A systematic programme to develop and evaluate the best candidate treatments for repositioning as therapies for Alzheimer’s Disease (SMART-AD)

This innovative programme will identify drug candidates for repositioning in Alzheimer’s Disease (AD). Professor Clive Ballard and colleagues at King's College London, will compare the transcriptional signature of AD with the signatures of up to 4000 drugs with established safety in man to identify 100 candidates with the most promising therapeutic potential. State of the art gene profiling will be used to determine the ability of the candidates to modify the expression of disease-associated transcripts in hippocampal neurons, with the best 20 drugs going forward to test for biological efficacy in in-vitro assays for a wide-range of pathogenic mechanisms implicated in AD. The six agents with the most favourable impact will then be evaluated in the best rodent model of AD to obtain the proof-of-principle evidence that would support a clinical program. Importantly assays used will measure a range of key pathological and behavioural outcomes, as well as determining the drugs impact on disease-associated transcriptional changes. Each stage will be overseen by an independent expert panel to ensure drug selection is rigorous and appropriate for AD. The overall aim of this programme of research is to identify the best candidate to be taken forward to clinical trial in people with AD.