BHV-8000 is a novel, brain-penetrant, oral small molecule highly selective against the TYK2 and JAK1 enzymes within the JAK-STAT pathway, avoiding the safety liabilities of JAK2/3 inhibition. TYK2 and JAK1 signaling is essential to the mixed inflammatory response driving progression of many neuroinflammatory conditions. BHV-8000 is being explored as disease-modifying therapy in PD.

Administration of BHV-8000 at 10 and 30 mg/kg increased the movement distance of model animals in open-field by 36.8% and 61.4%, the time on rotarod by 14.8% and 64.4%, and the maximal force in grip strength test by 48.5% and 47.5%, respectively. Additionally, BHV-8000 administration mitigated microglial activation determined by reductions of Iba1+ microglia, and promoted neuronal survival indicated by increased counts of TH+ neurons in parallel with reduced IL-6 expression.

BHV-8000 administration reduced abnormal locomotor behavior deficits, inhibited inflammatory microglial activation, and protected against neurodegeneration in α-Syn overexpressing mice. These results support the potential of JAK1/TYK2 inhibition with BHV-8000 as a novel, disease modifying approach to the treatment of PD and other neuroinflammatory and neurodegenerative diseases.