MC-1 (pyridoxal 5'-phosphate): novel therapeutic applications to reduce ischaemic injury.
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 atherothrombotic debris and/or disrupted end-organ metabolism. MC-1 is an investigational 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.
Kandzari
David E
DE
Duke Clinical Research Institute, Durham, NC 27705, USA. kandz002@mc.duke.edu
Dery
Jean-Pierre
JP
Armstrong
Paul W
PW
Douglas
Deborah A
DA
Zettler
Marjorie E
ME
Hidinger
G Karl-Gunnar
GK
Friesen
Albert D
AD
Harrington
Robert A
RA
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011732:Pyridoxal Phosphate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D011732:Pyridoxal Phosphate