Dr Diego Gomez-Nicola and colleagues at the University of Southampton will build on their current finding that a protein in the immune system called CSF1R could be the key to an effective new drug for the disease. Together with drug discovery experts at MRC Technology, they will seek to develop novel therapeutics to target the immune system - a double edged sword in the brain's response to nerve cell death. Researchers now believe that Alzheimer's disturbs the brain's inflammatory response, causing the damage associated with the disease.
CSF1R is a key player in regulating the brain's immune response. In their previous studies in mice, the team found that blocking CSF1R can dampen the inflammatory response to nerve cell death and improve symptoms in other neurodegenerative diseases. However, the compounds currently available to block CSF1R are not ideal to take into the clinic, due to unwanted effects and difficulties getting into the brain. This investment will allow the researchers to explore other, more targeted approaches to block CSF1R - important groundwork before any new treatment can go into testing in people.
Dr Gomez Nicola, Career Track Lecturer and MRC NIRG fellow at the University of Southampton, said: "Inflammation is the body’s response to damage and something we've all experienced but sometimes these mechanisms to defend the body go awry. In Alzheimer's disease, specialised immune cells called microglia are a little too eager to clear damage. Their ranks swell and activity increases, with damaging consequences for surrounding nerve cells.
"This project will allow us to find the best way to interfere with the biological cascade that leads to an increase in microglia numbers. We know that targeting CSF1R is being explored as a potential treatment for cancer and inflammatory conditions, and we hope that by fine-tuning compounds to act specifically in the brain, this approach could be tested for benefits in Alzheimer's too. This crucial drug discovery work in cells and mice should act as stepping stone to develop new treatments that can halt damaging brain inflammation and nerve cell death."
Dr Eric Karran, Director of Research at Alzheimer's Research UK, said: "It's been fascinating to see the academic community dissect the role of inflammation in Alzheimer's disease and learn more about the 'friendly fire' that takes place during the course of the disease. But now we need to translate this interesting biology into tangible benefits for the 500,000 people in this country living with Alzheimer's. It's a long road from research in the laboratory to treatments in the clinic, but investment to boost the number of new drug targets is critical if we are to face this huge medical challenge."
Dr Justin Bryans, Director of Drug Discovery at MRC Technology added: "Our Centre for Therapeutics Discovery has proven capability in drug discovery and as a charity we are ideally placed between academia and pharma to translate promising science into effective treatments for patients."
Dr Andy Takle, Senior Director, Open Innovation, UK, Eisai Ltd., said: "Neuroinflammation is emerging as a key contributing factor in driving Alzheimer's disease pathology. The biological mechanisms that underpin this process are incredibly complex and our understanding relies heavily on information originating from the academic community. For this reason we recognise that collaboration is key in identifying new opportunities to intervene. As a Dementia Consortium partner on this exciting project we look forward to bridging academic expertise with a focused drug discovery effort to develop new medicines for this devastating disease."
Michael Hutton, Chief Scientific Officer, Neurodegeneration, Eli Lilly and Company, said: "Lilly is delighted to support this exciting program as part of the Dementia Consortium, which offers a new model for public-private partnership to support drug development in Alzheimer's disease."
The Dementia Consortium is open to global research teams with innovative targets that need accelerating through the drug discovery process. For further information, please visit http://www.dementiaconsortium.org.
About Alzheimer's Research UK
About the University of Southampton
Through world-leading research and enterprise activities, the University of Southampton connects with businesses to create real-world solutions to global issues. Through its educational offering, it works with partners around the world to offer relevant, flexible education, which trains students for jobs not even thought of. This connectivity is what sets Southampton apart from the rest; we make connections and change the world.
About MRC Technology
MRC Technology is an independent life science medical research charity, offering professional services to organisations within the academic, charity, biotechnology and pharmaceutical sectors globally. Services include IP management and research and development for diagnostics, small molecules and therapeutic antibodies. MRC Technology bridges the gap between basic medical research and commercialisation, helping early discoveries progress to clinical application. Four of MRC Technology's projects have led to approved drugs (Tysabri®, Actemra®, Entyvio®, Keytruda®) and the company has a strong pipeline in development.
Please note MRC Technology has been independent from the UK's Medical Research Council (MRC) since 2000.