How do we help eliminate PLN from the world? Patients, doctors and researchers are challenging third-year students to better understand this inherited heart muscle disease. And to come up with research proposals that bring a therapy closer. “I am flabbergasted. These are great potential solutions.”
Wouter stands in front of a lecture hall of third-year biomedical science students. Ten years ago, he was a student himself: he was in rooms, playing sports, going to the pub. Until, at twenty-two, he went into cardiac arrest while playing field hockey. Twenty minutes his resuscitation lasted. “I felt the shocks from the defibrillator. How the air was forced out of my lungs by the chest compressions. You don’t want to go through something like that.”
There is dead silence in the lecture hall. Wouter’s story comes across clearly to the students. Wouter was diagnosed with PLN, an inherited heart muscle disease. His heart was deteriorating, losing more and more pumping power. And that, while he was young and wanted to graduate, wanted a girlfriend, a house, children. But how do you do that, when you don’t have the energy for the pub and are too tired for festivals? Fortunately, there was Tinder, he explains with a wink. “I wiped myself silly.”
Wouter relates his talk on PLN to a new teaching format devised by associate professor and head of the pathology research laboratory Niels Bovenschen. Niels brings together patients, (treating) medical specialists and researchers to share their knowledge and experience with undergraduate students in the pathology course. The intention is for the students to spend a month after this lecture thinking about possible experiments to further investigate PLN. Niels: “The idea is that with the best proposals we can do additional research on this misunderstood disease, research that otherwise would not happen. The goal is to better understand the nature of the disease and to find starting points for a therapy.”
Wouter was treated at the UMC Utrecht last year and received a support heart, a mechanical pump that supports the function of his left ventricle. After that, things slowly went back uphill. “I have been living with PLN for ten years now. The disease runs in the family, but fortunately our son Bram does not have PLN. So I have not passed on the disease, within my family it stops here. I want that for many more people.”
That is also the mission of Pieter, another PLN patient. He had just left abroad to build his business internationally when his heart went wrong. That night totally changed his life. Hospitalization, four and a half years of a support heart, paralysis in his legs. “At the end I could only stumble behind a walker,” he said. Until he received a heart transplant at UMC Utrecht. Now he has set up the PLN Genetic Heart Disease Foundation and is trying to eradicate PLN from the world once and for all. In the lecture hall, Pieter also has a clear message for the students: “Enjoy every day! And please help us find a solution to this rotten disease.”
Cardiologist Nicholas de Jonge treated Wouter. He explained that this heart muscle disease is all about predisposition, mutations in your DNA. “PLN stands for phospholamban, which is a small protein for calcium in the cell. If something is wrong in this PLN protein, then something goes wrong in the calcium metabolism. We don’t fully understand this process yet, we do know that it has major consequences cardiologically.” There is currently no cure, which is why PLN patients like Pieter and Wouter usually rely on a support heart and eventually a heart transplant. “Rather, we are doing more research to completely eradicate PLN.”
Professor of clinical genetics Peter van Tintelen studies the heredity of heart disease. He noticed that Wouter and Pieter themselves were severely affected, but that other family members with the mutation were less severely affected. “This hereditary disease can be very variable. Fortunately, we have found nearly 1,000 carriers of PLN. That is unique and now gives us the opportunity to find out what factors contribute to the development of this disease.”
Pathologist Aryan Vink conducted tissue research. “We saw that a large part of Wouter’s heart muscle had been replaced by fat cells and connective tissue. That’s not supposed to happen, something like that causes arrhythmias much faster and the pump function decreases. We also found inflammatory cells. Could there be some kind of immune disease? And we saw accumulations of the protein PLN in the heart muscle cells. It remains a mystery why this PLN accumulation occurs around the nucleus of some heart muscle cells.”
Professor of cardiology Pieter Doevendans says a lot of PLN research is currently being done. “A solution for this hereditary heart muscle disease is attainable and we will find it. We are working with other hospitals around the world on research to make this happen. In the blood of PLN carriers, we can look for biomarkers: signaling agents that can put us on the trail of when the disease starts or DNA testing to see if there might be other mutations. We also make heart muscle tissue from human materials, which we can then study. Because there are still many questions. Why do you sometimes get sick so late? And do we actually need the PLN protein? How strong should the treatment be?”
Student Judy is triggered, that morning in the lecture hall: “We were quite overwhelmed by Wouter’s intense story. To be confronted with such an illness at such a young age, that really gets to you. This motivates us enormously to find a solution.” Together with 95 other bachelor students from the pathology course, Judy will form the think tank that will work with all the input. In 16 groups of six, they will think about solutions and possible experiments to investigate the PLN riddle. They will have a month to come up with concrete research proposals.
When principal investigator Toon van Veen sees the pile of research proposals a month later, he is completely flabbergasted. “These are great potential solutions. We hadn’t even thought of some of the ideas ourselves!” The winners are Judy and her groupmates Soete, Cecile, Freek, Isabelle and Michael. Judy explains their proposal: “In PLN disease, a kind of clumps of mutated PLN protein are present in the heart muscle cells, which are believed to contribute to the symptoms of the disease. We propose to clean up these clumps with metformin. This is an existing drug that from research appears successful against similar protein clumps in heart muscle disease caused by diabetes.”
Initiator Niels: “If this works, you can bring the drug to the clinic and thus to the PLN patient very quickly.” For the students, the Pathology course is over. But it doesn’t stop here. The course bridges to the new laboratory course Experimental Translational Medicine, which Niels coordinates. In this undergraduate course, which starts in April, eight biomedical science students and eight medical students will work together with UMC Utrecht (medical) researchers to actually carry out the winning proposal. This will take place in the Bachelor Research Hub, a new laboratory for undergraduate students, right in the middle between the research labs and the clinic at UMC Utrecht. This cuts both ways. Role models inspire and motivate the students, and the students help the researchers and medical specialists make patients better. In any case, Judy is eager to participate in this.
