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One step at a time against Alzheimer’s
August 2015
by Lloyd Dunlap  |  Email the author
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LONDON—Funding worth nearly half a million pounds (about $780,000) will unite academics at the University of Southampton with drug discovery experts at the medical research charity MRC Technology to target the immune system in the hunt for new treatments for Alzheimer’s disease.
 
The work is the first to be funded by the Dementia Consortium, a discovery collaboration between Alzheimer’s Research UK, MRC Technology and the pharmaceutical companies Eisai and Eli Lilly. By uniting expertise, this focused cash injection is intended to be an initial step in bridging the gap between academic research and the pharmaceutical industry in the search for new drugs to slow the development of Alzheimer’s.
 
According to Steve Suchting, business development manager at MRC Technology, the consortium was the result of the fact that no new development to treat brain inflammation, including Alzheimer’s, had been introduced in many years, and new models for drug discovery were required. MRC will bring its drug discovery resources to bear and provide project management.
 
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.”
 
Suchting notes that the consortium is in the “pre-competitive” stage and that new partners may be added. Ultimately as much as £3 million in funding may be made available.
 
“The project is milestone-driven,” he states, “and all partners participate in meetings. The endpoint of the project is to prove that the target can be modulated.”
 
On the academic side, 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 Alzheimer’s 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.
 
According to Gomez-Nicola, “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, specialized 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.”
 
CSF1R is a key player in regulating the brain’s immune response. In their previous studies in mice, the University of Southampton 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 crossing the blood-brain barrier.
 
This investment via the Dementia Consortium will allow the researchers to explore other, more targeted approaches to block CSF1R—important groundwork before any new treatment can go into the clinic.
 
“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,” Gomez-Nicola states.
 
Dr. Eric Karran, director of research at Alzheimer’s Research UK, adds, “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.”
 
“Neuroinflammation is emerging as a key contributing factor in driving Alzheimer’s disease pathology,” notes Dr. Andy Takle, Eisai’s senior director of Open Innovation, UK. “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 recognize 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 for neurodegeneration at Eli Lilly, echoed those sentiments by saying, “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.”
 
Code: E081504

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