PRIORITY: cardio-laminoPathy: fRom pathomechanIsms tO peRsonalIzed TherapY | 2024

• Gisèle BONNE, Sorbonne Université, INSERM (France)
• Andrew LANDSTROM, Duke University School of Medicine (USA)

LMNA-related dilated cardiomyopathy (LMNA-DCM) is a severe and inherited disease caused by mutations in the LMNA gene. This gene provides instructions for making proteins called A-type Lamins (Lamins A/C), which help maintain the structure of the cell nucleus and play an important role in regulating chromatin organization, gene expression, and cytoskeletal organization by interacting with numerous other proteins. There is no effective treatment for LMNA-DCM because we do not fully understand the disease’s underlying mechanisms. Therefore, the proposed PRIORITY (cardio-laminoPathy: fRom pathomechanIsms tO peRsonalIzed TherapY) network aims to fill this knowledge gap and develop personalized, disease-modifying therapies.

PRIORITY has three main Aims. Aim 1 investigates the clinical and genetic signs associated with LMNA-DCM, identifying factors to understand what factors affect the severity and progression of the disease. Aim 2 pursues the underlying disease mechanism(s) contributing to LMNA-related DCM, uncovering the complex cellular and molecular processes underlying the pathogenesis and disease progression using state-of-the-art technologies. Aim 3 develops mechanism-based therapies for LMNA-related DCM by leveraging existing concepts and novel findings from Aim 2, potentially offering personalized therapeutic options for LMNA-DCM patients.

Our team comprises internationally renowned experts from prestigious European institutions (Sorbonne Université-Inserm, Amsterdam University, Maastricht University, University of Zurich, Paris-Cité University) and the USA (Duke, Cornell, and Stanford), along with early career investigators. We will partner with LMNAcardiac.org, a patient-led foundation, to ensure a patient-centered approach and to address the needs of those affected by LMNA-DCM. International collaborations and exchanges will offer unique interdisciplinary training opportunities for early career scientists in the network.

In conclusion, the PRIORITY project aims to understand the causes and progression of LMNA-DCM and develop personalized therapies. This research could significantly improve the management and outcomes of LMNA-DCM, ultimately benefiting those affected by the disease.