat: ultrastructure of graft and host interconnections. J Comp Neurol 1985 Oct; 240: 60–70

    Article  PubMed  CAS  Google Scholar 

  50. Dunnett SB, Hernandez TD, Summerfield A, et al. Graft-derived recovery from 6-OHDA lesions: specificity of ventral mesencephalic graft tissue. Exp Brain Res 1988; 71: 411–24

    Article  PubMed  CAS  Google Scholar 

  51. Bakay RA, Fiandaca MS, Barrow DL, et al. Preliminary report on the use of fetal tissue transplantation to correct MPTP-induced Parkinson-like syndrome in primates. Appl Neurophysiol 1985; 48: 58–361

    Google Scholar 

  52. Freed CR, Richards JB, Sabol KE, et al. Fetal neural transplants. In: Beart PM, Woodruff G, Jackson DM, editors. Pharmacology and functional regulation of dopaminergic neurons. London: Macmillan Press, 1988: 353–60

    Google Scholar 

  53. Sladek Jr JR, Collier TJ, Haber SN, et al. Reversal of Parkinsonism by fetal nerve cell transplants in primate brain. Ann N Y Acad Sci 1987; 495: 641–57

    Article  PubMed  Google Scholar 

  54. Taylor JR, Elsworth JD, Roth RH, et al. Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls. Exp Brain Res 1991; 85(2): 335–48

    Article  PubMed  CAS  Google Scholar 

  55. Langsten JW, Ballard P, Teturd JW, et al. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983 Feb; 219(4587): 979–80

    Article  Google Scholar 

  56. Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001 Mar; 344(10): 710–9

    Article  PubMed  CAS  Google Scholar 

  57. Clarkson ED, Freed CR. Development of fetal neural transplantation as a treatment for Parkinson’s disease. Life Sci 1999; 65(22): 2427–37

    Article  PubMed  CAS  Google Scholar 

  58. Hagell P, Schrag A, Piccini P, et al. Sequential bilateral transplantation in Parkinson’s disease. Effects of the second graft. Brain 1999; 1222: 1121–32

    Article  Google Scholar 

  59. Piccini P, Brooks DJ, BjÖrklund A, et al. Dopamine release from nigral transplants visualized in vivo in a Parkinson’s patient. Nature Neurosci 1999 Dec; 2(12): 1137–40

    Article  PubMed  CAS  Google Scholar 

  60. Yurek DM, Steece-Collier K, Collier TJ, et al. Chronic levodopa impairs the recovery of dopamine agonist-induced rotational behavior following neural grafting. Exp Brain Res 1991; 86(1): 97–107

    Article  PubMed  CAS  Google Scholar 

  61. Brundin P, Barbin G, Isacson O, et al. Survival of intracerebrally grafted rat dopamine neurons previously cultured in vitro. Neurosci Lett 1985 Oct; 61(1–2): 79–84

    Article  PubMed  CAS  Google Scholar 

  62. Zawada WM, Zastrow DJ, Clarkson ED, et al. Growth factors improve immediate survival of embryonic dopamine neurons after transplantation into rats. Brain Res 1998; 786: 96–103

    Article  PubMed  CAS  Google Scholar 

  63. Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. Pathophysiologic and clinical implications. N Engl J Med 1988 Apr; 318(14): 876–80

    Article  PubMed  CAS  Google Scholar 

  64. Obeso JA, Olanow CW, Nutt JG. Levodopa motor complications in Parkinson’s disease. Trends Neurosc 2000 Oct; 23(10) Suppl.: S2–7

    Article  CAS  Google Scholar 

  65. Olanow CW, Kordower JH, Freeman TB. Fetal nigral transplantation as a therapy for Parkinson’s disease. Trends Neurosci 1996 Mar; 19(3): 102–9

    Article  PubMed  CAS  Google Scholar 

  66. Helmuth L. Fetal cells help Parkinson’s patients. Science 1999 Oct; 286: 886–7

    Article  PubMed  CAS  Google Scholar 

  67. Freed CR, Breeze RE, Greene PE, et al. Double-blind placebo-controlled human fetal dopamine cell transplants in advanced Parkinson’s disease [abstract]. Abstr Soc Neurosci 1999 Oct; 199(25): 212

