Research suggests a new treatment strategy for heart patients

A new study conducted by researchers from the University of Copenhagen shows insights into a new mechanism involved in the progression of arrhythmogenic right ventricular cardiomyopathy (ARVC), according to a press release published by the institution.

Heart disease, known as ARVC, mostly affects adults and damages the myocardial, the heart's muscle wall. Over time, this illness causes a portion of the myocardium to deteriorate, raising the risk of arrhythmia and abrupt death.

It is also the reason behind heart failures occurring in young athletes. Half of all cases involving sudden cardiac arrest in athletes occurring during physical activity are thought to be caused by ARVC.

New insights on ARVC

"We have identified a previously unknown disease mechanism in ARVC, which adds a completely new layer of information that no one knew about," says Professor Alicia Lundby from the Department of Biomedical Sciences at the University of Copenhagen, and the leader of the research team that conducted the study.

The mentioned mechanism that has been discovered is a defect occurring in the nucleus deep inside the heart cells working for the contraction of the heart muscle. It causes a chain reaction and ultimately results in cell death.

The research team examined heart biopsies from healthy individuals and from patients who suffer from hereditary ARVC. Later on, they performed deep molecular profiling of the heart samples and detected the molecular variations between the hearts.

Based on the findings, researchers generated hypotheses about the causes of the disease, and then tested them on mice models and stem cell-derived heart muscle cells.

"Based on the new insights we obtained, we identified a molecule that may be able to slow down disease progression," adds Lundby.

Activating sirtuin-3

By activating a molecule called sirtuin-3, researchers found the progression of the disease could actually be slowed down. In this direction, they started to look for a molecule with the same function.

Researchers eventually found a compound named honokiol, which is a natural substance that derives from the bark and leaves of the tulip tree and has been used as a pain killer in traditional medicine in some parts of Asia

"When we tested honokiol on our mouse model, it really did slow down the development of the disease. The same happened in our stem cell-derived heart cells. We do not know if it works the same with humans, but the fact that we can confirm the effect in two different models makes it very interesting," says Alicia Lundby.

"It is really satisfying to take a project all the way from very basic science measurements, through interpretation of the results to coming up with a possible strategy to mitigate the disease progression and finally demonstrate that it works. To me, this is truly the essence of the type of research I am excited about, namely to shed light on the mechanisms behind heart disease such that we can propose novel treatment strategies," adds Lundby.

"Doing the types of studies we do, analyzing several thousands of proteins at a time, is challenging when trying to understand what the changes we measure actually mean. This part of the work requires delving into the scientific literature. So you read and read and read. And talk to colleagues, think and read some more. It is months of detective work. And it's both stimulating and frustrating at times. Because it is certainly not straightforward."

The researchers are now aiming to examine their findings thoroughly with a follow-up study they've launched.

"We believe our findings are significant, and we want to determine whether they can actually help patients. The next step for us is to determine whether the mechanism we identified is present in all ARVC patients," concludes Lundby.

The study was published in the journal Circulation.