Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee 53226, WI, USA.
Department of Biomedical Engineering, University of Florida, Gainesville 32607, FL, USA.
Hum Mol Genet. 2018 Feb 15;27(4):638-648. doi: 10.1093/hmg/ddx431.
Nemaline myopathy (NM) is a heterogeneous congenital skeletal muscle disease with cytoplasmic rod-like structures (nemaline bodies) in muscle tissue. While weakness in NM is related to contractile abnormalities, myofiber smallness is an additional abnormality in NM that may be treatable. We evaluated the effects of mRK35 (a myostatin inhibitor developed by Pfizer) treatment in the TgACTA1D286G mouse model of NM. mRK35 induced skeletal muscle growth that led to significant increases in animal bodyweight, forelimb grip strength and muscle fiber force, although it should be noted that animal weight and forelimb grip strength in untreated TgACTA1D286G mice was not different from controls. Treatment was also associated with an increase in the number of tubular aggregates found in skeletal muscle. These findings suggest that myostatin inhibition may be useful in promoting muscle growth and strength in Acta1-mutant muscle, while also further establishing the relationship between low levels of myostatin and tubular aggregate formation.
先天性肌纤维病是一种异质性的先天性骨骼肌疾病，在肌肉组织中有细胞质杆状结构（肌纤维）。虽然 NM 的无力与收缩异常有关，但肌纤维细小是 NM 的另一种异常，可能是可治疗的。我们评估了 mRK35（辉瑞公司开发的肌肉生长抑制素抑制剂）在 NM 的 TgACTA1D286G 小鼠模型中的治疗效果。mRK35 诱导骨骼肌生长，导致动物体重、前肢握力和肌肉纤维力量显著增加，尽管应该注意的是，未经治疗的 TgACTA1D286G 小鼠的体重和前肢握力与对照组没有区别。治疗还与骨骼肌肉中管状聚集物数量的增加有关。这些发现表明，肌肉生长抑制素抑制可能有助于促进 Acta1 突变肌的肌肉生长和力量，同时进一步建立肌肉生长抑制素水平低与管状聚集物形成之间的关系。
