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J02 Trident: investigating the safety and feasibility of fetal cell transplants in huntingtons disease
  1. Cheney JG Drew1,
  2. Feras Sharouf1,2,
  3. Elizabeth Randell1,
  4. Lucy Brookes-Howell1,
  5. Kim Smallman1,
  6. Bernadette Sewell3,
  7. Astrid Burrell4,
  8. Nigel Kirby1,
  9. Laura Mills1,
  10. Sophie Precious1,
  11. Philip Pallmann1,
  12. David Gillespie1,
  13. Kerry Hood1,
  14. Monica Busse1,
  15. William Gray1,2,
  16. Anne Rosser1,5,6
  1. 1Cardiff University, Cardiff, UK
  2. 2Cardiff and Vale University Health Board, University Hospital Wales, Cardiff, UK
  3. 3Swansea University
  4. 4Public and Patient Representative
  5. 5MRC Center for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
  6. 6Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK

Abstract

Background The relatively focal and specific loss of striatal medium spiny neurons in Huntington’s disease (HD) makes the disorder a suitable candidate for cell replacement therapy (CRT), a process involving the transplantation of donor cells to replace those lost due to disease. Whilst previous trials of CRT in HD have shown proof of principle, further investigation to demonstrate ongoing safety and efficacy is warranted.

Aim Assess the safety and feasibility of transplanting an increased number of human fetal striatal cells into the striatum of people with HD.

Methods TRIDENT (TRIal DEsigns for delivery of Novel Therapies in neurodegeneration) is an open label phase 1 trial using a Trial Within a Cohort (TWiC) design. A minimum of 18 participants will be enrolled in the study observational cohort, and up to five eligible participants will be randomly selected to undergo transplantation of 12-22 million fetal cells in a dose escalation paradigm. Independent reviewers will assess safety outcomes (lack of significant infection, bleeding or new neurological deficit) four weeks after surgery, and ongoing safety will be established before conducting each subsequent surgery. All participants will undergo detailed clinical and functional assessment at baseline, 6 and 12 months. Surgery will be performed one month after baseline, and transplant participants will undergo regular clinical follow-up for at least 12 months.

Results 20 participants have been recruited to the observational cohort. The first transplant surgery is scheduled for July 2021.

Conclusion The data collected in TRIDENT will; 1) enable assessment of the safety and feasibility of fetal cell transplants; 2) inform trial designs for complex intracranial interventions in a range of neurodegenerative conditions and 3) facilitate the development of stable surgical pipelines for delivery of future stem cell trials.

  • cell replacement
  • transplant
  • safety
  • feasibility

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