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Outcome of cell suspension allografts in a patient with Huntington's disease.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Maxan, Alexander 
Saint-Pierre, Martine 
Smith, Emma 
Ho, Aileen 

Abstract

For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area. Our results indicate that grafts can survive more than a decade post-transplantation, but show compromised survival with inflammation and mutant protein being observed within the transplant site. Ann Neurol 2018;84:950-956.

Description

Keywords

Acetylcholinesterase, Adult, Allografts, Antigens, CD, Brain, Brain Tissue Transplantation, Calbindin 2, Humans, Huntingtin Protein, Huntington Disease, Interneurons, Male, Microglia, Nerve Tissue Proteins, Parvalbumins

Journal Title

Ann Neurol

Conference Name

Journal ISSN

0364-5134
1531-8249

Volume Title

84

Publisher

Wiley
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MC_PC_12009)
The trial was supported by a grant from the MRC and the follow up by NIHR funding of a Biomedical Research Centre in Cambridge to the Addenbrooke’s Hospital and University of Cambridge. AM is supported by the Fonds de Recherche du Québec en santé (FRQS) and the O’Brien Foundation. FC is a recipient of a Researcher Chair from FRQS providing salary support and operating funds, and receives funding from the Canadian Institutes of Health Research (CIHR) to conduct her HD-related research. RAB and SLM are supported by a grant from the MRC. RAB is a PI at the Wellcome Trust-MRC funded Cambridge Stem Cell Institute and an NIHR Senior Investigator.