Intracranial Stem Cell-Based Transplantation: Reconsidering the Ethics of Phase 1 Clinical Trials in Light of Irreversible Interventions in the Brain

AJOB Neuroscience

Volumn 3, Issue 2, 2012, Pages 3-13

  Hess, Pascale ^a  

^a DALHOUSIE UNIVERSITY   (Canada)

Author keywords

brain; human subjects; morality ethics; transplantation

Indexed keywords

EID: 84860320282     PISSN: 21507740     EISSN: 21507759     Source Type: Journal    
DOI: 10.1080/21507740.2012.663057     Document Type: Article

References (68)

1. Anderson, J. A. and Kimmelman, J. 2010. Extending clinical equipoise to phase 1 trials involving patients: Unresolved problems. Kennedy Institute of Ethics Journal, 20(1): 75-98.
2. Bachoud-Lévi, A. C., Gaura, V.Brugières, P. 2006. Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: A long-term follow-up study. Lancet Neurology, 5(4): 303-309.
3. Bezard, E. 2006. A call for clinically driven experimental design in assessing neuroprotection in experimental Parkinsonism. Behavioural Pharmacology, 17(5-6): 379-382.
4. Boucherie, C. and Hermans, E. 2009. Adult stem cell therapies for neurological disorders: Benefits beyond neuronal replacement?. Journal of Neuroscience Research, 87(7): 1509-1521.
5. Carter, A., Bartlett, P. and Hall, W. 2009. Scare-mongering and the anticipatory ethics of experimental technologies. American Journal of Bioethics, 9(5): 47-48.
6. Council for International Organizations of Medical Sciences. 2002. International ethical guidelines for biomedical research involving human subjects, Geneva, Switzerland: CIOMS.
7. Daugherty, C., Ratain, M. J.Grochowski, E. 1995. Perceptions of cancer patients and their physicians involved in phase I trials. Journal of Clinical Oncology, 13(5): 1062-1072.
8. Daugherty, C. K., Ratain, M. J.Minami, H. 1998. Study of cohort-specific consent and patient control in phase I cancer trials. Journal of Clinical Oncology, 16(7): 2305-2301.
9. Dunnet, B. and Rosser, A. E. 2007. Cell transplantation for Huntington's disease. Should we continue?. Brain Research Bulletin, 72: 132-147.
10. Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. 1995. Guidance for industry content and format of investigational new drug applications (INDs) for phase 1 studies of drugs, including well-characterized, therapeutic, biotechnology-derived products, Rockville, MD: FDA.
11. Food and Drug Administration. 1997. International Conference on Harmonization; Guidance on general considerations for clinical trials. Federal Register, 62: 66113-66119.
12. Freed, C. R., Greene, P. E.Breeze, R. E. 2001. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. New England Journal of Medicine, 344(10): 710-719.
13. Goebel, H. H. and Wisniewski, K. E. 2004. Current state of clinical and morphological features in human NCL. Brain Pathology, 14: 61-69.
14. Grunwell, J., Illes, J. and Karkazis, K. 2008. Advancing neurodegenerative medicine: A call for expanded collaboration between scientists and ethicists. Neuroethics, 2(1): 13-20.
15. Guillaume, D. J. and Zhang, S. C. 2008. Human embryonic stem cells: A potential source of transplantable neural progenitor cells. Neurosurgical Focus, 24(3-4): 1-7.
16. Guillaume, D. J., Huhn, S. L.Selden, N. R. 2008. Cellular therapy for childhood neurodegenerative disease. Part I: Rationale and preclinical studies. Neurosurgical Focus, 24(3-4): E22
17. Henderson, G. E., Churchill, L. R.Davis, A. M. 2007. Clinical trials and medical care: defining the therapeutic misconception. PLoS Medicine, 4(11): e324
18. Horstmann, E., McCabe, M. S.Grochow, L. 2005. Risks and benefits of phase 1 oncology trials, 1991 through 2002. New England Journal of Medicine, 352(9): 895-904.
19. Joffe, S. and Miller, F. G. 2008. Bench to bedside: Mapping the moral terrain of clinical research. Hastings Center Report, 38(2): 30-42.
20. Kim, S. Y., Appelbaum, P. S.Jeste, D. V. 2004. Proxy and surrogate consent in geriatric neuropsychiatric research: Update and recommendations. American Journal of Psychiatry, 161(5): 797-806.
21. Kimmelman, J. 2007. The therapeutic misconception at 25: Treatment, research, and confusion. Hastings Center Report, 37(6): 36-42.
