Stacking the Odds in Alzheimer's Disease Drug Development

September 20, 2016

SysQuant® Case Study #WorldAlzheimersDay

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.


Pathway Enrichment Analysis- SysQuant

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


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