FAILED REGENERATION IN THE MUSCULAR DYSTROPHIES: INFLAMMATION, FIBROSIS AND FAT

 描述(申请人提供)：MDCRC围绕通过抑制肌肉纤维化和限制肌肉的脂肪替代来改善多种类型的肌营养不良症的肌肉再生，从而改善骨骼肌修复和保护心脏功能这一中心主题而组织。建议进行相互作用和协作的研究，以解决肌肉纤维化和脂肪沉积的发生机制。项目1的重点是了解导致炎症、纤维化和脂肪沉积的途径和细胞类型。项目1将评估一些潜在的治疗方法，利用一种令人兴奋的DMD新小鼠模型，即DBA背景下的MDX小鼠，这可能会极大地加速成功的药物转译。项目2的重点是确定和表征心脏病的修饰物，在许多情况下，这些修饰物也将是骨骼肌疾病的修饰物。项目3将深入了解LTBP4和骨桥蛋白的基因变异如何影响DMD患者心脏、呼吸肌和腿部肌肉疾病的成像生物标记物。为此，项目3将开发用于监测呼吸肌疾病进展的MRI/MRS方案。

 DESCRIPTION (provided by applicant): This MDCRC is organized around the central theme of improving muscle regeneration in a number of types of muscular dystrophy by inhibiting fibrosis and limiting fatty replacement of muscle, thus improving skeletal muscle repair and preserving cardiac function. Interacting and collaborative studies are proposed to address by what mechanisms muscle fibrosis and fat deposition occur. Project 1 is focused on understanding the pathways and cell types that contribute to inflammation, fibrosis, and fatty deposition. Project 1 will evaluate a number of potential therapeutics, utilizing an exciting new mouse model of DMD, the mdx mouse on the DBA background, which may greatly accelerate successful drug translation. Project 2 is focused on identifying and characterizing modifiers of cardiac disease, which in many cases will be modifiers of skeletal muscle disease as well. Project 3 will gain insights into how genetic variations in LTBP4 and Osteopontin impact imaging biomarkers of disease in the heart, respiratory muscles, and leg muscles of DMD patients. In doing so, Project 3 will develop MRI/MRS protocols for monitoring disease progression in the respiratory muscles.