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59. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease

Author

Mendez, I, Sanchez-Pernaute, R, Cooper, O, Viñuela, A, Ferrari, D, Björklund, L, Dagher, A, Isacson, O, Mendez, I, Sanchez-Pernaute, R, Cooper, O, Viñuela, A, Ferrari, D, Björklund, L, Dagher, A, and Isacson, O

Abstract

We report the first post-mortem analysis of two patients with Parkinson's disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive 18F-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (n = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type that provides specific dopaminergic innervation to the most affected striatal regions in the parkinsonian brain. Such transplants were able to densely reinnervate the host putamen with new dopamine fibres. The patients received only 6 months of standard immune suppression, yet by post-mortem analysis 3-4 years after surgery the transplants appeared only mildly immunogenic to the host brain, by analysis of microglial CD45 and CD68 markers. This study demonstrates that, using these methods, dopamine neuronal replacement cell therapy can be beneficial for patients with advanced disease, and that changing technical approaches could have a favourable impact on efficacy and adverse events following neural transplantation. © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved

Published
2005

66. Impact of genomics on drug discovery and clinical medicine.

Author

UCL - MD/FSIO - Département de physiologie et pharmacologie, UCL - (SLuc) Service de neurologie, Emilien, G, Ponchon, M., Caldas, C, Isacson, O, Maloteaux, Jean-Marie, UCL - MD/FSIO - Département de physiologie et pharmacologie, UCL - (SLuc) Service de neurologie, Emilien, G, Ponchon, M., Caldas, C, Isacson, O, and Maloteaux, Jean-Marie

Abstract

Genomics, particularly high-throughput sequencing and characterization of expressed human genes, has created new opportunities for drug discovery. Knowledge of all the human genes and their functions may allow effective preventive measures, and change drug research strategy and drug discovery development processes. Pharmacogenomics is the application of genomic technologies such as gene sequencing, statistical genetics, and gene expression analysis to drugs in clinical development and on the market. It applies the large-scale systematic approaches of genomics to speed the discovery of drug response markers, whether they act at the level of the drug target, drug metabolism, or disease pathways. The potential implication of genomics and pharmacogenomics in clinical research and clinical medicine is that disease could be treated according to genetic and specific individual markers, selecting medications and dosages that are optimized for individual patients. The possibility of defining patient populations genetically may improve outcomes by predicting individual responses to drugs, and could improve safety and efficacy in therapeutic areas such as neuropsychiatry, cardiovascular medicine, endocrinology (diabetes and obesity) and oncology. Ethical questions need to be addressed and guidelines established for the use of genomics in clinical research and clinical medicine. Significant achievements are possible with an interdisciplinary approach that includes genetic, technological and therapeutic measures.

Published
2000

74. Transplantation of embryonic porcine mesencephalic tissue in patients with PD

Author

Schumacher, J. M., primary, Ellias, S. A., additional, Palmer, E. P., additional, Kott, H. S., additional, Dinsmore, J., additional, Dempsey, P. K., additional, Fischman, A. J., additional, Thomas, C., additional, Feldman, R. G., additional, Kassissieh, S., additional, Raineri, R., additional, Manhart, C., additional, Penney, D., additional, Fink, J. S., additional, and Isacson, O., additional

Published
2000
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