scholarly journals Technical Approach to Local Therapy in Ischemic Stroke

2020 ◽  
Vol 10 (1) ◽  
pp. 92-97
Author(s):  
Fernando José Rascón Ramirez ◽  
Juan Antonio Barcia ◽  
Cristina Nombela ◽  
Leyre Sanchez Sanchez de Rojas
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Surgical Technique ◽  
Therapeutic Target ◽  
Short Communication ◽  
Neurological Diseases ◽  
Local Therapy ◽  
Technical Approach

Local therapy is an increasingly achievable alternative for neurological diseases such as stroke. For its use to be a reality, it is still necessary to develop techniques that facilitate its administration and maximize its effect. In this short communication, we present a technique of intracerebral therapy administration. This procedure requires the use a navigation-guided stereotactic surgical technique to inject the treatment into the therapeutic target, even in areas that are difficult to access or extremely large. Such a method is not only fast and feasible, but it can be a standardized technique for multicentre clinical trials.

scholarly journals Cell Therapies under Clinical Trials and Polarized Cell Therapies in Pre-Clinical Studies to Treat Ischemic Stroke and Neurological Diseases: A Literature Review

2020 ◽  
Vol 21 (17) ◽  
pp. 6194 ◽  
Author(s):  
Masahiro Hatakeyama ◽  
Itaru Ninomiya ◽  
Yutaka Otsu ◽  
Kaoru Omae ◽  
Yasuko Kimura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Clinical Studies ◽  
Mononuclear Cells ◽  
Neurological Diseases ◽  
Functional Independence ◽  
Therapeutic Effects ◽  
Cell Therapies ◽  
Neuronal Stem Cells

Stroke remains a major cause of serious disability because the brain has a limited capacity to regenerate. In the last two decades, therapies for stroke have dramatically changed. However, half of the patients cannot achieve functional independence after treatment. Presently, cell-based therapies are being investigated to improve functional outcomes. This review aims to describe conventional cell therapies under clinical trial and outline the novel concept of polarized cell therapies based on protective cell phenotypes, which are currently in pre-clinical studies, to facilitate functional recovery after post-reperfusion treatment in patients with ischemic stroke. In particular, non-neuronal stem cells, such as bone marrow-derived mesenchymal stem/stromal cells and mononuclear cells, confer no risk of tumorigenesis and are safe because they do not induce rejection and allergy; they also pose no ethical issues. Therefore, recent studies have focused on them as a cell source for cell therapies. Some clinical trials have shown beneficial therapeutic effects of bone marrow-derived cells in this regard, whereas others have shown no such effects. Therefore, more clinical trials must be performed to reach a conclusion. Polarized microglia or peripheral blood mononuclear cells might provide promising therapeutic strategies after stroke because they have pleiotropic effects. In traumatic injuries and neurodegenerative diseases, astrocytes, neutrophils, and T cells were polarized to the protective phenotype in pre-clinical studies. As such, they might be useful therapeutic targets. Polarized cell therapies are gaining attention in the treatment of stroke and neurological diseases.

scholarly journals Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Bartosz Karaszewski ◽  
Adam Wyszomirski ◽  
Bartosz Jabłoński ◽  
David J. Werring ◽  
Dominika Tomaka
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Randomized Clinical Trials ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Vessel Occlusion ◽  
Excellent Outcome ◽  
Symptomatic Intracerebral Hemorrhage

AbstractIntravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0–1 and 0–2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29–1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31–2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76–28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%–1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.

Current Perspectives Regarding Stem Cell-based Therapy for Ischemic Stroke

2018 ◽  
Vol 24 (28) ◽  
pp. 3332-3340 ◽  
Author(s):  
Kyeong-Ah Kwak ◽  
Ho-Beom Kwon ◽  
Joo Won Lee ◽  
Young-Seok Park
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Time Window ◽  
Experimental Studies ◽  
Cell Type ◽  
Stroke Treatment ◽  
Cell Based Therapy ◽  
Regenerative Approach ◽  
Therapeutic Time Window

Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection, neurogenesis, angiogenesis, immunomodulation, and anti-inflammatory effects. Despite the promising features shown in experimental studies, results from clinical trials are inconclusive from the perspective of efficacy. The present review presents a synopsis of stem cell research on ischemic stroke treatment according to cell type. Clinical trials to the present are briefly summarized. Finally, the hurdles and issues to be solved are discussed for clinical application.

