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Resolving Ethical Issues in Stem Cell Clinical Trials: The Example of Parkinson Disease

Published online by Cambridge University Press:  01 January 2021

Extract

Stem cells derived from pluripotent cells offer the hope of new treatments for diseases for which current therapy is inadequate. Clinical trials are essential in developing effective and safe stem cell therapies and fulfilling this promise. However, such clinical trials raise ethical issues that are more complex than those raised in clinical trials using drugs, cord blood stem cells, or adult stem cells. Several clinical trials are now being carried out with stem cells derived from pluripotent cells, and many more can be expected in light of the rapid scientific progress in the field.

Degenerative neurological diseases are desirable targets for stem cell clinical trials. The FDA has approved Phase 1 clinical trials of neural stem cell transplantation for Batten Disease, Pelizaeus-Merzbacher Disease, and spinal cord injury. In Parkinson Disease (PD), stem cell transplantation could correct the primary pathophysiological defect — inadequate levels of the neurotransmitter dopamine. Current treatment is unsatisfactory in late-stage PD.

Type
Symposium
Copyright
Copyright © American Society of Law, Medicine and Ethics 2010

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References

Soldner, F. and Hockemeyer, D. et al., “Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors,” Cell 136, no. 5 (2009): 964–77.CrossRefGoogle Scholar
Dresser, R., When Science Offers Salvation: Patient Advocacy and Research Ethics (New York: Oxford University Press, 2001).Google Scholar
Amariglio, N. and Hirshberg, A. et al., “Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient,” PLoS Medicine 6, no. 2 (2009): e1000029.CrossRefGoogle Scholar
Hyun, I. and Lindvall, O. et al., “New Isscr Guidelines Underscore Major Principles for Responsible Translational Stem Cell Research,” Cell Stem Cell 3, no. 6 (2008): 607–9; Lo, B., Kriegstein, A., and Grady, D., “Clinical Trials in Stem Cell Transplantation: Guidelines for Scientific and Ethical Review,” Clinical Trials 5, no. 5 (2008): 517–22; Mathews, D. J. and Sugarman, J. et al., “Cell-Based Interventions for Neurologic Conditions: Ethical Challenges for Early Human Trials,” Neurology 71, no. 4 (2008): 288293.CrossRefGoogle Scholar
Poewe, W., “Treatments for Parkinson Disease – Past Achievements and Current Clinical Needs,” Neurology 72, no. 7 Supp. (2009): S65S73.CrossRefGoogle Scholar
Benabid, A. L., Chabardes, S., Mitrofanis, J., and Pollak, P., “Deep Brain Stimulation of the Subthalamic Nucleus for the Treatment of Parkinson's Disease,” Lancet Neurology 8, no. 1 (2009): 6781; Weaver, F. M. and Follett, K. et al., “Bilateral Deep Brain Stimulation vs. Best Medical Therapy for Patients with Advanced Parkinson Disease: A Randomized Controlled Trial,” JAMA 301, no. 1 (2009): 6373.CrossRefGoogle Scholar
Freed, C. R. and Greene, P. E. et al., “Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease,” N. Engl. J. Med. 344, no. 10 (2001): 710–9; Olanow, C. W., Goetz, C. G. et al., “A Double-Blind Controlled Trial of Bilateral Fetal Nigral Transplantation in Parkinson's Disease,” Annals of Neurology 54, no. 3 (2003): 403–14.CrossRefGoogle Scholar
Braak, H. and Del Tredici, K., “Assessing Fetal Nerve Cell Grafts in Parkinson's Disease,” Nature Medicine 14, no. 5 (2008): 483485; Kordower, J. H. and Chu, Y. et al., “Lewy Body-Like Pathology in Long-Term Embryonic Nigral Transplants in Parkinson's Disease,” Nature Medicine 14, no. 5 (2008): 504506; Li, J. Y. and Englund, E. et al., “Lewy Bodies in Grafted Neurons in Subjects with Parkinson's Disease Suggest Host-to-Graft Disease Propagation,” Nature Medicine 14, no. 5 (2008): 501503; Mendez, I. and Vinuela, A. et al., “Dopamine Neurons Implanted into People with Parkinson's Disease Survive without Pathology for 14 Years,” Nature Medicine 14, no. 5 (2008): 507509.CrossRefGoogle Scholar
