January 18, 2016

expert reaction to cancer drug in Alzheimer’s mouse model memory trial

Publishing in the journal Nature Medicine a group of scientists has used a cancer drug to treat a model of Alzheimer’s disease in mice, and report that the therapy produced an immune response which cleared markers of the disease and improved cognitive performance in the mice.

Dr Tara Spires-Jones, Reader and Chancellor’s Fellow, Centre for Cognitive and Neural Systems, University of Edinburgh, said:

“This new research is interesting because it helps us understand the role of the immune system in Alzheimer’s disease. The brain’s immune system becomes over-activated in Alzheimer’s disease, and there is a debate surrounding whether this activation is harmful, protective, or a bit of both. Many scientists believe that calming down the overactive brain system will be a useful treatment for the disease. However, drugs aimed at doing this, called anti-inflammatories, have not had much success in clinical trials.  This current research builds on the idea that boosting brain immunity will encourage the immune system’s natural potential to clear toxic substances.  Indeed, when the scientists blocked a pathway involved in lowering immune system activity with a drug normally used to treat cancer, they observed improvements in a mouse model of Alzheimer’s disease. While this is scientifically very interesting, it is a long way from being a treatment for human Alzheimer’s disease as this study was in a relatively small number of mice and mice are not a perfect model of human disease.”

Dr Doug Brown, Director of Research and Development at Alzheimer’s Society said:

“It’s clear that inflammation and the immune system play a highly important role in the development of Alzheimer’s disease, but just how that relationship works is incredibly complex and not fully understood.

“It’s early days yet, but this study in mice gives us an indication that activating certain immune cells could be a potential way to clear the toxic build-ups of amyloid, one of the hallmarks of Alzheimer’s disease. However, previous treatments targeting the immune system that have shown promise in mice have failed to have the same effect in people. We’re still a few years away from knowing whether this will hold promise for people with dementia.

“Repurposing drugs that already work for other conditions could provide us with a shortcut to new dementia treatments, and is a key aspect of our Drug Discovery programme.”

Dr Simon Ridley, Director of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:

“This study in mice suggests that PD-1 blockers may warrant further investigation, but further work in the lab is still needed to take this early-stage research forward. The study looked at the effects of the drug at an advanced stage of amyloid build-up, however it is not yet known whether removing amyloid at this late stage will be helpful for memory and thinking in people. Ultimately, clinical trials in people will be crucial to determine whether PD-1 blockers can help fight Alzheimer’s. It will also be vital to understand what impact these drugs might have in the long term.

“With over half a million people living with Alzheimer’s in the UK today and no treatments yet capable of slowing the disease, investment in drug discovery has never been more urgent. For the best chance of success we need to see as many approaches as possible being tested, which is why Alzheimer’s Research UK is investing in a number of initiatives such as our Drug Discovery Alliance to help speed up this type of research.”

‘PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer’s disease’ by Baruch et al. published in Nature Medicine on Monday 18^th January. 

Declared interests

None declared