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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-02 DOI:10.1016/j.isci.2025.112335

Anas Odeh , Mor Sela , Shelly Zaffryar-Eilot , Ariel Shemesh , Maher Abu Saleh , Ido Mizrahi , Lavi Coren , Avi Schroeder , Peleg Hasson

引用次数: 0

Abstract

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.

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用于改善和治疗 DMD 的抗纤维化、促进肌肉生长的抗体药物共轭物

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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