Resumo da palestra NurAiD II na recuperação do AVC: Fundamentos científicos e experiência clínica, pelo Dr. Carlos de la Cruz Cosme no Curso de Atualização em Doença Vascular Cerebral, Faculdade de Medicina da Universidade do Porto, 21 de junho de 2017, publicado no INTERNATIONAL JOURNAL OF CLINICAL NEUROSCIENCES AND MENTAL HEALTH.
Hossein Pakdaman (a), Ali Amini Harandi (a), Hamidreza Hatamian (c), Mojgan Tabatabae (b), Hosein Delavar Kasmaei (a), Amirhossein Ghassemi (d), Koroush Gharagozli a Farzad Ashrafi a Pardis Emami Naeini (e), Mehrnaz Tavakolian (a), Darush Shahin (a). (a) - Department of Neurology, Shahid Beheshti University of Medical Sciences, and (b) - Social Security, Tehran , (c) - Department of Neurology, Rasht University of Medical Sciences, Rasht (d) - Social Security, Kerman , and e School of Medicine, Isfahan University of Medical Sciences, Isfahan , Iran. Dement Geriatr Cogn Disord Extra 2015;5:96–106 Abstract Background: MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer’s disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. Methods: In a multicenter, nonblinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. Results: There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). Conclusion: MLC601 showed a promising safety profile and also efficacy compared to 3 FDA-approved ChEIs.
HYA Chan and LW Stanton. The Pharmacogenomics Journal (2016), 1–11 NeuroAiD, a traditional Chinese medicine widely used to treat stroke patients in China, was recently demonstrated in rodent models and in clinical trials to possess neuroregenerative and neuroprotective properties. In order to understand the mechanisms employed by NeuroAiD to bring about its neuroproliferative and neuroprotective effects, we investigated the impact of MLC901, a reformulated version of MLC601, on human neural progenitors undergoing neural differentiation at the molecular level by performing three independent microarray experiments. Functional annotations of the genes regulated by MLC901 that were associated with neurogenesis were found to be enriched. We also identified potential targets (FGF19, GALR2, MMP10, FGF3 and TDO2) of MLC901 that could promote neurogenesis and neuroprotection in the human brain. This work highlighted some interesting targets and offered some insights into the possible mechanism of action of MLC901. The discovery could also provide a platform to the development of future therapeutic targets.
Carine Gandin, Catherine Widmann, Michel Lazdunski, Catherine Heurteaux. Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS – Université de Nice Sophia Antipolis, Valbonne , France. Cerebrovasc Dis 2016;42:139–154 Background: There is increasing evidence that angiogenesis,through new blood vessel formation, results in improved collateral circulation and may impact the long-term recovery of patients. In this study, we first investigated the preventive action of a 5-week pretreatment of MLC901, an herbal extract preparation derived from Chinese medicine, against the deleterious effects of ischemic stroke and its effects on angiogenesis in a model of focal ischemia in mice. Methods: The stroke model was induced by 60 min of middle cerebral artery occlusion followed by reperfusion. MLC901 was administered in the drinking water of animals (6 g/l) for 5 weeks before ischemia and then during reperfusion. Results: MLC901 treatment increased the survival rate, reduced the cerebral infarct area and attenuated the blood brain barrier leakage as well as the neurologic dysfunction following ischemia and reperfusion. We provide evidence that MLC901 enhances endothelial cell proliferation and angiogenesis by increasing the number of neocortical vessels in the infarcted area. MLC901 regulates the expression of hypoxic inducible factor 1α and its downstream targets such as vascular endothelial growth factor and angiopoietins 1 and 2. This work also shows that erythropoietin is an important player in the enhancement of angiogenesis by MLC901. Conclusions: These results demonstrate therapeutic properties of MLC901, in addition to those previously described, in stimulating revascularization, neuroprotection and repair of the neurovascular unit after ischemic stroke.
Narayanaswamy Venketasubramanian, Chun Fan Lee, K. S. Lawrence Wong and Christopher L. H. Chen. Journal of Evidence-Based Medicine. Received 5 May 2015; accepted for publication 23 July 2015. doi: 10.1111/jebm.12170 Abstract Objective: The 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. Methods: Analyses 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 NIHSS10, were analyzed usingmodified Rankin Scale (mRS) 1 and a composite endpoint of mRS 1, Barthel Index 95, and NIHSS 1 at month 3. Results: Placebo 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.