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MC-1(pyridoxal 5'-phosphate):novel therapeutic applications to reduce ischaemic injury

机译:MC-1(吡rid醛5'-磷酸酯):减少缺血性损伤的新型治疗应用

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Despite the overall efficacy of mechanical reperfusion therapies,such as percutaneous coronary intervention and coronary artery bypass graft surgery,in reducing the morbidity and mortality that is associated with acute ischaemic syndromes,many of the treated patients develop ischaemia-reperfusion injury due to impaired microvascular integrity,embolisation of athero-thrombotic debris and/or disrupted end-organ metabolism.MC-1 is an inves-tigational drug from Medicure,Inc.In preclinical models of ischaemia and ischaemia-reperfusion injury,treatment with MC-1 has demonstrated significant cardio-and neuroprotective effects.Although the pharmacological activity of MC-1 may involve multiple mechanisms,research suggests that at least part of the protective effect may be mediated through its actions on purinergic receptors.Early clinical experience with MC-1 also appears to be promising:in a recent Phase II evaluation,treatment with MC-1 was associated with a statistically significant reduction in periprocedural infarct size(as measured by area under the curve creatine kinase-myocardial band)among high-risk patients undergoing elective percutaneous coronary intervention.Based on these findings,larger,randomised trials to confirm the safety and efficacy of MC-1 in the setting of coronary artery revascularisation with coronary artery bypass graft,acute coronary syndromes and stroke are ongoing or in development.These forthcoming evaluations should clarify the safety and efficacy of MC-1 and improve the understanding regarding its potential therapeutic role in a variety of clinical settings and indications.
机译:尽管机械性再灌注疗法(如经皮冠状动脉介入治疗和冠状动脉搭桥术)具有总体功效,但可以降低与急性缺血综合征相关的发病率和死亡率,但许多治疗的患者由于微血管完整性受损而发展为缺血再灌注损伤MC-1是来自Medicure,Inc.的研究药物。在缺血和缺血再灌注损伤的临床前模型中,MC-1的治疗已证明可显着改善心脏疾病。 -和神经保护作用。尽管MC-1的药理活性可能涉及多种机制,但研究表明,至少部分保护作用可能是通过其对嘌呤能受体的作用而介导的。早期的MC-1临床经验似乎也很有希望:在最近的II期评估中,MC-1的治疗与统计学上显着的降低相关在进行选择性经皮冠状动脉介入治疗的高危患者中,围手术期梗死面积(以曲线肌酸激酶-心肌带下面积测量)为基础。基于这些发现,进行了更大范围的随机试验,以证实MC-1的安全性和有效性通过冠状动脉搭桥术进行冠状动脉血运重建的设置,急性冠脉综合征和中风的研究正在进行中或正在发展中。这些即将进行的评估应阐明MC-1的安全性和有效性,并增进对MC-1在各种临床中潜在治疗作用的了解设置和指示。

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