Polimi research on rare cardiomyopathy funded by telethon and cariplo

Study addresses role of mlip in lmna-cardiomyopathy in ipsc-based human 3d-cardiac models

Fondazione Cariplo and Fondazione Telethon have awarded over 2,700,000 euros to 12 projects involving 19 researchers in basic research in the Lombardy Region. The aim of the initiative is to understand genetic aspects and molecular mechanisms that are still largely unknown or poorly understood, but potentially useful for fostering the development of new therapies for rare diseases. 

Although the human genome has been fully sequenced, about one-third of human proteins have not yet been described. This portion of the genome still unexplored could help to clarify new physiological and pathological mechanisms and could represent a mine to discover new therapeutic pathways. In particular, the projects had to focus on the study of so-called Tdark targets, for which no information on structure, function and interaction with molecules and drugs is known. 

The project that involves us is the “Study of the role of MLIP in LMNA-Cardiomyopathy in iPSC-based human 3D-cardiac models “, conducted by researchers Marco Rasponi, of the Department of Electronics, Information and Bioengineering of the Politecnico di Milano, and Elisa Di Pasquale, of the CNR and IRCCS Humanitas Clinical Institute. 

LMNA- Cardiomyopathy is a form of inherited cardiomyopathy caused by mutations in the Lamin A/C encoding gene, LMNA. It is characterized by left ventricular dilatation and systolic dysfunctions, usually associated with various conduction abnormalities and arrhythmias, which manifest with variable penetrance and expressivity, leading to diverse patterns of clinical phenotypes. Mechanisms behind such clinical variability are still largely unknown. 

The project focuses on MLIP, a binding partner of Lamin A/C proteins, whose function in the heart is still largely unknown. Specifically, while deepening its physiological action in the heart, the goal is to determine whether MLIP plays a role in the pathogenesis of LMNA-cardiomyopathy (LMNA-CMP), as a “modifier” of disease, contributing to the clinical heterogeneity typical of the disease.  

From an experimental point of view, breakthrough technologies will be integrated, namely CRISPR/Cas9 system, induced pluripotent stem cells (iPSCs) and organs-on chip (mHeart), to generate 3D human cardiac microtissue models, in which functional and molecular roles will be comprehensively investigated. 

The project outputs will bring knowledge about the functional and molecular roles of MLIP in the onset and progression of LMNA-CMP, filling some gaps in the understanding of its clinical heterogeneity. In the long term, this increased knowledge could contribute to improve clinical management of patients

Life Sciences