Long-Term Dystrophin Replacement Therapy in Duchenne Muscular Dystrophy Causes Cardiac Inflammation.

Micro-dystrophin replacement gene therapy is currently under clinical trials in Duchenne muscular dystrophy (DMD) patients. However, recent adverse cardiac events has led to serious concerns about this therapeutic intervention. We studied the long-term effect of dystrophin replacement strategies in a severe model of DMD (mdx; utrophinmice). Although micro-dystrophin remarkably improved survival and cardiac function after 1 year of treatment, we were able to reveal an increased septum thickness, which is the result of cardiac inflammation. Our data warrant consideration that micro-dystrophin replacement therapy may be associated with cardiac inflammation and opens up perspectives for understanding the consequences of using this approach in DMD patients.