Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study.
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2018-07
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Stroke is a major cause of death and long-term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase I open-label trial to assess the safety and feasibility of a single IV infusion of non-human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3-9 days post-stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well-tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post-treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non-HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo-controlled phase 2 study. Stem Cells Translational Medicine 2018;7:521-529.
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Laskowitz, Daniel T, Ellen R Bennett, Rebecca J Durham, John J Volpi, Jonathan R Wiese, Michael Frankel, Elizabeth Shpall, Jeffry M Wilson, et al. (2018). Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study. Stem cells translational medicine, 7(7). pp. 521–529. 10.1002/sctm.18-0008 Retrieved from https://hdl.handle.net/10161/22425.
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Daniel Todd Laskowitz
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical setting of stroke, intracranial hemorrhage, and closed head injury.
In conjunction with the Multidisciplinary Neuroprotection Laboratories, we also focus on clinically relevant small animal models of acute CNS injury. For example, we have recently characterized murine models of closed head injury, subarachnoid hemorrhage, intracranial hemorrhage and perinatal hypoxia-ischemia, in addition to the standard rodent models of focal stroke and transient forebrain ischemia. Recently we have adapted several of these models from the rat to the mouse to take advantage of murine transgenic technology. The objective of these studies are two-fold: to gain better insight into the cellular responses and pathophysiology of acute brain injury, and to test novel therapeutic strategies for clinical translation. In both cell culture systems and animal models, our primary focus is on examining the role of oxidative stress and inflammatory mechanism in mediating brain injury following acute brain insult, and examining the neuroprotective effects of endogenous apolipoprotein E in the injured mammalian central nervous system.
Our laboratory is committed to translational research, and has several active clinical research protocols, which are designed to bring the research performed in the Multidisciplinary Research Laboratories to the clinical arena. These protocols are centered around patients following stroke and acute brain injury, and are primarily based out of the Emergency Room and Neurocritical Care Unit. For example, we are currently examining the role of inflammatory mediators for use as a point-of-care diagnostic marker following stroke, intracranial hemorrhage, and closed head injury. We have recently translated a novel apoE mimetic from the preclinical setting to a multi center Phase 2 trial evaluating efficacy in intracranial hemorrhage. We are also examining the functional role of different polymorphisms of of inflammatory cytokines in the setting of acute brain injury and neurological dysfunction following cardiopulmonary bypass.
Ellen Ruth Bennett
Jesse David Troy
I am the Associate Director of Graduate Studies for the Master of Biostatistics program. I am also an instructor in the Clinical Research Training Program. I work on research studies in cancer therapeutics and palliative care at the Duke Cancer Institute.
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