Anti-fibrotic, muscle-promoting antibody-drug conjugates for the improvement and treatment of DMD

Fibrosis, characterized by the deposition of excess and disorganized extracellular matrix (ECM), is a key pathological hallmark of multiple diseases, including Duchenne muscular dystrophy (DMD). Aiming to inhibit fibrosis progression, we generated an antibody-drug conjugate (ADC) that delivers an innovative small molecule conjugate to inhibit the ECM-modifying enzyme Lysyl oxidase (LOX) specifically in fibrotic lesions by targeting M2 macrophages. Administration of the ADC to mdx mice, the murine model of DMD, results in ADC accumulation in fibrotic muscles without affecting healthy tissues. Long-term ADC treatments of adult mdx mice lead to inhibition of the fibrotic process and to significant improvement of cardiac and skeletal muscle function. Our study demonstrates that targeted inhibition of LOX-dependent fibrotic diseases, such as DMD, facilitates improved outcomes for muscular dystrophies.