Long-term human IgG treatment improves heart and muscle function in a mouse model of Duchenne muscular dystrophy.

摘要: BACKGROUND Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutations in the dystrophin gene, which leads to structural instability of dystrophin-glycoprotein-complex with subsequent muscle degeneration. In addition, inflammation has been implicated progression and therapeutically addressed glucocorticosteroids. These have numerous adverse effects. Treatment human immunoglobulin G (IgG) improved clinical para-clinical parameters early phase well-established mdx mouse model. The aim present study was confirm efficacy IgG long-term pre-clinical mice. METHODS (2 g/kg body weight) or NaCl solution as control administered monthly over 18 months intraperitoneal injection mice beginning at 3 weeks age. Several outcome measures including endurance, strength, echocardiography were assessed. After months, animals sacrificed, blood collected for analysis, samples obtained ex vivo contraction tests, quantitative PCR, histology. RESULTS significantly daily voluntary running performance (1.9 m more total distance, P < 0.0001) slowed decrease grip strength 0.1 mN, (P = 0.018). reduced fatigability diaphragm (improved ratio maximum force 0.09 ± 0.04, 0.044), but specific tetanic remained unchanged test. Cardiac function better after IgG, especially fractional area shortening 0.012). results accompanied reduction cardiac fibrosis infiltration T cells 0.0002) macrophages 0.0027). treatment resulted significant ≤ 0.036) diaphragm, gastrocnemius, quadriceps, similar trend tibialis anterior 0.045) anterior, well myopathic changes reflected central nuclear index quadriceps 0.002 all). CONCLUSIONS underscores importance an inflammatory contribution DMD. data demonstrate mouse. tolerated humans could preferentially complement gene therapy call trial