Study Rationale: Tau aggregation is caused by hyperphosphorylation and misfolding of the Tau protein in the brain, leading to cellular dysfunction and neurodegeneration. Preclinical and clinical studies showed that inhibiting Tau aggregation reduces neurotoxicity and has the potential to prevent the spread of Parkinson’s Disease pathology.
Hypothesis: The Psy Therapeutics approach is to target Tau during the oligomer stage to prevent aggregation and block tau propagation.
Study Design: The objective of this project is to further evaluate PSY-055 and PSY-106 through initial in vitro and in vivo functional studies and select one for biochemical optimization for further preclinical studies. We will further characterize the primary biological effects of PSY-055 and PSY-106 in inhibiting tau protein aggregation through cellular models of aggregation and toxicity including synuclein A53T and LRRK2 G2019S mutations in vitro and characterize DMPK properties of the two compounds. Aim 2 is to generate proof-of-principle data on the most promising of the two lead compounds through an in vivo tau mouse models. Aim 3 is to optimize the drug-like PK profile in order to have a Development Candidate suitable for IND-enabling studies.
Impact on Diagnosis/Treatment of Parkinson’s disease: Targeting Tau at the earliest stage of propagation has the potential to alter the disease course of Parkinson’s Disease and significantly impact patients who have early-diagnosis.
Next Steps for Development: Following this project, Psy Therapeutics will advance the program into IND-enabling studies as we drive towards entering Phase I clinical trials. There is also a vast potential for this program to have major upside in other Tauopathies such as Alzheimer’s Disease and FTD.