Over the past year, significant progress has been made within the international LMNA-331 research program, focusing on individuals carrying the LMNA R331Q variant. This inherited form of cardiomyopathy can vary greatly in severity—even among members of the same family—ranging from mild symptoms to severe arrhythmias and advanced heart failure.
What has been achieved?
Thanks to the commitment of participating families and supporters, the LMNA-331 project has grown into the largest biological LMNA-331 study worldwide. Researchers have successfully generated patient-derived stem cell lines from both European and U.S. carriers and differentiated them into chamber-specific heart cells, representing both atrial and ventricular cardiomyocytes.
This distinction is crucial, as LMNA-related disease often begins in the atria (for example with atrial fibrillation) and later progresses to the ventricles, where life-threatening rhythm disorders and heart failure may develop. The ability to study these differences in the laboratory represents a major scientific milestone.
In parallel, advanced genetic and epigenetic analyses are underway, alongside experiments that expose heart cells to controlled mechanical, metabolic, and oxidative stress. These studies aim to uncover why the same LMNA mutation can lead to very different clinical outcomes across individuals.
What comes next?
In the upcoming phase, the research will expand further using:
- Advanced 2D and 3D engineered “mini-heart” models
- Detailed analysis of electrical conduction, contractile force, and nuclear mechanics
- Mapping of molecular signaling pathways and gene activity
- Development of a mechanobiology-based risk prediction model, with the long-term goal of supporting personalized guidance on disease progression, physical activity, and treatment strategies
This unique and integrated approach has the potential to improve risk stratification, enable earlier intervention, and ultimately prevent life-threatening cardiac events in LMNA-related cardiomyopathy.
Call to action: participate and support
To continue this research at full speed, additional funding and community involvement are essential. There are several ways to contribute:
- Support the research through financial contributions
- Share this initiative within your personal and professional networks
- Express interest in participating or supporting the project as a donor or collaborator
Together—with families, researchers, and the broader LMNA community—we are building the knowledge needed to improve outcomes and quality of life for people living with LMNA-related heart disease.
Together, we can make a real difference.