Bodeen, C. and Zagier, A. S., “China Offers Unproven Medical Treatments,” San Francisco Chronicle, January 6 2008, A17; Enserink, M., “Selling the Stem Cell Dream,” Science 313, no. 5784 (2006): 160163; Padma, T. V., “Unchecked by Guidelines, Indian Stem Cell Scientists Rush Ahead,” Nature Medicine 12, no. 1 (2006): 4.Google Scholar
Dobkin, B. H., Curt, A., and Guest, J., “Cellular Transplants in China: Observational Study from the Largest Human Experiment in Chronic Spinal Cord Injury,” Neurorehabilitation & Neural Repair 20, no. 1 (2006): 513.CrossRefGoogle Scholar
See Freed, , supra at note 7.Google Scholar
Council for International Organizations of Medical Sciences, “Cioms International Ethical Guidelines for Biomedical Research Involving Human Subjects, Revised Draft,” available at <http://www.cioms.ch/frame_guidelines_january_2002.htm> (last visited April 5, 2010); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Biomedical and Behavioral Research (Washington, D.C.: U.S. Government Printing Office, 1979); World Medical Association, “Declaration of Helsinki,” avaialable at <http://www.wma.net/e/ethicsunit/helsinki.htm> (last visited April 5, 2010).+(last+visited+April+5,+2010);+National+Commission+for+the+Protection+of+Human+Subjects+of+Biomedical+and+Behavioral+Research,+The+Belmont+Report:+Ethical+Principles+and+Guidelines+for+the+Protection+of+Human+Subjects+of+Biomedical+and+Behavioral+Research+(Washington,+D.C.:+U.S.+Government+Printing+Office,+1979);+World+Medical+Association,+“Declaration+of+Helsinki,”+avaialable+at++(last+visited+April+5,+2010).>Google Scholar
Protection of Human Subjects, 45 Cfr 46 (2005), available at <http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm> (last visited April 5, 2010).+(last+visited+April+5,+2010).>Google Scholar
Lo, B., Ethical Dilemmas in Clinical Research: A Practical Guide, (Philadelphia: Lippincott Williams & Wilkins, 2009).Google Scholar
Joffe, S. and Cook, E. F. et al., “Quality of Informed Consent in Cancer Clinical Trials: A Cross-Sectional Survey,” Lancet 358, no. 9295 (2001): 17721777.CrossRefGoogle Scholar
Appelbaum, P. S. and Lidz, C. W., “The Therapeutic Misconception,” in Emanuel, E. J. et al., ed., The Oxford Textbook of Clinical Research Ethics (New York: Oxford University Press, 2008): 633644; Lidz, C. W., Appelbaum, P. S., Grisso, T., and Renaud, M., “Therapeutic Misconception and the Appreciation of Risks in Clinical Trials,” Social Science Medicine 58, no. 9 (2004): 16891697.Google Scholar
Henderson, G. E. and Davis, A. M. et al., “Uncertain Benefit: Investigators' Views and Communications in Early Phase Gene Transfer Trials,” Molecular Therapy 10, no. 2 (2004): 225–31.CrossRefGoogle Scholar
See Lo, , supra note 16.Google Scholar
See Weaver, , 2009; Benabid, , 2009, supra note 6.Google Scholar
See Lo, , supra note 16.Google Scholar
Horng, S. H. and Miller, F. G., “Placebo-Controlled Procedural Trials for Neurological Conditions,” Neurotherapeutics 4, no. 3 (2007): 531–6.CrossRefGoogle Scholar
Macklin, R., “The Ethical Problems with Sham Surgery in Clinical Research,” New England Journal of Medicine 341, no. 13 (1999): 992–6.CrossRefGoogle Scholar
See Horng, , supra note 25.Google Scholar
Kim, S. Y. and Frank, S. et al., “Science and Ethics of Sham Surgery: A Survey of Parkinson Disease Clinical Researchers,” Archives of Neurology 62, no. 9 (2005): 13571360.CrossRefGoogle Scholar
Frank, S. A., Wilson, R. et al., “Ethics of Sham Surgery: Perspective of Patients,” Movement Disorders 23, no. 1 (2008): 6368.CrossRefGoogle Scholar
