Sequential bilateral transplantation in Parkinson's disease: effects of the second graft.

Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.

[1]  R. McKay,et al.  Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats , 1998, Nature Neuroscience.

[2]  R. Hauser,et al.  Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson's disease , 1998, Movement disorders : official journal of the Movement Disorder Society.

[3]  J S Rakshi,et al.  Measuring the rate of progression and estimating the preclinical period of Parkinson’s disease with [18F]dopa PET , 1998, Journal of neurology, neurosurgery, and psychiatry.

[4]  Lars Björklund,et al.  Tirilazad Mesylate Increases Dopaminergic Neuronal Survival in thein OculoGrafting Model , 1997, Experimental Neurology.

[5]  O. Lindvall,et al.  Tirilazad Mesylate Improves Survival of Rat and Human Embryonic Mesencephalic Neuronsin Vitro , 1997, Experimental Neurology.

[6]  Björn Gustavii,et al.  Short‐ and long‐term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease , 1997, Annals of neurology.

[7]  S. DeKosky,et al.  Fetal grafting for Parkinson's disease: expression of immune markers in two patients with functional fetal nigral implants. , 1997, Cell transplantation.

[8]  Ole Isacson,et al.  Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease , 1997, Nature Medicine.

[9]  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.

[10]  Y. Samson,et al.  Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach. , 1996, Brain : a journal of neurology.

[11]  Vincent Frouin,et al.  Clinical correlates of {18F}fluorodopa uptake in five grafted Parkinsonian patients , 1995, Annals of neurology.

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

[13]  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.

[14]  P. Brundin,et al.  Lazaroids improve the survival of grafted rat embryonic dopamine neurons. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[15]  P. Brundin,et al.  Lazaroids improve the survival of cultured rat embryonic mesencephalic neurones. , 1994, Neuroreport.

[16]  Y. Samson,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. , 1994, Brain : a journal of neurology.

[17]  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.

[18]  A. Bjo¨rklund,et al.  Sequential intrastriatal grafting of allogeneic embryonic dopamine-rich neuronal tissue in adult rats: Will the second graft be rejected? , 1993, Neuroscience.

[19]  P. Brundin,et al.  Sequential Intracerebral Transplantation of Allogeneic and Syngeneic Fetal Dopamine-Rich Neuronal Tissue in Adult Rats: Will the First Graft be Rejected? , 1993, Cell transplantation.

[20]  A. Björklund,et al.  Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) , 1992, The New England journal of medicine.

[21]  Richard S. J. Frackowiak,et al.  Transplantation of fetal dopamine neurons in Parkinson's disease: PET {18F}6‐L‐fluorodopa studies in two patients with putaminal implants , 1992, Annals of neurology.

[22]  Richard S. J. Frackowiak,et al.  Transplantation of fetal dopamine neurons in Parkinson's disease: One‐year clinical and neurophysiological observations in two patients with putaminal implants , 1992, Annals of neurology.

[23]  C D Marsden,et al.  Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. , 1990, Science.

[24]  B J Hoffer,et al.  Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up. , 1989, Archives of neurology.

[25]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[26]  Marcel Leist,et al.  Caspase inhibition reduces apoptosis and increases survival of nigral transplants , 1999, Nature Medicine.

[27]  S. Rehncrona.  A critical review of the current status and possible developments in brain transplantation. , 1997, Advances and technical standards in neurosurgery.

[28]  D. Brooks,et al.  Core assessment program for intracerebral transplantations (CAPIT) , 1992, Movement disorders : official journal of the Movement Disorder Society.