Researchers at UMC Groningen recently made a major breakthrough in their search for a treatment for the heart muscle disease PLN, a disease caused by an error or “mutation” in the PLN gene. In their scientific publication, they describe experiments with mice carrying the PLN mutation. On these mice, they tested the protein DWORF as a possible treatment and saw encouraging results: the mice lived longer and the disease was delayed.
What is PLN?
Before we look at this research in more detail, let us first explain what heart muscle disease PLN is and how it is caused by the PLN mutation. Every person has in his or her DNA a recipe for the PLN protein, called the PLN gene. This protein plays an important role in the cells of the heart, especially in calcium metabolism. Calcium is crucial for the heart because it helps the heart contract and pump blood through the body. In carriers of the PLN mutation, there is an error in the recipe for the PLN protein, resulting in a malformed protein that does not function properly.
This malformed PLN protein tends to clump together, causing accumulations, or aggregates, in the heart muscle cells. These accumulations can be harmful to cells, as we see in other diseases such as Alzheimer’s disease. In the PLN mutation, these accumulations likely lead to damage and eventually death of heart muscle cells. This then causes damage to the heart muscle, resulting in PLN cardiomyopathy, or the heart muscle disease PLN. This disease can be accompanied by cardiac arrhythmias and heart failure, both consequences of damage to the heart muscle.
DWORF: a small protein with influence
Now DWORF comes into the picture, a small protein that, like PLN, affects calcium metabolism in cardiac muscle cells, but with an opposite effect. It is thought that this protein could have a positive effect in the treatment of PLN. To test this idea, researchers in Groningen set up an experiment with mice. These mice were specially genetically modified to have the same PLN mutation as humans with the heart muscle disease PLN. This means that the hearts of these mice are similarly affected by the mutation and thus these mice also develop heart problems. The researchers examined what happens when they treat these “PLN mice” with additional DWORF protein.
The results were impressive: the mice with extra DWORF lived longer and suffered fewer heart problems. It seems that DWORF helped reduce the clumping of the misshapen PLN protein. This likely contributed to healthier heart muscle cells and thus a better functioning heart.
This groundbreaking research shows that new options are in development for the treatment of the heart muscle disease PLN. If DWORF works in humans as it did in the mice in this experiment, it could have major implications for patients with this disease. This research is an important step forward in understanding and treating the difficult and currently incurable heart muscle disease PLN.