Giusy Ciuffreda

Targeting fibrosis in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a critical outstanding clinical issue, as cardiac failure remains a leading cause of death despite advances in supportive care. This study evaluates the therapeutic efficacy of CSPG4-targeted chimeric antigen receptor (CAR) T cells in reducing cardiac fibrosis and improving heart function in a preclinical model of the disease. DMD is a progressive genetic disorder characterized by degeneration of skeletal and cardiac muscle. Cardiomyopathy, driven by fibrosis and chronic inflammation, is a leading contributor to mortality in affected patients. Proteoglycans such as CSPG4, critical regulators of extracellular matrix dynamics, are markedly overexpressed in dystrophic hearts and promote pathological remodeling. Current treatments do not adequately target the fibrotic and inflammatory processes underlying cardiac dysfunction. CSPG4-specific CAR-T cells were engineered and administered to dystrophic mice. Therapeutic efficacy was assessed through histological, molecular, and echocardiographic analyses evaluating cardiac fibrosis, inflammation, innervation, and overall function. Treatment with CSPG4 CAR-T cells preserved myocardial integrity, improved cardiac performance, and reduced both fibrosis and inflammatory markers. The therapy also restored cardiac innervation, indicating a reversal of neural remodeling commonly seen in muscular dystrophy-related cardiomyopathy. CSPG4-targeted CAR-T therapy offers a novel, cell-based strategy to mitigate cardiac remodeling in dystrophic hearts. By addressing core fibrotic and inflammatory drivers of disease, this approach represents a significant advancement in the development of precision immune therapies for muscular dystrophies and cardiovascular conditions.

Glioblastoma is a highly aggressive, infiltrative brain tumor of the central nervous system (CNS). Its extensive molecular and biochemical heterogenicity hinders the identification of reliable biomarkers and therapeutic targets, thereby making prognosis and existing therapy ineffective. In recent years, breakthroughs in the use of proteomics on a range of biological samples, such as plasma, cerebrospinal fluid (CSF), tissues, brain cells, and exosomes, represent a potential improvement to GBM investigations. Mass spectrometry-based approaches represent an important technique in the characterization of the tumoral proteome, for the identification of differentially expressed proteins, and for studying altered molecular pathways involved in tumor stages. Proteomics studies advance our knowledge about GBM pathogenesis, the discovery of reliable diagnostic and prognostic markers, and therapeutic approaches, also. In this context, for the effective application of proteomics on GBM, it is mandatory to develop a translational network by integrating hospitals, biobanks, and research institutions into a single network, to enable a collaborative approach across disciplines, thereby enabling rapid translation to clinical application of new proteomic insights. Today, high-quality biobanks play a key role in enabling collaborative, ethically compliant research, supporting the effective application of proteomics in glioblastoma studies and the translation of discoveries into clinical practice. This review explores current trends in proteomics and GBM research, highlighting how leveraging biobank infrastructure and fostering institutional cooperation can drive the development of targeted pilot projects to enhance the impact and effectiveness of glioblastoma research.