Robust graft survival and normalized dopaminergic innervation do not obligate recovery in a Parkinson disease patient

The main goal of dopamine cell replacement therapy in Parkinson disease (PD) is to provide clinical benefit mediated by graft survival with nigrostriatal reinnervation. We report a dichotomy between graft structure and clinical function in a patient dying 16 years following fetal nigral grafting.

[1]  C. Olanow,et al.  Fetal grafts for Parkinson’s disease: Decades in the making , 2016, Proceedings of the National Academy of Sciences.

[2]  A. Björklund,et al.  Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain , 2016, Proceedings of the National Academy of Sciences.

[3]  J. Kordower,et al.  Abnormal alpha-synuclein reduces nigral voltage-dependent anion channel 1 in sporadic and experimental Parkinson's disease , 2014, Neurobiology of Disease.

[4]  C. Adler,et al.  Disease duration and the integrity of the nigrostriatal system in Parkinson's disease. , 2013, Brain : a journal of neurology.

[5]  J. Kordower,et al.  Cell Therapy for Parkinson's Disease: What Next? , 2013, Movement disorders : official journal of the Movement Disorder Society.

[6]  C. Olanow,et al.  Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion‐Like Disorder? , 2013, Movement disorders : official journal of the Movement Disorder Society.

[7]  J. Kordower,et al.  Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease. , 2012, Brain : a journal of neurology.

[8]  A. Björklund,et al.  Characterization of Lewy body pathology in 12‐ and 16‐year‐old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[9]  J. Kordower,et al.  Lewy body pathology in fetal grafts , 2010, Annals of the New York Academy of Sciences.

[10]  J. Kordower,et al.  Propagation of host disease to grafted neurons: Accumulating evidence , 2009, Experimental Neurology.

[11]  S. Prusiner,et al.  Is Parkinson's disease a prion disorder? , 2009, Proceedings of the National Academy of Sciences.

[12]  J. Gracies,et al.  Clinical pattern and risk factors for dyskinesias following fetal nigral transplantation in Parkinson's disease: A double blind video‐based analysis , 2009, Movement disorders : official journal of the Movement Disorder Society.

[13]  Elena Urrestarazu,et al.  Beta activity in the subthalamic nucleus during sleep in patients with Parkinson's disease , 2009, Movement disorders : official journal of the Movement Disorder Society.

[14]  R. Hauser,et al.  Transplanted dopaminergic neurons develop PD pathologic changes: A second case report , 2008, Movement disorders : official journal of the Movement Disorder Society.

[15]  R. Hauser,et al.  Lewy body–like pathology in long-term embryonic nigral transplants in Parkinson's disease , 2008, Nature Medicine.

[16]  Elisabet Englund,et al.  Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation , 2008, Nature Medicine.

[17]  J. Kordower,et al.  Age-associated increases of α-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson's disease? , 2007, Neurobiology of Disease.

[18]  P. Riederer,et al.  Evidence for specific phases in the development of human neuromelanin , 2006, Journal of Neural Transmission.

[19]  A. Dagher,et al.  Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease. , 2005, Brain : a journal of neurology.

[20]  Vesna Sossi,et al.  A double‐blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease , 2003, Annals of neurology.

[21]  C. Olanow,et al.  Transplantation of embryonic dopamine neurons for severe Parkinson's disease. , 2001, The New England journal of medicine.

[22]  Patrick R Hof,et al.  Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach , 2000, Journal of Chemical Neuroanatomy.

[23]  E. Mufson,et al.  Functional fetal nigral grafts in a patient with Parkinson's disease: Chemoanatomic, ultrastructural, and metabolic studies , 1996, The Journal of comparative neurology.

[24]  C. Olanow,et al.  Fetal nigral transplantation as a therapy for Parkinson's disease , 1996, Trends in Neurosciences.

[25]  F. Vingerhoets,et al.  Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease , 1995, Annals of neurology.

[26]  P R Sanberg,et al.  Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease. , 1995, The New England journal of medicine.

[27]  Richard S. J. Frackowiak,et al.  Evidence for long‐term survival and function of dopaminergic grafts in progressive Parkinson's disease , 1994, Annals of neurology.

[28]  H J Gundersen,et al.  The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson's disease estimated with an unbiased stereological method. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[29]  H. Gundersen,et al.  Unbiased stereological estimation of the number of neurons in the human hippocampus , 1990, The Journal of comparative neurology.

[30]  R. Bakay,et al.  Biochemical and Behavioral Correction of MPTP Parkinson‐like Syndrome by Fetal Cell Transplantation a , 1987, Annals of the New York Academy of Sciences.

[31]  S. Haber,et al.  FETAL NEURONAL GRAFTS IN MONKEYS GIVEN METHYLPHENYLTETRAHYDROPYRIDINE , 1986, The Lancet.

[32]  W. Freed,et al.  Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: Long‐term behavioral, biochemical, and histochemical studies , 1980, Annals of neurology.

[33]  A. Bjo¨rklund,et al.  Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants , 1979, Brain Research.

[34]  B J Hoffer,et al.  Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. , 1979, Science.

[35]  A. Bjo¨rklund,et al.  Transplantation of central and peripheral monoamine neurons to the adult rat brain: Techniques and conditions for survival , 1976, Brain Research.

[36]  I. Chalmers.  Letter: Obstetric Delivery Today. , 1976, Lancet.

[37]  Jeffrey H Kordower,et al.  Neuropathology in transplants in Parkinson's disease: implications for disease pathogenesis and the future of cell therapy. , 2012, Progress in brain research.