Advancing Gene Therapies and Novel Treatment Strategies for Infiltrative Cardiomyopathies: A Comprehensive Review of Targeted Interventions.

Abstract

Recent progress in unraveling the molecular mechanisms of infiltrative Cardiomyopathies (CMPs) has created exciting opportunities for targeted therapies. These conditions, which include cardiac amyloidosis, sarcoidosis, Danon disease, Fabry disease, Mucopolysaccharidoses (MPS), and cardiac oxalosis, significantly impair cardiac function through complex pathogenic mechanisms. In cardiac amyloidosis, the accumulation of misfolded proteins into fibrillary amyloids disrupts myocardial structure, leading to inflammation, oxidative stress, and apoptosis. New treatments such as Antisense Oligonucleotides [ASOs], small interfering RNA [siRNA], and monoclonal antibodies have shown promising results in preclinical and clinical settings for managing amyloid deposition. Gene editing technologies, particularly CRISPR-Cas9, also have significant potential to deliver lasting therapeutic benefits by precisely correcting pathogenic mutations. Furthermore, managing Fabry disease with Enzyme Replacement Therapies [ERT] and chaperone molecules has improved cardiac outcomes; however, challenges remain in advanced stages due to ongoing myocardial involvement. Immunomodulatory strategies and innovative antibody-based therapies targeting pathological protein aggregates represent groundbreaking approaches that have shown efficacy in preclinical and earlyphase clinical trials. Despite these advancements, challenges remain, including the efficiency of drug delivery, possible off-target effects, and inconsistent clinical responses among different patient groups. Future research should focus on improving these therapies to increase their specificity and safety, ultimately enhancing patient outcomes and quality of life in infiltrative cardiomyopathies.