Dr Iain Chessell outlines why AstraZeneca’s ongoing commitment to neuroscience research is so important and explains how we are set up to go the distance in unravelling the riddle of Alzheimer’s disease.
The theme for this year’s World Alzheimer’s Month is Remember Me: Early diagnosis means I can live well for longer. The emphasis on diagnosis is a stark reminder that despite continuing efforts, there are no disease modifying therapies available to treat the 44 million people who are affected by Alzheimer’s or related dementia .1 With these numbers set to rise to over 130 million by 2050,2 the need for new scientific breakthroughs has never been so great.
The challenge of neuroscience
The brain is the most complex object known to us, so it should come as no surprise that neuroscience research is a notoriously challenging field. After decades of effort, we still have a relatively narrow understanding of the biology of neurological diseases compared to other complicated conditions like cancer.
“Neuroscience is very broad,” Iain explained. “What we know of the molecular mechanisms of neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), Parkinson’s and Alzheimer’s disease has only evolved in the last five to 10 years.”
Discovering medicines to treat Alzheimer’s disease has been especially challenging as the brain is relatively inaccessible and harder to test and deliver compounds to.
In the case of Alzheimer’s, the disease is characterised by large clusters of protein found inside and outside the nerve cells of the brain.3 The clusters on the outside of the cells, called plaques, are made of a protein called amyloid-beta. The clusters formed inside cells are neurofibrillary tangles and are formed by a protein called tau.3
“Whilst amyloid-beta and tau are both fundamental hallmarks of Alzheimer’s disease, it’s only recently that the role of the spread of tau has become clearer and a topical area of research,” commented Iain.
Another reason is the sheer scale and diversity of the patient population. There is a broad time scale in which symptoms can appear; with the disease developing anywhere between 10-20 years after amyloid-beta deposits begin.4
The fact that Alzheimer’s disease progresses slowly poses yet another challenge — studies take a very long time and whilst research has led to an improved basic understanding there has never been a therapy which modifies the underlying mechanisms of disease. “There is much more to learn,” Iain said.
Setting up for success
Our Neuroscience team has a unique structure to address the challenges of R&D in neuroscience.
“We are a small, nimble and enthusiastic biotech-like organisation of 27 people. This allows us to chase the new science wherever it happens in the world,” Iain explained. “It also means that everything in our neuroscience portfolio of large and small molecules is the cream of the crop with the highest priority and the most compelling science.”
“It’s also a team that is very experienced in neuroscience, with wide networks and an outward focus meaning that we thrive on learning about new science and building collaborative alliances with organisations who share our passion to advance research.” Chessell continued.
This is distinctive from previous models, which sought to develop all clinical candidates internally, which inevitably came up against the challenge of shouldering large and expensive clinical trials. In contrast, the current model is all about early, flexible partnering, with the brightest and best in the world, which allows AstraZeneca to share the high risks and high costs of neuroscience research.
Looking to the future
After many challenging years in neuroscience, scientific understanding and expectations are gathering pace.
“We chose to commit to neuroscience to address the vast unmet patient need for innovative medicines and we’re making good progress” says Iain.
It is hoped that future World Alzheimer’s Days will welcome the first new treatments to alter the course of the disease and improve the lives of millions of patients around the world.
1 Alzheimers.net. Alzheimer’s Statistics. Available from: http://www.alzheimers.net/resources/alzheimers-statistics/ [Last accessed September 2017]
2 WAM 2017 Corporate Toolkit. Available from: https://www.alz.co.uk/sites/default/files/pdfs/wam-corporate-toolkit-2017.pdf. [Last accessed September 2017]
3 Murphy MP, Levine H. Alzheimer’s disease and the amyloid-beta peptide. J Alzheimers Dis. 2010;19:311–23.
4 Beason-Held LL, Goh JO, An Y et al. Changes in brain function occur years before the onset of cognitive impairment. J Neurosci 2013; 33: 18008–14.
5 Cummings J et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimer's research & therapy 8.1 (2016): 39.