London, United Kingdom 2013 Poster Session Red Cerebrovasc Dis 2013; 35 (suppl 3)1-854 551 495 Translational stroke research Pilot Investigation of Stem Cells in Stroke PISCES A Phase I Trial of CTX0E03 Human Neural Stem Cells D. Kalladka1, J. Sinden2, K. Pollock3, J. McLean4, L. Dunn5, C. Santosh6, K.W. Muir7 Stroke Research Group, Southern General Hospital, Glasgow, UK Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UNITED KING-DOM1, ReNeuron Ltd., Surrey, UNITED KINGDOM2, ReNeuron Ltd., Surrey, UNITED KING-DOM3, Dept. of Neuroradiology, Institute of Neurological Sciences, NHS Greater Glasgow & Clyde, Glasgow, UNITED KINGDOM4, Dept. of Neurosurgery, Institute of Neurological Sciences, NHS Greater Glasgow & Clyde, Glasgow, UNITED KINGDOM5, Dept. of Neuroradiology, Insti-tute of Neurological Sciences, NHS Greater Glasgow & Clyde, Glasgow, UNITED KINGDOM6, Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UNITED KINGDOM7 Background: CTX0E03 is a conditionally immortalized human neural stem cell line, developed as a GMP manufactured, allogeneic, Advanced Therapy Medicinal Product. After direct cerebral im-plantation 4 weeks after rat MCAo stroke, CTX0E03 exhibited dose-dependent improved functional outcome, along with increased host striatal angiogenesis and neurogenesis. Aim: To investigate the safety profile of intra-cerebral implantation of CTX0E03. Methods: This was an open label, single site, ascending dose trial in 12 male patients with stable disability (NIHSS≥6, mRS>1) after isch-aemic MCA stroke 6 - 60 months previously. Four groups of 3 each receive 2, 5, 10 & 20 million cells respectively, implanted in ipsilateral putamen by stereotaxic injection. Clinical (NIHSS, mRS, BI, Ashworth, EuroQoL) & radiological data are collected over 2 years. The primary endpoint is safety, including adverse events, neurological change or mortality, with secondary functional end-points. Results: By 10thJan2013, nine patients had received CTX0E03 2, 5, 10m cells; each n=3. Follow-up was 3-24 months. Mean age was 69 years; median pre-implantation NIHSS score 8, and mean time from stroke 26 months. Three had sub-cortical-only infarcts and 5 had right hemisphere stroke. No cell-related or immunological adverse events were observed. Post-implantation, 1 patient had an asymptomatic subdural bleed and 1 had an asymptomatic contralateral occipital infarct. NI-HSS score improved by median 1 point at 1 mth post-treatment (n=9) and 3 points at 1 year (n=5). Median BI improved by 1 point at 3 mths (n=8) and 4 points at 1 year (n=5). Median mRS improved by 1 grade at 1 year (n=4/5). Summated Ashworth scores for affected limbs improved by mean 8 (2- 14) at 3 mths (n=8) and 10 (6-17) at 1 year (n=5). Conclusion: No cell related adverse events have been observed to date in doses up to 10 million CTX0E03 cells. Observed improvements on neuro-logical measures justify further investigation in a Phase II study. 496Translational stroke research Role of Oxidative Stress in Mediating Vascular Brain Damage: Hyperacute Plasma F2-Iso-prostane Predicts Infarct Growth in Ischemic Stroke S. Lorenzano1, N.S. Rost2, H. Li3, F.O. Lima4, M.B. Maas5, A.J. Dipietro6, K. Arai7, D. Toni8, O. Wu9, G.J. Harris10, E.H. Lo11, J.B. Blumberg12, S.K. Feske13, K.L. Furie14 Massachusetts General Hospital/Harvard Medical School and Sapienza University of Rome, Boston, USA1, Massachusetts General Hospital and Harvard Medical School, Boston, USA2, Mas-sachusetts General Hospital and Harvard Medical School, Boston, USA3, Massachusetts General Hospital and Harvard Medical School, Boston, USA4, Massachusetts General Hospital and Harvard Medical School, Boston, USA5, Massachusetts General Hospital and Harvard Medical School, Bos-ton, USA6, Massachusetts General Hospital and Harvard Medical School, Boston, USA7, Sapienza University of Rome, Rome, ITALY8, Massachusetts General Hospital and Harvard Medical School, Boston, USA9,Massachusetts General Hospital and Harvard Medical School, Boston, USA10, Mas-sachusetts General Hospital and Harvard Medical School, Boston, USA11, Tufts University, Boston, USA12, Massachusetts General Hospital and Harvard Medical School, Boston, USA13, Massachu-setts General Hospital and Harvard Medical School, Boston, USA14, , , 15 Background:Oxidative stress occurs as part of the earliest response to cerebral ischemia and is likely to play an important role in the pathogenesis of ischemic brain injury. We sought to evaluate wheth-er hyperacute plasma levels of F2-isoprostane (F2-isoP) predict infarct growth (IG). Methods:We prospectively measured plasma F2-isoP, urinary 8-oxo-7,8-dihydro-2’-deoxyguoanosine, plasma Oxygen Radical Absorbance Capacity assay, high sensitivity-C reactive protein, and matrix metallo-proteinase- 2 and -9 in acute ischemic stroke(AIS) patients presenting within 9 h of symptom onset. Baseline DWI volume(DWIV) and final infarct volume(FIV) (DWI or CT at 24-96h) were analyzed using semi-automated volumetric method. IG volume(IGV) was defined as the difference between FIV and baseline DWIV. Results:Of 489 AIS subjects, 220 mean (SD) age 69.4 (14.7) y, 40.9% females, 55.7% treated with IV t-PA had both baseline DWI and follow-up imaging.Of these, 170 had IG, and they were more likely to be male(p=0.03), under statins(p=0.01), to have prior transient ischemic attack(p=0.046), diabetes mellitus(p=0.03), higher NIHSS score(p=0.01) and blood glu-cose levels(p=0.03) at admission, a larger DWIV(p=0.01), and higher median (IQR) baseline levels of F2-isoP 56.2(36.4-75.3) vs. 42.0(27.0-61.8) pg/mL, p=0.009.Baseline F2-isoP significantly cor-related with IGV(Spearman’s rho=0.20,p=0.005) and FIV(Spearman’s rho=0.19,p=0.009). In a mul-tivariate binary logistic regression model, baseline F2-isoP emerged as an independent predictor of IG occurrence(OR 2.57, 95%CI 1.37-4.83; p=0.007). In a multivariate linear regression model, F2- isoP was independently associated with IGV (B 0.38, 95%CI 0.04-0.72; p=0.03). Conclusions:Ele-vated hyperacute plasma F2-isoP concentrations independently predict IG and IGV in AIS patients. If validated in future studies, measuring plasma F2-isoP might be helpful in the acute setting to strat-ify patients for progression and relative severity of ischemic injury.
Karger_ESC London_2013
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