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Research paper
The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease
  1. Roger A Barker1,2,
  2. Sarah L Mason1,
  3. Timothy P Harrower1,2,
  4. Rachel A Swain1,
  5. Aileen K Ho1,
  6. Barbara J Sahakian4,
  7. Raj Mathur,
  8. Sohier Elneil5,
  9. Steven Thornton5,
  10. Carrie Hurrelbrink1,
  11. Richard J Armstrong1,
  12. Pam Tyers1,
  13. Emma Smith1,
  14. Adrian Carpenter3,
  15. Paola Piccini6,
  16. Yen F Tai6,
  17. David J Brooks6,
  18. Nicola Pavese6,
  19. Colin Watts1,3,
  20. John D Pickard1,3,
  21. Anne E Rosser1,7,
  22. Stephen B Dunnett1,7,
  23. the NEST-UK collaboration
  1. 1Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
  2. 2Department of Clinical Neuroscience, University of Cambridge Medical School, Addenbrooke's Hospital, Cambridge UK
  3. 3Department of Neurosurgery, University of Cambridge Medical School, Addenbrooke's Hospital, Cambridge UK
  4. 4Department of Psychiatry, University of Cambridge Medical School, Addenbrooke's Hospital, Cambridge UK
  5. 5Department of Obstetrics and Gynaecology, University of Cambridge Medical School, Addenbrooke's Hospital, Cambridge, UK
  6. 6Centre for Neuroscience, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK
  7. 7Brain Repair Group, School of Biosciences and Medicine, Cardiff University, Wales, UK
  1. Correspondence to Dr Roger Barker, Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Cambridge CB2 0PY, UK; rab46{at}cam.ac.uk

Abstract

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.

  • Huntington's

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