22. Kimmelman, J. 2009. Gene transfer and the ethics of first-in-human experiments: Lost in translation, New York, NY: Cambridge University Press.
23. Kimmelman, J., London, A. J.Ravina, B. 2009. Launching invasive, first-in-human trials against Parkinson's disease: Ethical considerations. Movement Disorders, 24(13): 1893-1901.
24. King, N. M. 2000. Defining and describing benefit appropriately in clinical trials. Journal of Law, Medicine and Ethics, 28(4): 332-343.
25. Kopelman, L. M. and Murphy, T. F. 2004. Ethical concerns about federal approval of risky pediatric studies. Pediatrics, 113(6): 1783-1789.
26. Lindvall, O. and Björklund, A. 2004. Cell therapy in Parkinson's disease. NeuroRx, 4: 382-393.
27. Lindvall, O. and Kokaia, Z. 2010. Stem cells in human neurodegenerative disorders-Time for clinical translation?. Journal of Clinical Investigation, 120(1): 29-40.
28. Lowenstein, P. R. 2008. Clinical trials in gene therapy: ethics of informed consent and the future of experimental medicine. Current Opinion in Molecular Therapeutics, 10(5): 428-430.
29. Magnus, D. 2010. Translating stem cell research: Challenges at the research frontier. Journal of Law, Medicine, and Ethics, 38(2): 267-276.
30. Martin, R. A. and Robert, J. S. 2007. Is risky pediatric research without prospect of direct benefit ever justified?. American Journal of Bioethics, 7(3): 12-15.
31. Master, Z., McLeod, M. and Mendez, I. 2007. Benefits, risks and ethical considerations in translation of stem cell research to clinical applications in Parkinson's disease. Journal of Medical Ethics, 33(3): 169-173.
32. Mathews, D. J., Sugarman, J.Bok, H. 2008. Cell-based interventions for neurologic conditions: ethical challenges for early human trials. Neurology, 71(4): 288-293.
33. Miller, M. 2000. Phase I cancer trials. A collusion of misunderstanding. Hastings Center Report, 4: 34-43.
34. Miller, P. B. and Weijer, C. 2007. Equipoise and the duty of care in clinical research: A philosophical response to our critics. Journal of Medicine and Philosophy, 32(2): 117-133.
35. National Institutes of Health. 1998. Policy and guidelines on the inclusion of children as participants in research involving human subjects, Bethesda, MD: NIH.
36. Neuralstem. 2009. Neuralstem receives FDA approval to commence first ALS stem cell trial Available at: http://www.neuralstem.com/index.asp?pgid = 42 (accessed November 26, 2010)
37. Nurgat, Z. A., Craig, W.Campbell, N. C. 2005. Patient motivations surrounding participation in phase I and phase II clinical trials of cancer chemotherapy. British Journal of Cancer, 92(6): 1001-1005.
38. Olanow, C. W., Goetz, C. G.Kordower, J. H. 2003. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Annals of Neurology, 54(3): 403-414.
39. Oberman, M. and Frader, J. 2003. Dying children and medical research: access to clinical trials as benefit and burden. American Journal of Law and Medicine, 29(2-3): 301-317.
40. Patoine, B. 2009. Stem cell treatment for brain disorder appears safe, but efficacy still unknown. Available at: http://www.dana.org/news/features/detail.aspx?id = 22836
41. Regenberg, A., Mathews, D. J.Blass, D. M. 2009. The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions. Journal of Cerebral Blood Flow and Metabolism, 29(1): 1-9.
42. Resnik, D. B. and Miller, F. 2010. The ethics of sham surgery on research subjects with cognitive impairments that affect decision-making capacity. Contemporary Clinical Trials, 31(5): 407-410.
43. Ross, L. 2006. Phase I research and the meaning of direct benefit. Journal of Pediatrics, 149(1 SUPPL.): S20-S24.
44. Shah, S., Whittle, A.Wilfond, B. 2004. How do institutional review boards apply the federal risk and benefit standards for pediatric research?. Journal of the American Medical Association, 291(4): 476-482.
45. Scheffer, I. E., Baraitser, M.Wilson, J. 1991. Pelizaeus- Merzbacher disease: Classical or connatal?. Neuropediatrics, 22(2): 71-78.
46. Schwartz, P. H. and Kalichman, M. W. 2009. Ethical challenges to cell-based interventions for the central nervous system: some recommendations for clinical trials and practice. American Journal of Bioethics, 9(5): 41-43.
