FRRB Project 1731651 - Chondroitin sulfate proteoglycan-4, secreted by a binding imbalance between SP1 and NF-kB on CHST11 gene, triggers sympathetic cardiac denervation in Duchenne Muscular Dystrophy

Name and Surname of PI

Claudia Bearzi

Project Acronym


Project ID


Host Institution

Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico - Milan

Pathology of Interest

Duchenne Muscular Dystrophy

Research Area

Rare Diseases

Project Start Date

1 April 2021

Project End Date

31 March 2024


€ 600.000,00

Type of Project



Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by the degeneration of skeletal and cardiac muscles. DMD patients exhibit progressive left ventricular dilation leading to dilated cardiomyopathy. We have shown, in a dystrophic mouse model, that sympathetic innervation of the heart is greatly reduced due to accumulation of extracellular matrix proteins (ECM), including the proteoglycan CSPG4, known to inhibit the progression of the nerve endings. The project aims to restore the innervation, and therefore the performance of the heart in dystrophic pig model, by the genetic correction of the factors that determine the ECM alteration, the use of 3D bioprinting to study the role of the dystrophic ECM, and the development of a therapy based on engineered T lymphocytes (CAR-T) against CSPG4. These approaches could pave the way for a new concept of therapy by improving patients' life expectancy.