    Google Scholar 

  68. Fischbach GD, McKhann GM. Cell therapy for Parkinson’s disease. N Engl J Med 2001 Mar; 344(10): 763–5

    Article  PubMed  CAS  Google Scholar 

  69. Prospects for Parkinson disease [editorial]. Nat Med 2001 Apr; 7(4): 381

    Google Scholar 

  70. Abbott A. Trials offer way forward for Parkinson’s. Nature 2001 Mar; 410: 401

    Article  PubMed  CAS  Google Scholar 

  71. Freed CR, Breeze RE, Greene P. Reply to ‘Transplanted dopaminergic neurons: more or less?’ Nat Med 2001 May; 7(5): 512–3

    Article  Google Scholar 

  72. Takayama H, Ray J, Raymon HK. Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson’s disease. Nat Med 1995 Jan; 1(1): 53–8

    Article  PubMed  CAS  Google Scholar 

  73. Schierle GS, Hansson O, Leist M. Caspase inhibition reduces apoptosis and increases survival of nigral transplants. Nature Med 1999 Jan; 5(1): 97–100

    Article  PubMed  CAS  Google Scholar 

  74. Clarkson ED, La Rosa FG, Edwards-Prasad J, et al. Improvement of neurological deficits in 6-hydroxydopamine-lesioned rats after transplantation with allogeneic simian virus 40 large tumor antigen gene-induced immortalized dopamine cells. Proc Natl Acad Sci USA 1998 Feb; 95: 1256–70

    Article  Google Scholar 

  75. Brevig T, Holgersson J, Widner H. Xenotransplantation for CNS repair: immunological barriers and strategies to overcome them. Trends Neurosci 2000 Aug; 23(8): 337–44

    Article  PubMed  CAS  Google Scholar 

  76. Zawada WM, Cibeli JB, Choi PK, et al. Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats. Nature Med 1998 May; 4(5): 569–74

    Article  PubMed  CAS  Google Scholar 

  77. Pakzaban P, Deacon TW, Burns LH, et al. A novel mode of immunoprotection of neural xenotransplants: masking of donor major histocompatibilty complex class I enhances transplant survival in the central nervous system. Neuroscience 1995; 65: 983–96

    Article  PubMed  CAS  Google Scholar 

  78. Emerich DF, Winn SR, Christenson L, et al. A novel approach to neural transplantation in Parkinson’s disease: use of polymer encapsulated cell therapy. Neurosci Biobehav Rev 1992; 16: 437–47

    Article  PubMed  CAS  Google Scholar 

  79. Reynolds BA, Weiss D. Generation of neurons and astrocytes from isolated cells of the adult mammalian nervous system. Science 1992 Mar; 255: 1707–10

    Article  PubMed  CAS  Google Scholar 

  80. Azizi SA, Stokes D, Augelli BJ. Engraftment and migration of human bone marrow stromal cells implanted in to albino rats-similarities to astrocyte grafts. Proc Natl Acad Sci USA 1998 Mar; 95: 3908–13

    Article  PubMed  CAS  Google Scholar 

  81. Strauss E. Stem cells make brain cells. Science 2001 Mar; 291: 1689–90

    Article  PubMed  CAS  Google Scholar 

  82. Barinaga M. Fetal neuron grafts pave the way for stem cell therapies. Science 2000 Feb; 287: 1421–2

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

All funding has been provided by the US Army Institute for Chemical Defense. The author has no individual grants. There are no conflicts of interest. The author would like to thank his mentor and former employer Professor Curt R. Freed for training and input, Dr Kim B. Bjugstad for statistical analysis and Dr Daphne G. Albright for patience.

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Correspondence to Edward D. Clarkson.

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Clarkson, E.D. Fetal Tissue Transplantation for Patients with Parkinson’s Disease. Drugs & Aging 18, 773–785 (2001). https://doi.org/10.2165/00002512-200118100-00006

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