The drug effects of (Val8)GLP-1 are manifold. Neurons are protected from oxidative stress, and synapses are protected from being attacked by amyloid. Synapses remain functional and memory and cognition is preserved. Professor Christian Hölscher
Scientists from the University of Ulster have been testing the hypothesis that certain drugs intended for the treatment of Type II diabetes could be useful for counteracting the symptoms of Alzheimer’s disease and potentially other neurodegenerative disorders.
The study forms part of ongoing work funded by Alzheimer’s Research UK
, and appeared last week in the journal Brain Research
. Simulating the activity of a protein named GLP-1, which plays a part in controlling the body’s response to changing blood sugar levels, the experimental drug is known as (Val8)GLP-1.
Professor Christian Hölscher, from the Biomedical Sciences Research Institute
(BMSRI) at the University of Ulster’s Coleraine campus, answered some questions from ScienceOmega.com about the research he and his team have been carrying out on the effects of (Val8)GLP-1. I began by asking Professor Hölscher how much is currently known about the link between Type II diabetes and Alzheimer’s disease.
"There is a lot of evidence from epidemiological studies that diabetes is a risk factor for developing Alzheimer's disease (AD)," he said. "It has also been shown that insulin signalling in the brains of Alzheimer patients is impaired. That has serious repercussions, since insulin is a growth factor. Without this signal, cells do not function so well and do not divide as often."
(Val8)GLP-1 was originally designed to tackle Type II diabetes, but the effects that it has been observed to have on the brain suggested that it may be useful in treating certain neurodegenerative diseases too.
"(Val8)GLP-1 enhances insulin release during episodes of high blood sugar levels," explained Professor Hölscher. "The drug acts as a growth factor and can protect neurons, and also re-sensitises insulin signalling in diabetes and in the brain of AD patients. It is not currently used to treat diabetic patients because the two drugs on the market are considered superior in their ability to control Type II diabetes."
In tests on healthy mice, (Val8)GLP-1 was able to cross the blood-brain barrier and did not appear to have any adverse side effects. The study from the BMSRI indicates that, as well as protecting existing brain cells, the drug could also promote the growth and replacement of neurons – a very exciting prospect for the future of Alzheimer’s research.
"The drug effects of (Val8)GLP-1 are manifold," Professor Hölscher stated. "Neurons are protected from oxidative stress, and synapses are protected from being attacked by amyloid. Synapses remain functional and memory and cognition is preserved.
"The drug also reduces the chronic inflammation response in AD and Parkinson mouse models, which is an important factor in both diseases. The inflammation response will affect neurons in the long run, for example by increasing oxidative stress."
The paper also describes the way in which the drug normalises stem cell proliferation in the brain, with the result that neurons can be replaced. This mechanism is impaired in both Alzheimer's and Parkinson's disease, where neurons are not replaced.
It was found that blocking the effect of GLP-1 in the brains of mice resulted in them performing poorly in tasks involving learning and memory. It also seems that the drug can actively improve learning and memory in mouse models of Alzheimer's disease, but those results will appear in a separate paper which has yet to be published.
As far as bringing such drugs to market is concerned, Professor Hölscher is optimistic that the findings of the recently-published research will encourage further testing and development in spite of high costs.
"We are currently running a clinical trial testing liraglutide (Victoza) in patients with Alzheimer's disease," he explained. "We also want to test (Val8)GLP-1 and are hoping to get funding for those trials. They are very expensive, and the research councils have been reluctant to fund this work. However, with the recent success of (Val8)GLP-1 and related drugs, I hope that the funding will now be provided."