January 2, 2018

expert reaction to study investigating a type 2 diabetes drug for Alzheimer’s symptoms in a mouse model

Publishing in Brain Research, researchers have looked at the role of a drug that is used in treating type 2 diabetes in memory loss in mice.

Dr David Reynolds Chief Scientific Officer, Alzheimer’s Research UK, said:

“Not only has the discovery of a link between diabetes and Alzheimer’s risk empowered people to take positive action around their brain health, it has also presented a promising avenue for research into better treatments.

“Alzheimer’s is a complex disease involving many different brain changes and it is important to come at these from as many different angles as possible. It is great to see encouraging findings emerging from research, and this study broadens efforts towards a treatment that could tackle damage to the brain in the disease.

“Both Alzheimer’s and diabetes involve changes in glucose metabolism and researchers are investigating whether existing diabetes drugs could improve symptoms in people with Alzheimer’s by boosting this process. While this triple agonist drug has been developed to improve glucose metabolism in diabetes, unfortunately this study didn’t measure this effect, making it difficult to understand what the mechanism underlying potential memory improvements might be.

“The researchers didn’t test the drug in mice without features of Alzheimer’s and without this important control group it is difficult to interpret these results with confidence. While the treated-mice showed signs of improvement in their ability to navigate a maze, this picture is not clear and by some measures they did not perform any better in this test than they would have due to chance.

“Animal studies are a vital first step in research but positive signs like these do not always translate into benefits in people. Future studies will need to build on these findings to further assess the potential of this drug and its suitability for testing in people.

“Currently half a million people are living with Alzheimer’s in the UK and with this number on the increase, we urgently need to find treatments capable of stopping the disease in its tracks. There is a long road between studies that show an effect in animals and treatments in the hands of patients, and scientists will only be able to realise the potential of promising findings like these if we continue to invest in research.”

Prof Tara Spires-Jones, UK Dementia Research Institute Programme Lead and Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“Diabetes is associated with an increased risk of Alzheimer’s disease, and this study tested whether a drug designed to treat diabetes could benefit mice that model some aspects of Alzheimer’s pathology.  While the study is promising, there are several technical limitations which urge caution in interpreting the results.  There was not a group of control mice (not the Alzheimer’s model) treated with the drug. The experiments were also only run in a single mouse model which mimics some of the very early brain changes in Alzheimer’s disease. Thus while the results of this study are promising, these are a long way from knowing whether a similar treatment will prevent or reverse dementia symptoms in people.”

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

“The results showing less amyloid deposition of amyloid in mice treated with glucagon receptor stimulating drugs is interesting.  However, it should be noted that several other drugs have shown positive results in mice models of Alzheimer’s disease and then failed in human trials.  While these results are interesting, they are at best, the first step in demonstrating that a drug might work in man.”

Prof Clive Ballard, Professor of Age-Related Diseases, University of Exeter Medical School, said:

“Professor Holscher has previously published strong behavioural, biochemical and neuroimaging studies showing benefits of another diabetes drug liraglutide in similar mouse models,  leading to a clinical trial of liraglutide in people with Alzheimer’s disease which is currently ongoing”

“Although encouraging, further studies are needed to confirm the breadth of benefits, and most importantly whether this triple receptor approach is in fact a significant advance on liraglutide as a potential treatment.”

“Promising –but not a breakthrough yet in my opinion”

Dr Mark Dallas, Lecturer in Cellular and Molecular Neuroscience, University of Reading, said:

“Using a triple receptor agonist, this study highlights the potential of a diabetes drug to suppress some common dementia hallmarks in a mouse model. Whilst this is the start of a long road for this particular compound, one hopes that these preliminary results combined with the additional knowledge gained from other dementia clinical trials into diabetic medicines, will translate into improved outcomes for people living with dementia.”

* ‘Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer’s disease’ by Tai et al. was published in Brain Research  on Monday 1 January 2018. 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/alzheimers/

Declared interests

Prof Tara Spires-Jones: “I am employed by the University of Edinburgh and am a member of the Grant Review Board for Alzheimer’s Research UK.”

Prof John Hardy: “I consult for Eisai and for Ceracuity on Alzheimer therapeutics.”

Prof Clive Ballard: No conflicts of interest.

Dr Mark Dallas: Dr Dallas receives research funding from Alzheimer’s Research UK and Alzheimer’s Association.

None others received.