BioCentury
ARTICLE | Distillery Therapeutics

Neurology

August 23, 2018 3:47 PM UTC

In vitro and cell culture studies identified two thiazolidinedione-based dual inhibitors of tau-aggregation and GSK3B that could help treat AD. Chemical synthesis and in vitro testing in enzymatic activity assays of 35 thiazolidinedione analogs yielded two compounds that inhibited GSK3B with IC50 values of 0.89 and 4.93 μM. In vitro, one of the compounds decreased spontaneous and heparin-induced tau fibril formation compared with no treatment or vehicle, respectively. In a human neuroblastoma cell-based model of hyperphosphorylated tau-induced neurodegeneration, both compounds increased viability compared with no treatment. Next steps could include testing the compounds in animal models of AD.

Neurim Pharmaceuticals Ltd. has Neu-120, a selective uncompetitive NMDA receptor modulator and monoamine oxidase B (MAO-B) and GSK3B inhibitor, in Phase II testing to treat Parkinson’s disease...