Single Residue Variation in Skeletal Muscle Myosin Enables Direct and Selective Drug Targeting for Spasticity and Muscle StiffnessTherapeutic muscle relaxation is currently achieved pharmacologically via indirect mechanisms by modulation of the nervous system. Selective targeting of skeletal muscle has not been possible because myosin isoforms in skeletal muscle and the heart are structurally very similar. Using a rational, structure-based approach, Gyimesi et al. design a small-molecule muscle relaxant that specifically inhibits the skeletal, but not the cardiac, myosin 2 isoform. With their new drug candidate, they show how spasticity and muscle stiffness might be relieved pharmacologically without cardiac or nervous system side effects.Therapeutic muscle relaxation is currently achieved pharmacologically via indirect mechanisms by modulation of the nervous system. Selective targeting of skeletal muscle has not been possible because myosin isoforms in skeletal muscle and the heart are structurally very similar. Using a rational, structure-based approach, Gyimesi et al. design a small-molecule muscle relaxant that specifically inhibits the skeletal, but not the cardiac, myosin 2 isoform. With their new drug candidate, they show how spasticity and muscle stiffness might be relieved pharmacologically without cardiac or nervous system side effects.Máté Gyimesi, Ádám I. Horváth, Demeter Túrós, Sharad Kumar Suthar, Máté Pénzes, Csilla Kurdi, Louise Canon, Carlos Kikuti, Kathleen M. Ruppel, Darshan V. Trivedi, James A. Spudich, István Lőrincz, Anna Á. Rauscher, Mihály Kovács, Endre Pál, Sámuel Komoly, Anne Houdusse, András Málnási-Csizmadiahttps://secure.jbs.elsevierhealth.com/action/getSharedSiteSession?redirect=https%3A%2F%2Fwww.cell.com%2Fcell%2Ffulltext%2FS0092-8674%2820%2931138-7%3Frss%3Dyes&rc=0http://www.cell.com/cell/inpress.rssCellCell RSS feed.Wireless News CampaignOctober 9, 2020

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