Deflazacort Scientific Communication Platform

Transcript:Deflazacort Scientific Communication Platform:
Deflazacort Scientific Communication Platform ENTER ► Scientific Communication Platform Pillars Pillar 1: Pathophysiology of Dystrophinopathy Pillar 2: Early Screening, Diagnosis, and Treatment Pillar 3: Dystrophinopathy Treatment and Unmet Need Pillar 4: Importance of Continuous Corticosteroid Therapy Pillar 5: Deflazacort Molecular Profile and Efficacy Pillar 6: Deflazacort Safety and Tolerability 2 Scientific Communication Platform Pillars Pillar 1: Pathophysiology of Dystrophinopathy Pillar 2: Early Screening, Diagnosis, and Treatment Pillar 3: Dystrophinopathy Treatment and Unmet Need Pillar 4: Importance of Continuous Corticosteroid Therapy Pillar 5: Deflazacort Molecular Profile and Efficacy Pillar 6: Deflazacort Safety and Tolerability 3 Pillar 1: Pathophysiology of Dystrophinopathy Strategic Driver Mutations in the dystrophin gene disrupt the structure and stability of all muscles, leading to a progressive and irreversible decline in physical function that begins in infancy and leads to early death. 4 Scientific Messages Dystrophin is critical to the structure and stability of all muscles, including skeletal, cardiac, and respiratory muscles. Dystrophinopathies are rare, progressive, and incurable diseases caused by mutations in the dystrophin gene. Absent or dysfunctional dystrophin protein leads to irreversible degeneration of muscle cells throughout the body and is associated with inflammation. As dystrophinopathy progresses, loss of earlier milestones is predictive of future declines. Patients may experience severe orthopedic, respiratory, and cardiac complications, and ultimately, early death due to disease progression. 1. Pathophysiology of Dystrophinopathy Pillar 1: Scientific Statements 5 Scientific Message 1 Dystrophin is critical to the structure and stability of all muscles, including skeletal, cardiac, and respiratory muscles. Dystrophin is a large structural protein that links the internal cytoskeleton to the extracellular matrix as part of a large protein complex Dystrophin is a 472-kDa protein with key protein binding regions that include an amino-terminal domain, a central rod domain, a cysteine-rich domain, and the carboxyl-terminal domain The actin-binding amino terminal domain associates directly with the subsarcolemmal actin network The central rod domain forms a flexible linker between the amino- and carboxyl-terminal domains, and can bind with membrane phospholipids, the actin, microtubule, and intermediate filament cytoskeletons, as well as with β-dystroglycan, which anchors dystrophin at the sarcolemma (the sheath that covers the fibers of the skeletal muscle) 1.1.1 Gao 2015 1 3 2 4 5 Scientific message: 1. Pathophysiology of Dystrophinopathy Pillar 1: Scientific Statements 6 Scientific Message 1 Dystrophin is critical to the structure and stability of all muscles, including skeletal, cardiac, and respiratory muscles. Dystrophin provides stability and structure to the muscle