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The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.

Barker, R. A., Mason, S. L., Harrower, T. P., Swain, R. A., Ho, A. ORCID: https://orcid.org/0000-0002-2581-126X, Sahakian, B. J., Mathur, R., Elneil, S., Thornton, S., Hurrelbrink, C., Armstrong, R. J., Tyers, P., Smith, E., Carpenter, A., Piccini, P., Tai, Y. F., Brooks, D. J., Pavese, N., Watts, C., Pickard, J. D. , Rosser, A. E. and Dunnett, S. B. (2013) The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease. Journal of neurology, neurosurgery, and psychiatry, 84 (6). pp. 657-665. ISSN 1468-330X

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To link to this item DOI: 10.1136/jnnp-2012-302441

Abstract/Summary

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3-10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the 'Core assessment program for intracerebral transplantations-HD' assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD.

Item Type:Article
Refereed:Yes
Divisions:Life Sciences > School of Psychology and Clinical Language Sciences > Department of Psychology
Life Sciences > School of Psychology and Clinical Language Sciences > Neuroscience
Life Sciences > School of Psychology and Clinical Language Sciences > Language and Cognition
Life Sciences > School of Psychology and Clinical Language Sciences > Psychopathology and Affective Neuroscience
Life Sciences > School of Psychology and Clinical Language Sciences > Nutrition and Health
ID Code:32446
Publisher:BMJ Publishing Group

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