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.
Funding ReNeuron, Innovate UK (application no 32074-222145).
Trial registration number EudraCT Number: 2012-003482-18
- stem cells
- human neural stem cells
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Presented at International Stroke Conference 2018
Contributors The trial protocol was designed by JH, PS, KP and JS with input from AM, LD and other clinical investigators. Data were acquired by KWM, DB, MW, NS, AD, NW, PT and LD. PB chaired the data monitoring committee. KWM undertook analyses and drafted the manuscript. The manuscript was critically reviewed by DB, MW, NS, AD, NW, PT, AM, LD, PB, KP and JS.
Funding This study was funded by ReNeuron Ltd., Innovate UK (application no 32074-222145).
Competing interests JH, PS, KP and JS are employees of ReNeuron. KWM has participated in advisory boards for ReNeuron and is a member of the trial steering committee for the PISCES-3 trial.
Patient consent for publication Not required.
Ethics approval The study was approved by the UK National Research Ethics Service and Gene Therapy Advisory Committee (references 13/LO1174, GTAC161, 12/LO/1963).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information. All relevant data are included in online suppplementary information.
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