Joshua J Todd, Tokunbor A Lawal, Irene C Chrismer, Angela Kokkinis, Christopher Grunseich, Minal S Jain, Melissa R Waite, Victoria Biancavilla, Shavonne Pocock, Kia Brooks, Christopher J Mendoza, Gina Norato, Ken Cheung, Willa Riekhof, Pooja Varma, Claudia Colina-Prisco, Magalie Emile-Backer, Katherine G Meilleur, Andrew R Marks, Yael Webb, Eugene E Marcantonio, A Reghan Foley, Carsten G Bönnemann, Payam Mohassel
BACKGROUND: RYR1 -related myopathies ( RYR1 -RM) are caused by pathogenic variants in the RYR1 gene which encodes the type 1 ryanodine receptor (RyR1). RyR1 is the sarcoplasmic reticulum (SR) calcium release channel that mediates excitation-contraction coupling in skeletal muscle. RyR1 sub-conductance, SR calcium leak, reduced RyR1 expression, and oxidative stress often contribute to RYR1 -RM pathogenesis. Loss of RyR1-calstabin1 association, SR calcium leak, and increased RyR1 open probability were observed in 17 RYR1 -RM patient skeletal muscle biopsies and improved following ex vivo treatment with Rycal compounds...
February 2024: EClinicalMedicine