Novel Approaches to Neuroprotection Trials in Acute Ischemic Stroke

Tymianski, Michael

doi:10.1161/strokeaha.113.000731

Cited by 77 publications

(64 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, safe and effective neuroprotective drugs have been sought. Although the mechanism of neuroprotection is not entirely clear, the basic aim of this strategy is to interfere with pathological processes by blocking the ischemic cascade reaction and preventing the nerve cells from dying following ischemia (20).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

Xue

Zhang

Zhao

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

Xue

Zhang

Zhao

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The reasons for this failure have been extensively discussed 24, 25, 26. Clinically, patient selection may be among the most important factors that should be considered when designing trials in stroke.…”

Section: Discussionmentioning

confidence: 99%

The value of patient selection in demonstrating treatment effect in stroke recovery trials: lessons from the CHIMES study of MLC601 (NeuroAiD)

Venketasubramanian

Lee

Wong

et al. 2015

Journal of Evidence-Based Medicine

View full text Add to dashboard Cite

ObjectiveThe CHIMES Study compared MLC601 to placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. We aimed to verify if patient selection based on two prognostic factors (ie, stroke severity and time to treatment) improves detection of a treatment effect with MLC601.MethodsAnalyses were performed using data from the CHIMES Study, an international, randomized, placebo‐controlled, double‐blind trial comparing MLC601 to placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. Three subgroups, that is, onset to treatment time (OTT) ≥48 hours; baseline National Institute of Health Stroke Scale (NIHSS) ≥10; both OTT ≥48 hours and baseline NIHSS ≥10, were analyzed using modified Rankin Scale (mRS) ≤1 and a composite endpoint of mRS ≤1, Barthel Index ≥95, and NIHSS ≤1 at month 3.ResultsPlacebo response rates were lower (ie, worse natural outcome) among subgroups with prognostic factors. Conversely, MLC601 treatment effects were significantly higher in the subgroups with prognostic factors than for the entire cohort, being highest among patients with both OTT ≥48 hours and baseline NIHSS of 10 to 14: odds ratios of 2.18 (95% CI 1.02 to 4.65) for month 3 mRS ≤1 and 3.88 (95% CI 1.03 to 14.71) for the composite endpoint.Conclusions: Patients who have moderately severe strokes and longer OTT demonstrate better treatment effects with MLC601. These factors can guide patient selection in future trials.

show abstract

“…While many neuroprotective drugs have been developed, none of these drugs have been translated to the clinical setting (O'Collins et al, 2006;Tymianski, 2013). This failure could be explained by the lack of consideration for the risk factors for stroke, including aging, permanent occlusion and long-term follow up in pre-clinical studies (Turner et al, 2013).…”

Section: Neuroprotective Strategies For Ischemic Strokementioning

confidence: 99%

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

Belayev

Khoutorova

Hong

et al. 2015

OCL

View full text Add to dashboard Cite

-Despite tremendous efforts in ischemic stroke research and significant improvements in patient care within the last decade, therapy is still insufficient. There is a compelling, urgent need for safe and effective neuroprotective strategies to limit brain injury, facilitate brain repair, and improve functional outcome. Recently, we reported that docosahexaenoic acid (DHA; 22:6, n-3) complexed to human albumin (DHA-Alb) is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo) in young rats. This review highlights the potency of DHA-Alb therapy in permanent MCAo and aged rats and whether protection persists with chronic survival. We discovered that a novel therapy with DHA-Alb improved behavioral outcomes accompanied by attenuation of lesion volumes even when animals were allowed to survive three weeks after experimental stroke. This treatment might provide the basis for future therapeutics for patients suffering from ischemic stroke.Keywords: Omega-3 polyunsaturated fatty acids / neuroprotection / behavior / MRI / histopathology Résumé -Une nouvelle stratégie thérapeutique pour les AVC expérimentaux utilisant l'acide docosahexaénoïque complexé à l'albumine humaine. En dépit des avancées de la recherche sur l'AVC ischémique et des amé-liorations significatives des soins apportés aux patients durant la dernière décennie, la thérapie de prise en charge demeure encore insuffisante. Ainsi, il est urgent de développer des stratégies neuroprotectrices sûres et efficaces afin de limiter le développement des lésions cérébrales et de restaurer les altérations cellulaires et fonctionnelles. Récemment, nous avons mis en évidence que l'acide docosahexaénoïque (DHA ; 22:6, n-3) complexé à l'albumine humaine (DHAAlb) s'avère hautement neuroprotecteur chez le jeune rat après une occlusion cérébrale moyenne temporaire de l'artère (MCAo). Cette revue met en avant tout le potentiel d'une thérapie DHA-Alb chez des rats MCAo permanents et âgés, et soulève la question de la persistance de la neuroprotection en condition de survie prolongée. Cette nouvelle théra-pie de traitement avec du DHA-Alb améliore par ailleurs les performances comportementales et s'accompagne d'une régression volume des lésions cérébrales même après 3 semaines suivant l'AVC expérimental. Ce type de traitement pourrait ainsi constituer une nouvelle base de prise en charge des patients atteints d'un AVC ischémique.Mots clés : Oméga-3 / acides gras poly-insaturés / neuroprotection / comportement / IRM / histopathologie

show abstract

Novel Approaches to Neuroprotection Trials in Acute Ischemic Stroke

Cited by 77 publications

References 70 publications

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

The value of patient selection in demonstrating treatment effect in stroke recovery trials: lessons from the CHIMES study of MLC601 (NeuroAiD)

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

Contact Info

Product

Resources

About