Lamin A/C cardiomyopathy is a common genetic heart disease caused by a mutation, or error, in the Lamin gene. Lamin is a protein in the membrane that encloses the cell’s nucleus and is found in all cells.
"The symptoms for the disease can appear as early on as in one's 20s with heart arrhythmias. Unfortunately, these patients have a very poor prognosis," Kristina Haugaa, professor at the Institute of Clinical Medicine at the University of Oslo, says.
This genetic defect eventually leads to more severe heart arrhythmias and can lead to sudden cardiac death (SCD) and severe heart failure.
"Currently, there is no specific treatment approved for this form of heart disease. We use medications for heart failure and defibrillators. Some patients may require a cardiac transplantation," Haugaa says.
A strong transatlantic collaboration
Together with researchers from the University of Minnesota (UMN), Haugaa has been granted funding to advance our understanding of Lamin A/C cardiomyopathy.
The funds are granted from the Norwegian Centennial Chair Program Solicitation for Transatlantic Research (NOCC).
"This is a moderately funded study. However, this exciting pilot study will allow us to establish a strong transatlantic collaboration, with the potential of other funding opportunities in the future," Haugaa says.
The LaMinOs project is led by UMN's Assistant Professor Forum Kamdar, with Haugaa and postdoctoral fellow Nina Hasselberg participating from the University of Oslo.
The mechanisms behind cardiac fibrosis
The study has two main objectives. First and foremost, the researchers aim to advance our knowledge of the disease.
"Our goal is to identify targets for future treatments of the disease," Haugaa says.
The second objective is to understand the mechanisms behind cardiac fibrosis, which is the formation of scar tissue in the heart.
"Our hypothesis is that Lamin A/C mutations promote cardiac fibrosis," she states.
"When the heart muscle becomes scarred, there is a great risk for the patient to develop life-threatening arrhythmias. This can lead to sudden cardiac death. Furthermore, it can cause the patient to develop heart failure. We therefore aim to understand the mechanisms behind cardiac fibrosis," she elaborates.
Haugaa and her collaborators also want to identify early-stage biomarkers of cardiac fibrosis.
“Early detection would be beneficial to identify patients at risk for sudden cardiac death and heart failure," the professor says.
The researchers will combine basic and clinical research
The project applies a multi-faceted approach that combines basic mechanistic understanding and translational technologies at UMN, with clinical research and a large patient cohort at UiO.
Haugaa and colleagues have one of the largest international Lamin A/C patient cohorts, with more than 150 patients with this gene defect. This unique database with long term follow-up data is included in the study.
“We follow a big cohort of patients that can potentially participate in the study. The patient data will be sent to Minnesota where they will test the blood samples and cultivate cells from the blood so that it can transform into heart muscle cells. Subsequently, they will examine how the fibrosis occurs”, Haugaa explains.
The researcher believe that the project has the potential to enable the development of new treatments and non-invasive early detection methods, which will directly benefit patients.
Contributed to new European guidelines for the treatment of cardiomyopathies
At the end of August this year, new European guidelines were introduced for the treatment of cardiomyopathies, like Lamin A/C cardiomyopathy. Haugaa took part in the writing group and contributed as an author.
"It is a great honor to be included, and also to represent the University of Oslo, in the development of these new guidelines," the professor says.
The new guidelines are circulated throughout Europe and are also used in many other countries for the treatment of cardiomyopathies.
About the NOCC program
The Norwegian Centennial Chair Program Solicitation for Transatlantic Research (NOCC) was established to support transatlantic collaboration between the University of Minnesota, the Norwegian University of Life Sciences, and the University of Oslo.
The funding of the program is provided by the three universities to support research in a wide portfolio of topics that are of common strategic interest to all three partner universities.