See Weaver, , 2009 and Benabid, , 2009, supra note 6.Google Scholar
Fleming, T. R., Prentice, R. L., Pepe, M. S., and Glidden, D., “Surrogate and Auxiliary Endpoints in Clinical Trials, with Potential Applications in Cancer and Aids Research.” Statistics in Medicine 13, (1994): 955–68.CrossRefGoogle Scholar
See Freed, , supra note 7.Google Scholar
Arkin, L. M. and Sondhi, D. et al., “Confronting the Issues of Therapeutic Misconception, Enrollment Decisions, and Personal Motives in Genetic Medicine-Based Clinical Research Studies for Fatal Disorders,” Human Gene Therapy 16, no. 9 (2005): 10281036.CrossRefGoogle Scholar
See Lo, , supra note 4.Google Scholar
Lindvall, O. and Kokaia, Z., “Prospects of Stem Cell Therapy for Replacing Dopamine Neurons in Parkinson's Disease,” Trends in Pharmacological Sciences 30, no. 5 (2009): 260267.CrossRefGoogle Scholar
Institute of Medicine, Responsible Research: A Systems Approach to Protecting Research Participants (Washington, D.C.: National Academies Press, 2003).Google Scholar
National Academy of Sciences, “Guidelines for Human Embryonic Stem Cell Research,” National Academy Press, available at <http://books.nap.edu/catalog.php?record_id=11278> (last visited April 5, 2010).+(last+visited+April+5,+2010).>Google Scholar
National Institutes of Health, “Notice of Actions under the Nih Guidelines for Rsearch Involving Recombinant DNA Molecules,” Federal Register 65 (2000): 60627–332.Google Scholar
Scharschmidt, T. and Lo, B., “Clinical Trial Design Issues Raised During Recombinant DNA Advisory Committee Review of Gene Transfer Protocols,” Human Gene Therapy 17, no. 4 (2006): 448454.CrossRefGoogle Scholar
National Cancer Institute, “The Central Institutional Review Board Initiative,” available at <http://www.ncicirb.org/> (last visited April 5, 2010).+(last+visited+April+5,+2010).>Google Scholar
Biomedical Research Alliance of New York, available at <http://www.brany.com/> (last visited April 5, 2010); Multicenter Academic Centers Research Organization, available at <http://www.med.upenn.edu/ohr/aboutmacro.html> (last visited April 5, 2010).+(last+visited+April+5,+2010);+Multicenter+Academic+Centers+Research+Organization,+available+at++(last+visited+April+5,+2010).>Google Scholar
Tully, S., “The Party's Over,” Fortune, June 26 2000, 156.Google Scholar
Steinbrook, R., “The Gelsinger Case,” in Emanuel, , supra note 18, at 110120.Google Scholar
See Lo, , supra note 4.Google Scholar
Berg, J. W., Lidz, C. W., and Appelbaum, P. S., Informed Consent: Legal Theory and Clinical Practice, 2nd ed. (New York: Oxford University Press, 2001).Google Scholar
See Lo, , supra note 4.Google Scholar
Woodsong, C. and Karim, Q. A., “A Model Designed to Enhance Informed Consent: Experiences from the Hiv Prevention Trials Network,” American Journal of Public Health 95, no. 3 (2005): 412–9.CrossRefGoogle Scholar
National Bioethics Advisory Commission, Ethical and Policy Issues in Research Involving Human Participants (Rockville, MD: National Bioethics Advisory Commission, 2001).Google Scholar
See Hyun, , 2007 and Lo, , 2008, supra note 4.Google Scholar
See Steinbrook, , supra note 43; Couzin, J. and Kaiser, J., “Gene Therapy: As Gelsinger Case Ends, Gene Therapy Suffers Another Blow,” Science 307, no. 5712 (2005): 1028; Fox, R. C. and Swazey, J. P., Spare Parts (New York: Oxford University Press, 1992).Google Scholar
Lo, B. and Field, M.J., Conflicts of Interest in Medical Research, Education, and Clinical Practice (Washington, D.C.: National Academies Press, 2009).Google Scholar
Wood, A. J., “Progress and Deficiencies in the Registration of Clinical Trials.” N. Engl. J. Med. 360, no. 8 (2009): 824–30.CrossRefGoogle Scholar