Last month, charity Alzheimer’s Research UK launched a new initiative in the hunt for a dementia treatment – the Drug Discovery Alliance. Here Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, discusses the Alliance and the role of academic institutions in the search for a dementia treatment.
Academia and industry can no longer be viewed as entirely separate entities. As pharmaceutical companies move away from in-house target discovery in favour of a broader research base, academia is playing a larger role in the drug discovery process. With the failure rate for Alzheimer’s drug trials over the last decade approaching 100% (Cummings, J. et al 2014), we require focused investment in robust target validation and early stage drug discovery to ensure another decade doesn’t pass without a new treatment for Alzheimer’s or other causes of dementia.
Alzheimer’s Research UK has recently launched a £30 million Drug Discovery Alliance – a network of Drug Discovery Institutes based at the University of Cambridge, University of Oxford and University College London. This is a unique initiative in the UK dementia research community, and one of only a handful of such enterprises in the world. The aim is to channel innovative science towards new medicines as quickly as possible.
‘Disease-modifying treatment by 2025’
The World Innovation Summit for Health (WISH) Dementia Forum 2015 report highlights the global burden of dementia. As well as continuing to search for symptomatic treatments, there is a need to focus on developing treatments that attack the diseases at the root of dementia. At the G8 Dementia Summit in London 2013, world health leaders pledged to find a ‘disease-modifying treatment for dementia by 2025’. Over the past three years the Prime Minister’s Challenge has played a pivotal role in creating a heightened focus on dementia and boosting the case for more research. Such a therapy, which could delay the onset of dementia by 5 years, could reduce the number of people living with dementia in the UK by 36% by 2030 if introduced in 2020; the impact on informal carers would be similarly striking (Lewis, F et al 2014).
However, it seems the traditional model of pharmaceutical-driven drug discovery won’t meet this target. The WISH report highlights the retreat of the pharmaceutical industry from neuroscience research. Between 2009 and 2014, CNS programmes at 11 large pharmaceutical companies, halved (Choi, D et al 2014). This withdrawal has been attributed to the high risk of investment in neurodegenerative research; the neuroscience research pipeline is particularly expensive and hard to fill, clinical trials are longer than average compared to other therapeutic areas and regulatory agency review times are lengthy – 35% longer than for non-CNS drugs (Choi, D et al 2014).
For the best chance of success in developing a new Alzheimer’s drug, parallel approaches are required (Lo, A et al 2014). The broad research base in academia fosters ‘disruptive innovation’, allowing new insights, technologies and model systems to be developed from unexpected sources. We need to harness these innovative ideas and turn them into targets for new treatments. The field of academic drug discovery is growing, with academic research funding behind 18% of drugs recently approved by the European Medicines Agency. We’re starting to see tangible successes in the field of oncology; the first effective treatment for advanced prostate cancer, Abiraterone, was developed at the publically funded Institute of Cancer Research, London and three more therapeutic agents are on the market due to work at Cancer Research UK-funded drug discovery units.
It is clear that a coordinated drug discovery effort housed in an academic institution can provide fully optimised leads to take through to the clinic. People frequently draw parallels between cancer and dementia, the latter facing the stigma that has almost been erased for cancer over the last 25 years. Survival rates for cancer have doubled in recent years, a testament to the investment, infrastructure and drug discovery work that’s been focused on this disease. We are learning lessons from this success and know that with the right strategy and investment, we can make the same strides in dementia. The three Alzheimer’s Research UK Drug Discovery Institutes will build on the approach and success of similar initiatives in other therapeutic areas, and augment the current drug pipeline for Alzheimer’s and other causes of dementia.
Open dialogue will be crucial for the success of the Drug Discovery Alliance as we know that we must take several approaches, involving a raft of varying expertise. The Drug Discovery Institutes will act in parallel to the Dementia Consortium, a partnership between Alzheimer’s Research UK, Eisai, Lilly and MRC Technology. Robust target validation and early-phase drug discovery in the academic setting, with expertise from the pharmaceutical industry who will take on promising leads, will serve to accelerate the “bench to bedside” transition.
Dementia is a global crisis. Failures have outweighed success in the route to treatments across all disease areas, but especially in neurodegeneration. Despite concerns about the withdrawal of the pharmaceutical industry, there is optimism for the future. We must learn from previous failures and galvanise the global focus on dementia to stimulate investment in translational dementia research. The Alzheimer’s Research UK Drug Discovery Alliance represents a step-change in the UK dementia community – one which will serve a significant role in supplying the global drug discovery pipeline and ultimately a disease-modifying treatment for people living with dementia.