Abstract TP409: Reporting of Key Demographic Characteristics in Neurological Trials Registered on ClinicalTrials.gov

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kush Fansiwala ◽  
Lauren Southwick ◽  
Emily Goldmann ◽  
Nina S Parikh ◽  
Joy Madubuonwu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Race And Ethnicity ◽  
Neurological Diseases ◽  
Demographic Characteristics ◽  
Mandatory Reporting ◽  
Trial Participation ◽  
Limited Participation ◽  
Chi Square ◽  
Before And After ◽  
Race Ethnicity

Introduction: To increase the transparency of clinical trial information, U.S. Congress passed the Food and Drug Administration (FDA) Amendments Act of 2007, which expanded prior legislation to mandate inclusion of specific trial characteristics, such as funding source and gender demographics, in a new basic results section on ClinicalTrials.gov. Few studies have examined the extent to which key demographic characteristics such as sex and race/ethnicity are reported for neurological trials on ClinicalTrials.gov. Methods: As part of the National Initiative for Minority Involvement in Neurological Clinical Trials (NIMICT), we systematically identified neurological clinical trials on ClinicalTrials.gov (for stroke, epilepsy, Alzheimer’s Disease [AD]) and examined the proportion that reported sex, race, and ethnicity (Hispanic/Latino or not) of study participants. We used the website’s advanced search feature to evaluate demographic information reported from trials conducted between 1999 and 2015. We first calculated frequencies of trials reporting these characteristics, then assessed differences in reporting of each characteristic (yes/no) by condition (stroke, epilepsy, AD) and between trials conducted before and after the basic results section update (pre- and post-2008) using chi-square tests. Results: Our sample comprised 251,847 subjects across 393 trials (147 stroke, 127 epilepsy, 115 AD). Overall, sex was reported for nearly all trials (99.0%), while reporting of race and ethnicity was low (ethnicity: 14.0%, race: 19.8%). Reporting of these characteristics did not differ significantly across the three conditions or between periods preceding and following the FDA act. Conclusion: While ClinicalTrials.gov mandates reporting of sex, it does not require reporting of race/ethnicity, and few trials report these characteristics. This lack of information prevents understanding of neurological trial participation and how interventions might impact patients differently by race/ethnicity. Mandatory reporting of race/ethnicity would enhance transparency and increase awareness of the limited participation of racial/ethnic minorities-who suffer disproportionately from neurological diseases-in neurological trials.

scholarly journals Progenitor Cell Therapy for the Treatment of Central Nervous System Injury: A Review of the State of Current Clinical Trials

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Peter A. Walker ◽  
Matthew T. Harting ◽  
Shinil K. Shah ◽  
Mary-Clare Day ◽  
Ramy El Khoury ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Progenitor Cell ◽  
Neurological Injury ◽  
Cell Therapies ◽  
Potential Efficacy ◽  
Cord Injury

Recent preclinical work investigating the role of progenitor cell therapies for central nervous system (CNS) injuries has shown potential neuroprotection in the setting of traumatic brain injury (TBI), spinal cord injury (SCI), and ischemic stroke. Mechanisms currently under investigation include engraftment and transdifferentiation, modulation of the locoregional inflammatory milieu, and modulation of the systemic immunologic/inflammatory response. While the exact mechanism of action remains controversial, the growing amount of preclinical data demonstrating the potential benefit associated with progenitor cell therapy for neurological injury warrants the development of well-controlled clinical trials to investigate therapeutic safety and efficacy. In this paper, we review the currently active or recently completed clinical trials investigating the safety and potential efficacy of bone marrow-derived progenitor cell therapies for the treatment of TBI, SCI, and ischemic stroke. Our review of the literature shows that while the preliminary clinical trials reviewed in this paper offer novel data supporting the potential efficacy of stem/progenitor cell therapies for CNS injury, a great deal of additional work is needed to ensure the safety, efficacy, and mechanisms of progenitor cell therapy prior to widespread clinical trials.

Mitochondria as a therapeutic target for ischemic stroke

2020 ◽  
Vol 146 ◽  
pp. 45-58 ◽  
Author(s):  
Zhi He ◽  
Niya Ning ◽  
Qiongxiu Zhou ◽  
Seyed Esmaeil Khoshnam ◽  
Maryam Farzaneh
Keyword(s):  
Ischemic Stroke ◽  
Therapeutic Target

Inflammation as a Therapeutic Target in Acute Ischemic Stroke Treatment

2009 ◽  
Vol 9 (14) ◽  
pp. 1240-1260 ◽  
Author(s):  
Antonino Tuttolomondo ◽  
Riccardo Di Sciacca ◽  
Domenico Di Raimondo ◽  
Chiara Renda ◽  
Antonio Pinto ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Therapeutic Target ◽  
Stroke Treatment

Progress in research on the role of Omi/HtrA2 in neurological diseases

2019 ◽  
Vol 30 (3) ◽  
pp. 279-287 ◽  
Author(s):  
Xiao Juan Su ◽  
Lingyi Huang ◽  
Yi Qu ◽  
Dezhi Mu
Keyword(s):  
Cell Death ◽  
Signaling Pathways ◽  
Serine Protease ◽  
Brain Damage ◽  
Therapeutic Target ◽  
Neurological Diseases ◽  
Mitochondrial Matrix ◽  
Ischemic Brain ◽  
External Signals

Abstract Omi/HtrA2 is a serine protease present in the mitochondrial space. When stimulated by external signals, HtrA2 is released into the mitochondrial matrix where it regulates cell death through its interaction with apoptotic and autophagic signaling pathways. Omi/HtrA2 is closely related to the pathogenesis of neurological diseases, such as neurodegeneration and hypoxic ischemic brain damage. Here, we summarize the biological characteristics of Omi/HtrA2 and its role in neurological diseases, which will provide new hints in developing Omi/HtrA2 as a therapeutic target for neurological diseases.

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