Cancer drug that inhibits porcupine enzyme could help hearts
Inside our bodies, compounds known as Wnt proteins are something of a double-edged sword. When functioning normally, they help with tissue regeneration, such as that which takes place in lining of our guts or at injury sites. When they go haywire however, they can lead to cancer. Researchers from the University of Texas Southwestern (UTSW) were examining the role these compounds have in cancer when they made a serendipitous discovery just might help damaged hearts repair themselves.
Specifically, the researchers were looking at inhibiting an enzyme that stops Wnt proteins from being created. That enzyme is known as porcupine enzyme (PORCN) because fruit flies that lack the gene to produce it resemble the quill-covered mammal. While conducting testing on their enzyme inhibitor, the researchers saw some negative effects, but also a surprisingly positive one as well.
"We saw many predictable adverse effects – in bone and hair, for example – but one surprise was that the number of dividing cardiomyocytes (heart muscle cells) was slightly increased," said Dr. Lum, senior author of the paper, and a member of UTSW's Hamon Center for Regenerative Science and Medicine. "In addition to the intense interest in porcupine inhibitors as anticancer agents, this research shows that such agents could be useful in regenerative medicine."
To further explore this dual role of the inhibitor, they induced heart attacks in mice and then treated them with the compound. Sure enough, the hearts in the affected mice were able to pump blood twice as effectively as those left untreated after the heart attack. They also found that the compound reduced scarring in the heart.
This is especially significant because heart muscle cells don't regenerate like other cells in the body and, after cardiac arrest, the heart can be left permanently scarred and weakened. If the new compound could reverse part of that process, patients who suffer heart attacks could have a better prognosis. What's more, Lum said that the inhibitor could likely be administered for a short period of time after a heart attack to allow a patient to reap its benefits without incurring unpleasant side effects.
"We hope to advance a Porcn inhibitor into clinical testing as a regenerative agent for heart disease within the next year," he added.
The study findings were published online this week in Proceedings of the National Academy of Sciences.
Source: UT Southwestern
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