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Open Access 01-03-2019 | Review

Renewed assessment of the risk of emergent advanced cell therapies to transmit neuroproteinopathies

Authors: Paul A. De Sousa, Diane Ritchie, Alison Green, Siddharthan Chandran, Richard Knight, Mark W. Head

Published in: Acta Neuropathologica | Issue 3/2019

Abstract

The inadvertent transmission of long incubating, untreatable and fatal neurodegenerative prionopathies, notably iatrogenic Creutzfeldt–Jakob disease, following transplantation of cadaver-derived corneas, pituitary growth, hormones and dura mater, constitutes a historical precedent which has underpinned the application of precautionary principles to modern day advanced cell therapies. To date these have been reflected by geographic or medical history risk-based deferral of tissue donors. Emergent understanding of other prion-like proteinopathies, their potential independence from prions as a transmissible agent and the variable capability of scalably manufacturable stem cells and derivatives to take up and clear or to propagate prions, substantiate further commitment to qualifying neurodegenerative proteinopathy transmission risks. This is especially so for those involving direct or facilitated access to a recipient’s brain or connected visual or nervous system such as for the treatment of stroke, retinal and adult onset neurodegenerative diseases, treatments for which have already commenced. In this review, we assess the prospective global dissemination of advanced cell therapies founded on transplantation or exposure to allogeneic human cells, recap lessons learned from the historical precedents of CJD transmission and review recent advances and current limits in understanding of prion and other neurodegenerative disease prion-like susceptibility and transmission. From these we propose grounds for a reassessment of the risks of emergent advanced cell therapies to transmit neuroproteinopathies and suggestions to ACT developers and regulators for risk mitigation and extension of criteria for deferrals.

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Title: Renewed assessment of the risk of emergent advanced cell therapies to transmit neuroproteinopathies
Authors: Paul A. De Sousa
Diane Ritchie
Alison Green
Siddharthan Chandran
Richard Knight
Mark W. Head
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 3/2019
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-018-1941-9

At a glance: The STEP trials

Springer Medicine

Renewed assessment of the risk of emergent advanced cell therapies to transmit neuroproteinopathies

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study

Amyloid-β pathology enhances pathological fibrillary tau seeding induced by Alzheimer PHF in vivo

ACTN2 mutations cause “Multiple structured Core Disease” (MsCD)