Histological analysis of fetal dopamine cell suspension grafts in two patients with Parkinson's disease gives promising results
Deniz Kirik,Anders Björklund +1 more
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The postmortem analysis of brains from two patients with Parkinson's disease who had received grafts of brain tissue dissected from the developing ventral mesencephalic region, obtained from 6- to 9-week-old aborted fetuses, which is known to contain the appropriate type of dopamine neurones lost in these patients as a result of their disease.Abstract:
In this issue of Brain (pages 1498–1510), Mendez and collaborators report the postmortem analysis of brains from two patients with Parkinson's disease who had received grafts of brain tissue dissected from the developing ventral mesencephalic region, obtained from 6- to 9-week-old aborted fetuses, which is known to contain the appropriate type of dopamine neurones lost in these patients as a result of their disease. The most important aspect of this report is the fact that this is the first time we have been able to evaluate the outcome of so-called cell suspension grafts, a more refined cell preparation technique than has been used in the previously reported autopsy cases.
Since 1987, when the first clinical neural transplantation trials were initiated, some 350 Parkinson's disease patients have received intrastriatal grafts of human fetal mesencephalic tissue (Lindvall and Bjorklund, 2004; Winkler et al ., 2005). However, there has so far been no attempt to standardize the way in which the transplantation is carried out at different centres. Almost all aspects of tissue handling and storage, and of graft preparation, have differed from one centre to another (Winkler et al ., 2005). In several open-label trials, such as those performed in Lund, Paris and Halifax, grafts prepared as cell suspensions have been used, whereas other centres …read more
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Re-examining the ontogeny of substantia nigra dopamine neurons.
Monte A. Gates,Eduardo Miguel Torres,Anna White,Rosemary A. Fricker-Gates,Stephen B. Dunnett +4 more
TL;DR: Describing the ontogeny of substantia nigra pars compacta dopamine neurons in rats commonly used as a source of donor tissue for experimental cell transplantation in animal models of Parkinson's disease reveals that the vast majority (perhaps 80%) of SNc dopamine neurons are probably born on E12 in Sprague‐Dawley rats.
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Cellular therapy and induced neuronal replacement for Huntington's disease.
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Aggregopathy in Neurodegenerative Diseases: Mechanisms and Therapeutic Implication
TL;DR: The current understanding of aggregate formation and toxicity in neurodegenerative diseases with an emphasis on Parkinson’s disease is summarized and current treatment strategies in these diseases targeting aggregation formation and concurrent neuronal cell death are discussed.
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Intracerebral transplantation of genetically engineered cells for Parkinson's disease: toward clinical application.
TL;DR: Genetically engineered cell transplantation for animal models of PD, including catecholamine/neurotrophic factor-secreting cell transplation with or without encapsulation, as performed in the laboratories, and their potential future as clinical applications are described with recent clinical studies in this field.
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Cell transplantation for Huntington's disease Should we continue?
TL;DR: The potential for cell transplantation in Huntington's disease is greater than has yet been realised, and remains a therapeutic strategy worthy of investigation and pursuit.
References
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Journal ArticleDOI
Transplantation of embryonic dopamine neurons for severe Parkinson's disease.
Curt R. Freed,Paul Greene,Robert E. Breeze,Wei-Yann Tsai,William DuMouchel,Richard Kao,Sandra Dillon,Howard Winfield,Sharon Culver,John Q. Trojanowski,David Eidelberg,Stanley Fahn +11 more
TL;DR: After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa.
Journal ArticleDOI
A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease†
C. Warren Olanow,Christopher G. Goetz,Jeffrey H. Kordower,A. Jon Stoessl,Vesna Sossi,Mitchell F. Brin,Kathleen M. Shannon,G. Michael Nauert,Daniel P. Perl,James Godbold,Thomas B. Freeman +10 more
TL;DR: Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on results, and Stratification based on disease severity showed a treatment effect in milder patients.
Journal ArticleDOI
Cell Therapy in Parkinson's Disease
Olle Lindvall,Anders Björklund +1 more
TL;DR: The clinical studies with intrastriatal transplants of fetal mesencephalic tissue in Parkinson’s disease patients have provided proof-of-principle for the cell replacement strategy in this disorder, but several scientific issues need to be addressed before stem cell-based therapies can be tested in PD patients.
Journal ArticleDOI
Cell transplantation in Parkinson's disease: how can we make it work?
TL;DR: The problems raised by the NIH-sponsored trials are discussed and several shortcomings that might explain the overall poor outcome are pointed to.