Diabetes Drug ‘Significantly Reverses Memory Loss’ in mice with Alzheimer’s

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TA-treatment enhanced neurogenesis and increased numbers of DCX positive cell…

TA-treatment enhanced neurogenesis and increased numbers of DCX positive cell numbers in the dentate gyrus of APP/PS1 mice. A: control group; B: APP/PS1 group; C: APP/PS1+TA group. Scale bar in image A: 100 μm. *** = P < .001 compared with the control group; ### = P < .001 compared with the APP/PS1 group. One-way ANOVA with Bonferroni repeated measures post hoc tests. N = 6 per group.

A drug developed for diabetes could be used to treat Alzheimer’s after scientists found it “significantly reversed memory loss” in mice through a triple action. The research, published in Brain Research, could bring substantial improvements in the treatment of Alzheimer’s disease through the use of a drug originally created to treat type 2 diabetes. Professor Christian Holscher of Lancaster University in the UK said the novel treatment “holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer’s disease.”

Alzheimer’s disease is the most common cause of dementia and the numbers are expected to rise to two million people in the UK by 2051 according to Alzheimer’s Society, who part- funded the research. Although the benefits of these ‘triple agonist’ drugs have so far only been found in mice, other studies with existing diabetes drugs such as liraglutide have shown real promise for people with Alzheimer’s, so further development of this work is crucial.” This is the first time that a triple receptor drug has been used which acts in multiple ways to protect the brain from degeneration. It combines GLP-1, GIP and Glucagon which are all growth factors. Problems with growth factor signalling have been shown to be impaired in the brains of Alzheimer’s patients.

The study used APP/PS1 transgenic mice that express human mutated genes that cause Alzheimer’s. Those genes have been found in people who have a form of Alzheimer’s that can be inherited. Aged transgenic mice in the advanced stages of neurodegeneration were treated. In a maze test, learning and memory formation were much improved by the drug which also:-
~enhanced levels of a brain growth factor which protects nerve cell functioning
~reduced the amount of amyloid plaques
~less both chronic inflammation and oxidative stress
~slowed down the rate of nerve cell loss
Professor Holscher said: “These very promising outcomes demonstrate the efficacy of these novel multiple receptor drugs that originally were developed to treat type 2 diabetes but have shown consistent neuro- protective effects in several studies.”

“Clinical studies with an older version of this drug type already showed very promising results in people with Alzheimer’s disease or with mood disorders”
“Here we show that a novel triple receptor drug shows promise as a potential treatment for Alzheimer’s but further dose-response tests and direct comparisons with other drugs have to be conducted in order to evaluate if this new drugs is superior to previous ones.”

Type 2 diabetes is a risk factor for Alzheimer’s and has been implicated in the progression of the disease. Impaired insulin has been linked to cerebral degenerative processes in type 2 diabetes and Alzheimer’s disease. Insulin desensitisation has also been observed in the Alzheimer’s disease brain. The desensitisation could play a role in the development of neurodegenerative disorders as insulin is a growth factor with neuroprotective properties.

http://www.sciencedirect.com/science/article/pii/S0006899317304596?via%3Dihub

https://www.eurekalert.org/pub_releases/2017-12/lu-dd122017.php