Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study

Kalladka, D. et al. (2016) Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. Lancet, 388(10046), pp. 787-796. (doi:10.1016/S0140-6736(16)30513-X) (PMID:27497862)

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Abstract

Background: CTX0E03 is an immortalised human neural stem-cell line from which a drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients. Methods: We did an open-label, single-site, dose-escalation study. Men aged 60 years or older with stable disability (National Institutes of Health Stroke Scale [NIHSS] score ≥6 and modified Rankin Scale score 2–4) 6–60 months after ischaemic stroke were implanted with single doses of 2 million, 5 million, 10 million, or 20 million cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging data were collected over 2 years. The primary endpoint was safety (adverse events and neurological change). This trial is registered with ClinicalTrials.gov, number NCT01151124. Findings: 13 men were recruited between September, 2010, and January, 2013, of whom 11 (mean age 69 years, range 60–82) received CTX-DP. Median NIHSS score before implantation was 7 (IQR 6–8) and the mean time from stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven had right-hemisphere infarcts. No immunological or cell-related adverse events were seen. Other adverse events were related to the procedure or comorbidities. Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients. At 2 years, improvement in NIHSS score ranged from 0 to 5 (median 2) points. Interpretation: Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function. Our observations support further investigation of CTX-DP in stroke patients.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McConnachie, Professor Alex and Muir, Professor Keith and Smith, Mrs Wilma and Mclean, Dr John and Kalladka, Dr Dheeraj and Dunn, Mr Laurence and Haig, Dr Caroline and Santosh, Dr Celestine
Authors: Kalladka, D., Sinden, J., Pollock, K., Haig, C., McLean, J., Smith, W., McConnachie, A., Santosh, C., Bath, P. M., Dunn, L., and Muir, K. W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Lancet
Publisher:Elsevier
ISSN:0140-6736
ISSN (Online):1474-547X
Published Online:03 August 2016
Copyright Holders:Copyright © 2016 Elsevier
First Published:First published in Lancet 388(10046):787-796
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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