April 18, 2016

expert reaction to IL-33 protein for dementia in mice

Finding the causes of, and treatments for, Alzheimer’s disease is important to reduce the burden of ageing, and the authors of a paper published in the journal PNAS report the use as a therapy of a particular protein which is involved in inflammation.

Dr Elizabeth Coulthard, Consultant Senior Lecturer in Dementia Neurology, University of Bristol, said:

“New potential targets for Alzheimer’s disease are very interesting. It will be many years before such an intervention could be tested in humans and robust large-scale clinical trials are required before a new drug is given to patients.”

Prof. John Hardy, Professor of Neuroscience, UCL, said:

“This is an interesting study which suggests modulating the immune response to Alzheimer’s pathology may be a valuable treatment avenue for Alzheimer’s disease.  Many workers in the field, including our group, believe this, though the precise way in which we might modulate the immune response is not yet clear.  This study suggests IL-33 may be a relevant immune modulator.  This would be a surprise because this has not been reliably shown to be important in Alzheimer’ disease before.  Like all such work, one would want to see this work confirmed by others in other mouse models of disease before one got too excited and started to think of this as something which might go into humans.”

Dr Simon Ridley, Director of Research, Alzheimer’s Research UK, said:

“The role of the immune system in Alzheimer’s disease and other causes of dementia is a promising area of focus for drug discovery efforts. This early research in mice highlights a way of boosting the immune system to clear a toxic Alzheimer’s protein, but we’ll need to see the results of clinical trials before we’ll know whether this approach could one day help people living with the disease.

“Alzheimer’s Research UK is investing in drug discovery projects in the UK and internationally, taking the most promising ideas from the laboratory and accelerating their progress towards the clinic. As there are no treatments that can halt the damage caused by Alzheimer’s disease, it’s important that many different approaches are tested in the hunt for new, effective medicines.”

Dr Jennifer Pocock, Department of Neuroinflammation, Institute of Neurology, UCL, said:

“This research is interesting but are mouse models relevant to human disease?  I think some attempt at using human cells should have been made here to assess their phenotype following IL-33 exposure.”

Prof. Martin Rossor, NIHR National Director for Dementia Research, University College London Hospitals (UCLH), said:

“This study is important as it provides another route to reducing the amyloid protein that is thought to be damaging in Alzheimer’s disease. However, there have been many early successes in treating mice that have been genetically modified to produce amyloid deposits but unfortunately these have not transferred to success in treating patients.”

Dr James Pickett, Head of Research at Alzheimer’s Society, said:

“We know that inflammation plays a key role in the development of dementia and some genetic studies have suggested a link between this protein and the development of Alzheimer’s disease.

“Here, the researchers have shown that the protein can lead to short-term improvements in memory and reductions in the amount of amyloid in the brains of mice with symptoms similar to Alzheimer’s disease. They suggest that the protein can switch the function of the immune cells in the brain. Instead of causing harmful inflammation, the immune cells seek out and destroy the toxic amyloid plaques caused by Alzheimer’s disease. It’s still early days for this line of research and we will need to see if similar mechanisms occur in people as in mice.

“With an ageing population and no new dementia drugs in over a decade, the need to find treatments that can slow or stop the disease progression is greater than ever. There are already some clinical trials looking at inflammation – this latest finding adds to our understanding of why targeting inflammation may be a promising approach.”

Dr Tara Spires-Jones, Interim Director, Centre for Cognitive and Neural Systems, University of Edinburgh, said:

“This paper is very interesting as it forms part of a growing trend in the field towards merging two previously separate hypotheses about disease pathogenesis. Loss of synapses, the connections between brain cells, is a key feature of Alzheimer’s disease.  Activation of the brain’s immune system is also implicated in causing Alzheimer’s.  Recently, these two key players in the disease process have been found to interact.  This paper continues merging these fields.

“Scientists observed that treating mice that model some aspects of Alzheimer’s with an immune system molecule called Interleukin 33 reverses some of the damage to synapses and the associated memory impairments. While this helps scientists with the puzzle of the molecular mechanisms causing dementia, it is important to keep the results in perspective. These results will need verification before understanding whether a similar treatment will be effective in human patients, but it is a promising avenue of research.”

Prof. Gordon Wilcock, Emeritus Professor of Geratology, University of Oxford and Honorary Consultant Physician, The 2gether NHS Foundation Trust, Cheltenham, said:

“This is additional evidence that the immune system may be implicated in the development of Alzheimer’s disease, and really is important since it suggests a potential therapeutic strategy. Nevertheless, we need further research in people since mouse models are a long way from the human condition.”

‘IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline’ by Fu et al. published in PNAS at 8pm UK time on Monday 18^th April. 

Declared interests

Dr Coulthard: “No conflicts”

Prof. Hardy: “Consulting – Eisai Pharmaceuticals”

Dr Ridley: None received

Dr Pocock: None received

Prof. Rossor: None received

Dr Pickett: None received

Dr Spires-Jones: “I have no conflicts of interest with this paper.”

Prof. Wilcock: “I have no conflict of interests to declare.”