Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

Muir, K. W. et al. (2020) Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2). Journal of Neurology, Neurosurgery and Psychiatry, 91(4), pp. 396-401. (doi: 10.1136/jnnp-2019-322515) (PMID:32041820)

Abstract

BACKGROUND: Human neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute-chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study. METHODS: We undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2-13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation. FINDINGS: Twenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures. INTERPRETATION: Administration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials.

• Item Type: Articles
• Additional Information: Funding: ReNeuron Ltd., Innovate UK (application no 32074-222145). AM was partially supported by the National Institute for Health Research (NIHR) Sheffield Biomedical Research Centre (BRC) and NIHR Sheffield Clinical Research Facility.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dunn, Mr Laurence and Muir, Professor Keith
• Authors: Muir, K. W., Bulters, D., Willmot, M., Sprigg, N., Dixit, A., Ward, N., Tyrrell, P., Majid, A., Dunn, L., Bath, P. M., Howell, J., Stroemer, P., Pollock, K., and Sinden, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Neurology, Neurosurgery and Psychiatry
• Publisher: BMJ Publishing Group
• ISSN: 0022-3050
• ISSN (Online): 1468-330X
• Published Online: 10 February 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Journal of Neurology, Neurosurgery and Psychiatry 91(4):396-401
• Publisher Policy: Reproduced under a Creative Commons licence