Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study
Kalladka, Dheeraj ; Sinden, John ; Pollock, Kenneth ; Haig, Caroline ; McLean, John ; Smith, Wilma ; McConnachie, Alex ; Santosh, Celestine ; Bath, Philip M. ; Dunn, Laurence ; Muir, Keith W.
Philip M. Bath
Keith W. Muir
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.
|Journal Article Type||Article|
|Publication Date||Aug 20, 2016|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Kalladka, D., Sinden, J., Pollock, K., Haig, C., McLean, J., Smith, W., …Muir, K. W. (2016). Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. Lancet, 388(10046), 787-796. https://doi.org/10.1016/S0140-6736%2816%2930513-X|
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