Neurology

In vitro and mouse studies identified an indazole-based inhibitor of DYRK1A that could help treat Down syndrome in fetuses. Screening of a small molecule library in mouse neural stem cells identified a pyridinylindazole-based DYRK1A inhibitor that promoted cell growth, which is deficient in Down syndrome, with an IC₅₀ of 364 nM. In human fibroblasts from Down syndrome patients, the compound decreased disease-associated growth delays compared with vehicle. In healthy mouse dams pregnant with Down syndrome fetuses, the compound increased scores in spatial learning and memory tasks in the pups compared with vehicle. Next steps include testing the DYRK1A inhibitor in Parkinson's disease and other neurological indications.

ManRos Therapeutics S.A. has undisclosed DYRK1A inhibitors in preclinical testing for Alzheimer's disease and Down syndrome...