In vivo imaging of the integration and function of nigral grafts in clinical trials.

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  • Author(s): Politis M;Politis M; Piccini P
  • Source:
    Progress in brain research [Prog Brain Res] 2012; Vol. 200, pp. 199-220.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0376441 Publication Model: Print Cited Medium: Internet ISSN: 1875-7855 (Electronic) Linking ISSN: 00796123 NLM ISO Abbreviation: Prog Brain Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
      Clinical Trials as Topic*/instrumentation ; Clinical Trials as Topic*/methods ; Neuroimaging*; Brain Tissue Transplantation/*methods ; Parkinson Disease/*diagnosis ; Substantia Nigra/*physiology; Humans ; Parkinson Disease/surgery ; Substantia Nigra/transplantation
    • Abstract:
      In vivo functional imaging has provided objective evidence for the integration and function of nigral grafts in the brains of patients with Parkinson's disease. Clinical trials with the use of positron emission tomography have shown that transplants of human dopamine-rich fetal ventral mesencephalic tissue can survive, grow, and release dopamine providing motor symptom relief, and also that they can restore brain activation related to movement. Positron emission tomography has aided in the elucidation of the pathophysiology of serious adverse effects, so-called graft-induced dyskinesias. With the use of newly established radioligands, positron emission tomography and single-photon emission computed tomography could help to improve Parkinson's patient selection in future clinical trials by selecting those with better predicted outcomes. Moreover, positron emission tomography could help monitoring postoperational inflammatory processes around the grafted tissue and the effect of immunosuppression. Recent evidence from positron emission tomography has provided insight of how ongoing extrastriatal serotonergic denervation may have relevance to nonmotor symptoms in transplanted Parkinson's disease patients indicating new cell therapy targets for a more complete relief of symptoms. Functional and structural magnetic resonance imaging techniques could help to better assess the integration of nigral graft with the host brain by assessing the restoration of brain activation during movement and of functional and structural connectivity. This knowledge should lead to the development of new, optimized in vivo imaging protocols that could help to better schedule, monitor, and modify the clinical outcomes of future human trials assessing the efficacy of fetal or stem cell therapy in Parkinson's disease.
      (Copyright © 2012 Elsevier B.V. All rights reserved.)
    • Grant Information:
      G1100810 United Kingdom MRC_ Medical Research Council
    • Publication Date:
      Date Created: 20121201 Date Completed: 20131115 Latest Revision: 20220129
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/B978-0-444-59575-1.00009-0
    • Accession Number:
      23195420