A ‘triple receptor’ drug originally created to treat type 2 diabetes could be used to treat Alzheimer’s disease after researchers from China and the United Kingdom found it ‘significantly reversed memory loss’ in mice. The research appears in the journal Brain Research.
Alzheimer’s disease is a progressive neurodegenerative disease, characterized clinically by progressive memory loss, cognitive decline, and aberrant behavior. In Alzheimer’s, changes in tau protein lead to the disintegration of microtubules in brain cells. Image credit: Alzheimer’s Disease Education and Referral Center / National Institute on Aging.
“The novel treatment holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer’s disease,” said co-author Professor Christian Holscher, from Lancaster University.
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 glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, which are all growth factors.
“With no new treatments in nearly 15 years, we need to find new ways of tackling Alzheimer’s,” added Dr. Doug Brown, Director of Research and Development at Alzheimer’s Society, who was not involved in the study.
“It’s imperative that we explore whether drugs developed to treat other conditions can benefit people with Alzheimer’s and other forms of dementia. This approach to research could make it much quicker to get promising new drugs to the people who need them.”
“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.”
Professor Holscher and his colleagues from Shanxi Medical University and Shaoyang University used APP/PS1 mice, which are transgenic mice that express human mutated genes that cause Alzheimer’s.
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:
(i) enhanced levels of a brain growth factor which protects nerve cell functioning;
(ii) reduced the amount of amyloid plaques in the brain linked with Alzheimer’s;
(iii) reduced both chronic inflammation and oxidative stress;
(iv) slowed down the rate of nerve cell loss.
“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 neuroprotective effects in several studies,” Professor Holscher said.
“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.”
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Jingjing Tai et al. 2018. Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer’s disease. Brain Research 1678: 64-74; doi: 10.1016/j.brainres.2017.10.012
