Laminin-111 protein therapy enhances muscle regeneration and repair in the GRMD dog model of Duchenne muscular dystrophy
Laminin-111 protein therapy enhances muscle regeneration and repair in the GRMD dog model of Duchenne muscular dystrophy
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DOI：
10.1093/hmg/ddz086
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发表时间：
2019-08-15
影响因子：
3.5
通讯作者：
Burkin, Dean J.
中科院分区：
文献类型：
--
作者：
Barraza-Flores, Pamela;Fontelonga, Tatiana M.;Burkin, Dean J.
杜氏肌营养不良症（DMD）是一种毁灭性的X-连锁疾病，影响约1/5000的男性。DMD患者表现出进行性肌肉变性和虚弱，导致截肢和心肺衰竭的过早死亡。我们以前报道过，小鼠层粘连蛋白-111（msLam-111）蛋白可以减轻DMD mdx小鼠模型的肌肉病理，改善肌肉功能。在这项研究中，我们检查了msLam-111在DMD的金毛猎犬肌营养不良症（GRMD）狗模型中预防肌肉疾病进展的能力。将msLam-111蛋白注射到GRMD狗的颅胫肌隔室中，并评估肌肉强度和病理学。结果显示，在GRMD模型中，msLam-111治疗增加了肌纤维再生和修复，同时改善了肌肉力量并减少了肌肉纤维化。总之，这些发现支持层粘连蛋白-111可以作为治疗DMD的新型蛋白质疗法的想法。
Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting similar to 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.