47. Selden, N. R., Guillaume, D. J.Steiner, R. D. 2008. Cellular therapy for childhood neurodegenerative disease. Part II: Clinical trial design and implementation. Neurosurgical Focus, 24(3-4): E23
48. Selden, N. R., Guillaume, D. J.Steiner, R. D. 2008. Cellular therapy for childhood neurodegenerative disease. Part II: Clinical trial design and implementation. Neurosurgical Focus, 24(3-4): E23
49. Sondhi, D., Hackett, N. R.Peterson, D. A. 2007. Enhanced survival of the LINCL mouse following CLN2 gene transfer using the rh10 rhesus macaque-derived adeno-associated virus vector. Molecular Therapy, 15(3): 481-491.
50. StemCells, Inc. 2009. StemCells, Inc. announces positive phase 1 Batten trial results. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle&ID=1297008&high light= (accessed November 26, 2010)
51. StemCells, Inc. 2010a. StemCells, Inc. announces first human neural stem cell transplant in landmark myelination disorder trial. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle_print&ID=1386091&highlight = (accessed November 26, 2010)
52. StemCells, Inc. 2010b. StemCells, Inc. reports progress in myelination disorder trial. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle&ID=1480189 &highlight = (accessed November 26, 2010)
53. StemCells, Inc. 2010c. StemCells, Inc. plans to advance to second clinical trial in Batten disease. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle&ID = 1415661&highlight = (accessed November 26, 2010)
54. Stemcells, Inc. 2010d. StemCells, Inc. advances to second clinical trial in Batten disease. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle&ID=1488590 &highlight= (accessed November 26, 2010)
55. StemCells, Inc. 2010e. StemCells, Inc.'s phase I Batten trial data featured at American Association of Neurological Surgeons Annual Meeting. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle&ID=1421146&high light=
56. StemCells, Inc. 2011a. StemCells, Inc. discontinues Batten disease program. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle&ID=1488590&highlight= (accessed April 2, 2011)
57. StemCells, Inc. 2011b. StemCells, Inc. completes dosing in second trial of HuCNS-SC(R) neural stem cells. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p= irol-newsArticle&ID=1530091&highlight= (accessed May 2, 2011)
58. StemCells, Inc. 2012a. StemCells, Inc's Milestone Clinical Trial in Pelizaeus-Merzbacher Disease Shows Evidence of Myelination Following Human Neural Stem Cell Transplantation. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-newsArticle&ID=1678880&highlight= (accessed April 2, 2012)
59. StemCells, Inc. 2012b. StemCells, Inc. to Discuss Pelizaeus-Merzbacher Disease Phase I Clinical Trial Results Conference Call. Available at: http://investor.stemcellsinc.com/phoenix.zhtml?p=irol-eventDetails&c=86230&eventID=4746221 (accessed April 2, 2012)
60. Tamaki, S. J., Jacobs, Y.Dohse, M. 2009. Neuroprotection of host cells by human central nervous system stem cells in a mouse model of infantile neuronal ceroid lipofuscinosis. Cell Stem Cell, 5(3): 310-319.
61. Trapp, B. D. 2008. Rescue of congenital hypomyelination by progenitor cell transplantation. Cell Stem Cell, 2(6): 519-520.
62. Uchida, N. 2008. Translating human CNS stem cells to clinic: Neuroprotection, Philadelphia: 6th ISSCR Annual Meeting. June 11-14
63. Valeo, T. 2006. Clinical trials for neural stem cells approved for Batten disease. Neurology Today, 6(28): 1-12.
64. Weijer, C. and Miller, P. B. 2004. When are research risks reasonable in relation to anticipated benefits?. Nature Medicine, 10(6): 570-573.
65. Weijer, C. and Miller, P. B. 2007. Refuting the net risks test: A response to Wendler and Miller's Assessing research risks systematically. Journal of Medicine and Ethics, 33(8): 487-490.
66. Windrem, S. C., Schanz, S. J.Guo, M. 2008. Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse. Cell Stem Cell, 2(6): 553-565.
67. Worgall, S., Sondhi, D.Hackett, N. R. 2008. Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Human Gene Therapy, 19(5): 463-474.
68. World Medical Association. 2008. WMA declaration of Helsinki-Ethical principles for medical research involving human subjects 2008, Seoul: 59th WMA General Assembly. October