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)

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 Smith, Mrs Wilma and Mclean, Dr John and Kalladka, Dr Dheeraj and Dunn, Mr Laurence and Haig, Dr Caroline and Muir, Professor Keith 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 > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; 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