Musculoskeletal

Mouse studies suggest inhibiting senescent cells could help treat age-related bone loss. In aged, transgenic mice expressing the senescence marker human CDKN2A, a tool compound that depletes CDKN2A-positive cells decreased the number of senescent osteoclasts and senescence markers in bone and increased spine trabecular bone microarchitecture, femur cortical thickness and bone strength compared with vehicle. In wild-type aged mice, a combination of senolytic agents -- Sprycel dasatinib plus quercetin -- decreased levels of CDKN2A and other senescence markers in bone and increased spine trabecular bone microarchitecture, femur cortical thickness, bone strength and other measures of bone growth. Also in the mice, Jakafi ruxolitinib -- an inhibitor of IL-6, plasminogen activator inhibitor 1 (SERPINE1; PAI1) and other components of the senescence-associated secretory phenotype (SASP) -- increased spine trabecular bone microarchitecture and bone strength of the femur. Next steps include testing Sprycel plus quercetin in pilot studies in humans.

Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co. Ltd. market the BCR-ABL tyrosine kinase (BCR-ABL)/Src inhibitor Sprycel for acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML) and have the compound in Phase II testing for pancreatic and breast cancers and Phase I testing for leukemia...