Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Hum Mol Genet. 2019 Aug 15;28(16):2686-2695. doi: 10.1093/hmg/ddz086.
Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce muscle pathology and improve muscle function in the mdx mouse model for DMD. In this study, we examined the ability of msLam-111 to prevent muscle disease progression in the golden retriever muscular dystrophy (GRMD) dog model of DMD. The msLam-111 protein was injected into the cranial tibial muscle compartment of GRMD dogs and muscle strength and pathology were assessed. The results showed that msLam-111 treatment increased muscle fiber regeneration and repair with improved muscle strength and reduced muscle fibrosis in the GRMD model. Together, these findings support the idea that Laminin-111 could serve as a novel protein therapy for the treatment of DMD.
杜氏肌营养不良症（DMD）是一种破坏性的 X 连锁疾病，影响约每 5000 名男性中的 1 名。DMD 患者表现出进行性肌肉退化和无力，导致行走能力丧失，并因心肺衰竭而过早死亡。我们之前报道过，小鼠层粘连蛋白-111（msLam-111）蛋白可以减少 mdx 小鼠模型中的肌肉病理学并改善肌肉功能。在这项研究中，我们研究了 msLam-111 预防 DMD 的金毛猎犬肌肉营养不良（GRMD）犬模型中肌肉疾病进展的能力。将 msLam-111 蛋白注入 GRMD 犬的颅胫骨肌隔室，并评估肌肉力量和病理学。结果表明，msLam-111 治疗可增加肌肉纤维再生和修复，改善肌肉力量并减少 GRMD 模型中的肌肉纤维化。总之，这些发现支持层粘连蛋白-111 可以作为一种新型的蛋白质治疗方法用于治疗 DMD。
