RYR1-related diseases patient-led international research workshop: Novel perspectives, treatments and interventions.

RYR1-related diseases (RYR1-RDs) encompass a wide spectrum of disease manifestations with limited available disease-modifying therapies. The RYR1-RD phenotypes include congenital myopathies of different histotypes often with early-onset muscle weakness, feeding difficulties, and respiratory insufficiency of varying severity. RYR1-RDs also include a group of episodic diseases such as exercise intolerance, exertional rhabdomyolysis, periodic paralysis, and malignant hyperthermia susceptibility. The RYR-1 Foundation hosted the second patient-led international research workshop focused on RYR1-RDs which was held on July 23rd-24th, 2025 in Pittsburg, Pennsylvania, USA that included a group of affected individuals, clinicians, and researchers to review the current status of research, and to evaluate high-priority areas for future research to enable development of therapeutics with direct involvement of affected individuals in the design and topics of this workshop. Identified high-priority areas were organized into six sessions: 1) Diagnosis and Genetics of RYR1-RDs, 2) Establishing Clinical Trial Readiness for RYR1-RDs, 3) Novel Insights into RYR1 Pathophysiology, 4) Disease Models and Translational Studies in RYR1-RD, 5) The Therapeutic Development Pipeline, and 6) Physical Therapy and Exercise in RYR1-RDs. Several novel disease models and novel DNA- and RNA-directed therapies were discussed. To establish clinical trial readiness, prospective natural history studies to optimize outcome measures and biomarkers with exploration of imaging modalities and wearable sensors are ongoing. This article provides a cohesive summary of the presentations that encompasses basic research from structural biology and preclinical models to clinical trials, and novel therapeutic development strategies for RYR1-RD as a comprehensive narrative for the neuromuscular and rare disease research audience.