title: Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ReNeuron Limited.
authors: Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
authors: Dheeraj
authors: D
authors: Kalladka
authors: ReNeuron Ltd, Surrey Research Park, Guildford, Surrey, UK.
authors: John
authors: J
authors: Sinden
authors: ReNeuron Ltd, Surrey Research Park, Guildford, Surrey, UK.
authors: Kenneth
authors: K
authors: Pollock
authors: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors: Caroline
authors: C
authors: Haig
authors: Department of Neuroradiology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
authors: John
authors: J
authors: McLean
authors: Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
authors: Wilma
authors: W
authors: Smith
authors: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors: Alex
authors: A
authors: McConnachie
authors: Department of Neuroradiology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
authors: Celestine
authors: C
authors: Santosh
authors: Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK.
authors: Philip M
authors: PM
authors: Bath
authors: Neurosurgery, Institute of Neurological Sciences, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
authors: Laurence
authors: L
authors: Dunn
authors: Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK. Electronic address: keith.muir@glasgow.ac.uk.
authors: Keith W
authors: KW
authors: Muir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications*; D002544:Cerebral Infarction / Q000209:etiology / Q000628:therapy*; D002908:Chronic Disease; D056324:Diffusion Tensor Imaging; D005240:Feasibility Studies; D006801:Humans; D007267:Injections; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells; D010865:Pilot Projects; D011699:Putamen; D013238:Stereotaxic Techniques; D020521:Stroke / Q000628:therapy; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D006113:United Kingdom