1. Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study.
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Kalladka, Dheeraj, Sinden, John, Pollock, Kenneth, Haig, Caroline, McLean, John, Smith, Wilma, McConnachie, Alex, Santosh, Celestine, Bath, Philip M., Dunn, Laurence, and Muir, Keith W.
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NEURAL stem cells , *STROKE treatment , *CORONARY disease , *MEDICATION safety , *SENSORIMOTOR cortex , *BRAIN imaging , *MAGNETIC resonance imaging , *PATIENTS , *PHYSIOLOGY , *THERAPEUTICS , *RADIOGRAPHY , *BASAL ganglia , *BRAIN , *CEREBRAL ischemia , *CHRONIC diseases , *CLINICAL trials , *COMPARATIVE studies , *COMPUTED tomography , *INFARCTION , *INJECTIONS , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *STEM cells , *STEREOTAXIC techniques , *TIME , *PILOT projects , *EVALUATION research , *TREATMENT effectiveness , *DISEASE complications - 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.Funding: ReNeuron Limited. [ABSTRACT FROM AUTHOR]- Published
- 2016
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