Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery
Individuals with Parkinson’s disease (PD) suffer from motor and mental disturbances due to degeneration of dopaminergic and non-dopaminergic neuronal systems. Although they provide temporary symptom relief, current treatments fail to control motor and non-motor alterations or to arrest disease progr...
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2019-03-01
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doaj-8cdd4a35d2dc46d29f285bb8ced1eeb32020-11-25T03:01:43ZengSAGE PublishingCell Transplantation0963-68971555-38922019-03-012810.1177/0963689718820271Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after SurgeryI. Madrazo0O. Kopyov1M. A. Ávila-Rodríguez2F. Ostrosky3H. Carrasco4A. Kopyov5A. Avendaño-Estrada6F. Jiménez7E. Magallón8C. Zamorano9G. González10T. Valenzuela11R. Carrillo12F. Palma13R. Rivera14R. E. Franco-Bourland15G. Guízar-Sahagún16 Hospital General de México “Dr. Eduardo Liceaga”, Mexico City, Mexico Celavie Biosciences LLC, Oxnard, CA, USA Unidad Radiofarmacia-Ciclotron, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico Facultad de Psicología, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico Hospital Central Militar, Mexico City, Mexico Celavie Biosciences LLC, Oxnard, CA, USA Unidad Radiofarmacia-Ciclotron, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico Neuroscience Center, Hospital Angeles Pedregal, Mexico City, Mexico Neuroscience Center, Hospital Angeles Pedregal, Mexico City, Mexico Neuroscience Center, Hospital Angeles Pedregal, Mexico City, Mexico Facultad de Psicología, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico Neuroscience Center, Hospital Angeles Pedregal, Mexico City, Mexico Hospital Angeles Pedregal, Mexico City, Mexico Hospital Angeles Pedregal, Mexico City, Mexico Hospital Angeles Pedregal, Mexico City, Mexico Department of Biochemistry, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoIndividuals with Parkinson’s disease (PD) suffer from motor and mental disturbances due to degeneration of dopaminergic and non-dopaminergic neuronal systems. Although they provide temporary symptom relief, current treatments fail to control motor and non-motor alterations or to arrest disease progression. Aiming to explore safety and possible motor and neuropsychological benefits of a novel strategy to improve the PD condition, a case series study was designed for brain grafting of human neural progenitor cells (NPCs) to a group of eight patients with moderate PD. A NPC line, expressing Oct-4 and Sox-2, was manufactured and characterized. Using stereotactic surgery, NPC suspensions were bilaterally injected into patients’ dorsal putamina. Cyclosporine A was given for 10 days prior to surgery and continued for 1 month thereafter. Neurological, neuropsychological, and brain imaging evaluations were performed pre-operatively, 1, 2, and 4 years post-surgery. Seven of eight patients have completed 4-year follow-up. The procedure proved to be safe, with no immune responses against the transplant, and no adverse effects. One year after cell grafting, all but one of the seven patients completing the study showed various degrees of motor improvement, and five of them showed better response to medication. PET imaging showed a trend toward enhanced midbrain dopaminergic activity. By their 4-year evaluation, improvements somewhat decreased but remained better than at baseline. Neuropsychological changes were minor, if at all. The intervention appears to be safe. At 4 years post-transplantation we report that undifferentiated NPCs can be delivered safely by stereotaxis to both putamina of patients with PD without causing adverse effects. In 6/7 patients in OFF condition improvement in UPDRS III was observed. PET functional scans suggest enhanced putaminal dopaminergic neurotransmission that could correlate with improved motor function, and better response to L-DOPA. Patients’ neuropsychological scores were unaffected by grafting. Trial Registration: Fetal derived stem cells for Parkinson’s disease https://doi.org/10.1186/ISRCTN39104513Reg#ISRCTN39104513https://doi.org/10.1177/0963689718820271 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
I. Madrazo O. Kopyov M. A. Ávila-Rodríguez F. Ostrosky H. Carrasco A. Kopyov A. Avendaño-Estrada F. Jiménez E. Magallón C. Zamorano G. González T. Valenzuela R. Carrillo F. Palma R. Rivera R. E. Franco-Bourland G. Guízar-Sahagún |
spellingShingle |
I. Madrazo O. Kopyov M. A. Ávila-Rodríguez F. Ostrosky H. Carrasco A. Kopyov A. Avendaño-Estrada F. Jiménez E. Magallón C. Zamorano G. González T. Valenzuela R. Carrillo F. Palma R. Rivera R. E. Franco-Bourland G. Guízar-Sahagún Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery Cell Transplantation |
author_facet |
I. Madrazo O. Kopyov M. A. Ávila-Rodríguez F. Ostrosky H. Carrasco A. Kopyov A. Avendaño-Estrada F. Jiménez E. Magallón C. Zamorano G. González T. Valenzuela R. Carrillo F. Palma R. Rivera R. E. Franco-Bourland G. Guízar-Sahagún |
author_sort |
I. Madrazo |
title |
Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery |
title_short |
Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery |
title_full |
Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery |
title_fullStr |
Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery |
title_full_unstemmed |
Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery |
title_sort |
transplantation of human neural progenitor cells (npc) into putamina of parkinsonian patients: a case series study, safety and efficacy four years after surgery |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2019-03-01 |
description |
Individuals with Parkinson’s disease (PD) suffer from motor and mental disturbances due to degeneration of dopaminergic and non-dopaminergic neuronal systems. Although they provide temporary symptom relief, current treatments fail to control motor and non-motor alterations or to arrest disease progression. Aiming to explore safety and possible motor and neuropsychological benefits of a novel strategy to improve the PD condition, a case series study was designed for brain grafting of human neural progenitor cells (NPCs) to a group of eight patients with moderate PD. A NPC line, expressing Oct-4 and Sox-2, was manufactured and characterized. Using stereotactic surgery, NPC suspensions were bilaterally injected into patients’ dorsal putamina. Cyclosporine A was given for 10 days prior to surgery and continued for 1 month thereafter. Neurological, neuropsychological, and brain imaging evaluations were performed pre-operatively, 1, 2, and 4 years post-surgery. Seven of eight patients have completed 4-year follow-up. The procedure proved to be safe, with no immune responses against the transplant, and no adverse effects. One year after cell grafting, all but one of the seven patients completing the study showed various degrees of motor improvement, and five of them showed better response to medication. PET imaging showed a trend toward enhanced midbrain dopaminergic activity. By their 4-year evaluation, improvements somewhat decreased but remained better than at baseline. Neuropsychological changes were minor, if at all. The intervention appears to be safe. At 4 years post-transplantation we report that undifferentiated NPCs can be delivered safely by stereotaxis to both putamina of patients with PD without causing adverse effects. In 6/7 patients in OFF condition improvement in UPDRS III was observed. PET functional scans suggest enhanced putaminal dopaminergic neurotransmission that could correlate with improved motor function, and better response to L-DOPA. Patients’ neuropsychological scores were unaffected by grafting. Trial Registration: Fetal derived stem cells for Parkinson’s disease https://doi.org/10.1186/ISRCTN39104513Reg#ISRCTN39104513 |
url |
https://doi.org/10.1177/0963689718820271 |
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