A triple receptor agonist developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple mode of action.
Lead researcher Christian Holscher of Lancaster University (UK) said the drug originally created to treat type 2 diabetes "holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer's disease."
Type 2 diabetes mellitus (T2DM) is a well-established risk factor for Alzheimer’s disease (AD). Preclinically, it has been shown that the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have anti-diabetic properties. A triple receptor agonist (TA), which activates GIP-1, GIP and glucagon receptors at the same time was injected once daily (10 nmol/kg i.p.) for 60 days to APP/PS1 transgenic mice suffering from Alzheimer’s. The drug was originally invented by German researchers (account required) to treat type II diabetes.
The results published in Brain Research suggest that the treatment significantly reversed the memory deficit in the APP/PS1 mice, as measured through a spatial water maze test. Moreover, the drug reduced levels of the mitochondrial pro-apoptotic signaling molecule BAX, increased the anti-apoptotic signaling molecule Bcl-2 and enhanced the levels of BDNF, a key growth factor that protects synaptic function. Levels of synaptophysin were enhanced, demonstrating protection from synaptic loss that is observed in AD. Neurogenesis in the dentate gyrus was furthermore enhanced as shown in the increase of doublecortin positive cells. Furthermore, the treatment reduced the total amount of beta-amyloid, reduced neuroinflammation (activated microglia and astrocytes), and oxidative stress in the cortex and hippocampus. The authors conclude that treatment with the drug may be a promising lead for the design of future treatment strategies in AD.
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. "With no new treatments in nearly 15 years, we need to find new ways of tackling Alzheimer's,“ said Dr Doug Brown, R&D Director at Alzheimer's Society. " 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."
According to Holscher, "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." However, further dose-response tests and direct comparisons with other drugs have to be conducted in order to evaluate if the new drug is superior to previous ones.