Proteome Sciences : Stacking the odds in Alzheimer's Disease Drug Development #WorldAlzheimersDay

Case Study - Stacking the odds in Alzheimer's disease drug development

We have been developing several drugs that modulate the phosphorylation of the aggregating protein tau in Alzheimer's disease by inhibiting the protein casein kinase 1 delta. We have tested them in a model of human tauopathy (aggregating tau diseases) and analyzed brain tissue with SysQuant to determine the drug's mechanism of action.

SysQuant confirmed that many phosphorylation sites on tau are reduced by drug treatment, including sites that are prevalent in Alzheimer's disease. By taking a comprehensive approach we could also show that many pathways affected by increasing tau pathology in human disease were inversely affected following CK1d inhibition (see Figure 2). As a result of this study we have also identified a number of protein changes that could be followed in peripheral fluids such as cerebrospinal fluid and plasma to confirm and monitor treatment effects in clinical trials.

Figure 2 - Pathway enrichment analysis of quantitative changes in protein expression and activity following CK1d inhibitor treatment in a mouse model of tauopathy