Fig. 1.

Timeline of significant discoveries/milestones in the evolution of RYR1-RD. 1900s to present: In the twentieth century, congenital myopathy diagnoses were based primarily on muscle biopsy histopathologic features. Advancements in next-generation sequencing enabled more precise identification of RYR1-related phenotypes. Solving of the RyR1 structure at near-atomic resolution provided valuable insight into RyR1 channel function and disease mechanisms. These advances paved the way for the first RYR1-RM clinical trial completed in 2018 and the Phase 1 Rycal trial which began enrolling participants in 2020