ARUKAlzheimer’s Research UK has appointed three Chief Scientific Officers to drive its £30 million Drug Discovery Alliance, a unique drug discovery venture in dementia research.

Below, we speak to the Chief Scientific Officers of the three Drug Discovery Institutes that make up the Alliance; Dr John Skidmore (University of Cambridge), Dr John Davis (University of Oxford) and Prof Paul Whiting (University College London).

What is the aim of the Alzheimer’s Research UK Drug Discovery Alliance?

JS: The Drug Discovery Alliance will accelerate the discovery of novel, effective therapeutics for Alzheimer’s and other neurodegenerative diseases. We’re looking to couple the deep disease knowledge of academia with our own in-house drug discovery expertise.

Our objective is to explore new biological targets – for each target we will aim to develop lead compounds suitable for proof-of-concept studies in cells, tissue and animal models. Over the next five years we aim to generate six such lead series, each of which will have the potential to deliver an experimental drug. But to do this we need to engage with the research community, to find targets previously unexplored for dementia research which we can then build drug discovery projects around.

What are you looking for in a target?

JD: Targets come in all shapes and sizes and we will aim to be open minded with regard to the rationale behind the target and the proposed approach to tackling the target. Ideally there will be some links to the human disease and some validation data using molecular knockdown techniques. Additional factors that we need to consider, but which are not always at the forefront of a researcher’s mind, are the tractability of the specific molecular target and the possible side-effects of a particular approach.

What degree of validation do you want to see in target proposals?

JS: We’re keen to engage in informal discussions at any stage about disease mechanisms or pathways that researchers are exploring, but we will prioritise targets that have a degree of target validation.

PW: Target validation is often a challenge. There can be a disconnect between the degree of validation carried out in academic labs, and the levels required by the pharmaceutical industry to ‘de-risk’ early-stage drug discovery projects. The beauty of the Drug Discovery Alliance is that we can work with teams with interesting targets, to robustly validate these approaches before embarking on further development within the Drug Discovery Alliance. Some questions we’d be seeking to answer are whether the target should be blocked or activated or are any knockdown studies complemented by small molecule or antibody approaches. One of the earliest challenges for our biology teams will be designing the right assays to probe the novel targets that come on board.

JD: Alongside our call for novel targets implicated in Alzheimer’s and other causes of dementia, the University of Oxford houses a state-of-the-art screening facility, which forms part of the £8 million UK-National Phenotypic Screening Centre. Phenotypic screening is a powerful method for drug discovery because it offers the opportunity to go beyond a focus on single drug targets and broaden the search to pathways involved in disease progression. Together with its counterpart at the University of Dundee, the screening facility represents the most advanced in the UK.

JS: We want to have an open dialogue with the research community. Rather than putting up boundaries to halt the translation of promising targets, we will take a supportive approach, working with scientists to develop their ideas further.

How will the three Drug Discovery Institutes work together?

PW: While we will draw on individual strengths within our host institutions to drive innovation and progress, the three Institutes will keep an open dialogue to maximise potential for developing promising targets.

JS: Targets not incorporated into the portfolio of an individual Drug Discovery Institute could be considered by the other two Institutes and there is a strong culture of collaboration and support across the Alliance.

JD: Many researchers have been asking which Institute they should approach with their ideas. We anticipate that existing collaborations with our host institutions will drive much of the dialogue, but this is not a pre-requisite to partner with the Drug Discovery Alliance. We’re keen to hear from researchers across the dementia research community, not solely those working at Cambridge, Oxford and UCL. Proposals can also be sent to and will be reviewed by all three Chief Scientific Officers.

How will you partner with the pharmaceutical and biotechnology sector?

JD: Pharma and Biotech are important potential partners who we are hoping will continue some of the drug discovery programmes that we initiate. As a result, we are looking for a continuous conversation with Pharma/Biotech to highlight areas of interest, to form collaborations when appropriate to the execution of a project and to help us progress the projects as they become more advanced.