Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was identified as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models by Che-Hong Chen and colleagues from the Stanford University (USA), using an unbiased proteomic search. The research team wanted to find a drug that limits the severity of ischemia-induced cardiac damage occurring after a myocardial infarction or certain cardiac surgical procedures.

The scientists performed a high-throughput screen which led to a small-molecule activator of ALDH2 (Alda-1). When rats were treated with the substance before an ischemic event, the infarct size was decreased by 60%. Alda-1 has an inhibitory effect on the synthesis of cytotoxic aldehydes. This is is assumed to be the main activity of the drug.

In in vitro studies, Alda-1 showed exceptionally effective activation of ALDH2*2, an inactive form of ALDH2. The associated mutation occurs in 40% of East Asian patient cohorts.

The ALDH2 enhancer might be suitable for patients who are at risk of cardiac ischemia, such as during coronary bypass surgery.

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