Experimental Drug Limits Muscle Damage from Heart Attack

Small-Molecule Drug Blocks Oxidative Stress Signals

An experimental drug has shown great promise in limiting heart muscle damage from myocardial infarction by targeting a protein that plays a central role in the death of heart muscle cells. Tests on mice have revealed that the drug could markedly reduce heart injury from a heart attack.The small-molecule drug blocks the protein MAP4K4, which relays the oxidative stress signals that cause the death of heart muscle cells and damage to tissue.

Lead investigator Michael D. Schneider, from Imperial College in London, and his team report their findings in a paper that appears in the journal Cell Stem Cell. "There are no existing therapies that directly address the problem of muscle cell death,” Schneider says, “and this would be a revolution in the treatment of heart attacks." Schneider’s team grew heart tissue from human stem cells and developed a way of modeling a "heart attack in a dish" for testing the drug.

The stress signals that a heart attack induces in heart muscle also occur following blood flow restoration. While it is crucial to restore blood flow following a heart attack, there is also a need to add treatments that limit this "reperfusion injury."

Dr. Schneider and his team are the first to uncover the role of MAP4K4 in the process through which a heart attack, by inducing oxidative stress, kills heart muscle cells. In their investigation, they revealed that MAP4K4 is active in heart tissue of people with heart failure, and also in mice, following a heart attack.

The researchers hope that their findings will lead to an injection that doctors can give to people before they undergo balloon angioplasty to open a blocked artery following a heart attack. Another possibility is that such a drug could also help limit heart muscle damage from heart attacks in regions with no rapid access to treatments that restore blood flow. The researchers believe that because they tested the drug in a model that they had developed using human stem cells, it should stand a good chance of succeeding in human clinical trials.

Source: Medical News Today, March 11, 2019