A cancer drug with unique heart regenerative potential
Every once in a while, the journey to drug discovery takes an unexpected detour. An example of this is a recent UT Southwestern effort, in which anti-cancer research may someday help patients recover after a heart attack.
An anti-cancer agent in development – specifically a porcupine (Porcn) enzyme inhibitor – has been found to promote regeneration of damaged heart muscle. Because of the heart’s inability to repair itself, damage caused by a heart attack leads to permanent scarring that frequently results in serious weakening of the heart, known as heart failure.
For years, biomedical scientists in the Harold C. Simmons Comprehensive Cancer Center and the Hamon Center for Regenerative Science and Medicine have worked to develop a cancer drug targeting Wnt signaling molecules. These molecules, crucial for tissue regeneration, also frequently contribute to cancer. Essential to the production of Wnt proteins in humans is the porcupine enzyme, so named because fruit fly embryos lacking this gene resemble a porcupine.
In testing the porcupine inhibitor researchers developed, they noted a curiosity – that the number of dividing heart muscle cells was slightly increased, generating a new focus on whether such agents could be useful in regenerative medicine.
“Our lab has been studying heart repair for several years, and it was striking to see that administration of a Wnt inhibitor significantly improved heart function following a heart attack in mice,” said Dr. Rhonda Bassel-Duby, Professor of Molecular Biology and Associate Director of the Hamon Center, who collaborated on the investigation with Dr. Lawrence Lum, formerly an Associate Professor of Cell Biology and Associate Director of Basic Research at the Simmons Cancer Center.
Based on their results, the researchers induced heart attacks in mice and then treated them with a porcupine inhibitor. Their hearts’ ability to pump blood improved by nearly twofold compared with untreated rodents.
The study findings were published in Proceedings of the National Academy of Sciences.
Importantly, in addition to the improved pumping ability of hearts in the mice, the researchers noticed a reduction in fibrosis, or scarring in the hearts. Collagen-laden scarring that occurs following a heart attack can cause the heart to inappropriately increase in size, which in turn can lead to heart failure.