Novel Heart Attack Therapy: Caspase Inhibition Prior to Repurfusion

OPPORTUNITY

Preventing heart muscle death (infarction) during a heart attack is an important goal of treatment. To this end, patients typically receive platelet inhibitors and early opening of the thrombosed artery (reperfusion), both of which aim to reduce heart muscle loss. This treatment has lowered, but not eliminated, mortality and morbidity in these patients. Recent work in this field, including clinical trials, focused on “conditioning” interventions have failed to improve outcomes, presumably because they protect by the same mechanism as the platelet inhibitors. Therefore, there is still an unmet need for a therapy that adds to the protective effect of platelet inhibitors, rather than simply duplicating it.

 

BREAKTHROUGH IN TREATMENT OF MYOCARDIAL INFARCTION

Researchers at the University of South Alabama discovered that caspases, key enzymes in inflammation, also contribute to death of heart muscle during a simulated heart attack. In rat hearts, inhibiting a particular caspase with a highly selective caspase inhibitor greatly reduces infarct by a magnitude similar to that reported when using platelet inhibitors (standard of care). In rats receiving a combination treatment of both a platelet inhibitor (standard of care) and the caspase inhibitor administered prior to reperfusion, an additive reduction in infarct size is observed. This implicates caspases as a causative component of cell death in myocardial infarction, against which the platelet inhibitors do not protect. Thus, we believe that the use of the highly specific caspase inhibitor offers additional clinical benefit to patients receiving treatment for acute myocardial infarction.

 

COMPETITIVE ADVANTAGES

•  Novel use of existing compound

•  Reduction of infarct size when used in combination with a platelet inhibitor

•  Highest degree of cardioprotection observed in a rodent myocardial infarction model

•  Treatment effective when initiated 60-minutes after coronary occlusion

•  Infarct size smaller and contractile function of the heart preserved following treatment

 

INTELLECTUAL PROPERTY STATUS

Patent filed

 

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