December 8, 2015

expert reaction to molecule that may remove amyloid plaques in mice

A group of scientists has published their work in mice in the journal Nature Communications, reporting the use a molecule capable of separating clumps of proteins which are a feature of Alzheimer’s disease in humans.

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

“There is currently a strong focus on developing treatments for Alzheimer’s that aim to stop the build-up of the hallmark Alzheimer’s protein, amyloid, in the brain. Although some anti-amyloid drugs are currently in late-stage clinical testing, several trials have also failed and there is much debate as whether this is a suitable approach for a new treatment. Many of the current drugs being explored act to stop the formation of amyloid plaques in the brain which mean they may need to be given early in the disease process.

“This interesting study in mice uses a chemical able to break down Alzheimer’s plaques in the brain after they’ve already formed, potentially presenting a way to circumvent the difficult issue of timing with this treatment approach. While this is an appealing prospect, the research is still at the early stage of being explored in animals. Research in animals is an important step in developing any new treatment, but we’ll need to see the findings translated into clinical studies in people before we could know the potential of EPPS to treat Alzheimer’s in humans.

“With no new treatments for Alzheimer’s licensed since 2002, we urgently need to capitalise on promising early science to make sure it’s progressed as quickly as possible towards clinical testing. Alzheimer’s Research UK has launched several large initiatives, including our Drug Discovery Alliance, to ensure that positive early findings can be moved towards new treatments for diseases like Alzheimer’s more quickly.”

Prof. Tom Dening, Professor of Dementia Research, Institute of Mental Health, University of Nottingham, said:

“From a clinician’s point of view, this research is of interest, but we still don’t know if removing amyloid plaques is useful in humans. It may well be that the appearance of plaques is too far down the chain of molecular processes to be beneficial. We don’t know if this animal work will lead to any useful agent that can be used for clinical trials. Therefore it seems like it’s a long way from a breakthrough in the treatment of Alzheimer’s disease. My advice to editors is not to hold the front page.”

Dr Frances Edwards, Reader in Neurophysiology, UCL, said:

“This is an interesting paper presenting a potentially useful preventative therapy for Alzheimer’s disease but, while mouse models are very useful, we have to be very careful about the interpretation of the data in relation to the human condition.

“The clearing of the amyloid is impressive and if it can be repeated in other models it may well reflect what would happen in people with Alzheimer’s disease. However, the memory deficits reported are unlikely to be relevant to the human condition. In humans (and in many mouse models) plaques alone do not cause diagnosable memory loss. Diagnosis comes only when the disease has progressed further with build- up of neurofibrillary tangles and considerable loss of brain tissue.

“If we could catch Alzheimer’s disease before this occurred, such an amyloid-removing drug might stop it in its tracks, but once tau tangles and neurodegeneration have set in this approach would be unlikely to be effective.

“Many more tests need to be done, but for people with the rare inherited forms where Alzheimer’s disease can be predicted long in advance, this could be a very interesting drug indeed.”

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

This is a promising preclinical study in a few dozen mice that found a drug treatment that reduced levels of amyloid beta, one of the pathological proteins found in the brains of Alzheimer’s patients.  While very interesting, this potential treatment is a long way from human patients.   It is important to keep in mind that many treatments have been found that lower amyloid beta and reverse memory symptoms in disease models and very few make it to clinical testing in human patients.

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

“While new insights into potential ways to treat Alzheimer’s disease are welcome, in this case, it’s too early to say if this will one day benefit people living with Alzheimer’s. This study has found a new chemical that could help to clear some forms of amyloid, the toxic protein that is a hallmark of Alzheimer’s disease. However, so far this has only been shown in mice, which do not fully replicate several of the important changes that we see in the brains and behaviours of people with dementia.

“We are working to increase our understanding of Alzheimer’s disease all the time, and there are already a number of drugs in clinical testing that are targeted against amyloid. We hope that new findings will one day translate into real treatments for people living with dementia.”

‘EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-ß oligomers and plaques’ by Kim et al. published in Nature Communications on Tuesday 8^th December. 

Declared interests

None declared