Abstract

"To reduce the attrition rate early in clinical development and maintain future investment, a consensus regarding the predictive value of behavioural, neuroimaging, electrophysiological, cerebral spinal fluid (CSF) and blood markers is urgently required. The PharmaCog consortium is a unique opportunity for the pharmaceutical industry and academia to combine their collective knowledge, expertise and data in a pre-competitive partnership to deliver a unique translatable platform for drug development in AD. The working hypothesis of PHARMA-COG is that no single physiological, functional or biochemical marker will be sensitive enough to fulfill all or even any of the objectives outlined above, but that a collection of markers will be necessary. To achieve this, a multidimensional “MATRIX” approach is being implemented throughout the project, by conducting parallel pharmacodynamic studies in animals, healthy volunteers and selected patient cohorts, using the same fully translational pharmacodynamic endpoints, the same provocation challenges and therapeutic interventions using single dose and medium-term treatment. This approach is based on i) multi-modal data collection from harmonized animal and human models, ii) extraction of selected features from this data collection (biomarkers/animals, healthy volunteer models, physiological and pharmacological challenges), and iii) advanced quantitative pharmacological assessment of the data generated across modalities and studies.  The pre-clinical and clinical data sets will help define novel models and understanding of disease progression enabling the faster development of new chemical entities for the treatment of Alzheimer’s disease.