A New Hope
A team at Lancaster University in the U.K. has discovered that a drug designed to treat type 2 diabetes may hold the key to fighting the memory loss that accompanies Alzheimer’s disease. Their study has been published in Brain Research.
The medication is a triple receptor drug that combines the growth factors GLP-1, GIP, and Glucagon to protect the brain from degeneration. The researchers tested the medication using transgenic mice expressing the mutated genes that cause Alzheimer’s in humans. These genes run in families and are responsible for a form of Alzheimer’s that can be inherited.
The researchers observed the mice as they made their way through a water maze. They discovered that the mice treated with the diabetes compound showed an improved memory and sense of direction. Remarkably, the drug not only seemed to protect the brain, but also to reverse some of the damage caused by the amyloid plaques that progressively kill the neurons of Alzheimer’s patients.
“The way the drug works is that it can help neurons to repair and restore their functions again. It cannot bring back dead neurons — once they are gone, they are gone,” lead author Christian Holscher of Lancaster University told Futurism. “However, there are a lot of stressed neurons that are still alive but no longer function properly. That’s where the window of opportunity lies.”
“The first clinical trials showed the same effect in people, so it is not just some mouse artifact,” added Holscher. “A recent phase II clinical trial in Parkinson’s patients showed some really nice results, so we are getting close!”
Because diabetes is a risk factor in Alzheimer’s, some scientists are hopeful that diabetes drugs could be effective treatments for neurodegeneration. According to the study, the link between the two could be that insulin signaling is impaired in Alzheimer’s patients’ brains. However, that doesn’t mean that all diabetes drugs can help treat brain diseases, too.
“We have tested a number of [diabetes drugs], but not all of them show such protective effects,” said Holscher. “Metformin has been tested in Alzheimer patients but showed nothing.” The drugs that have been shown to work are from the class of “incretin hormone” agonists, which are used to keep glycemic levels under control in diabetic patients.
While the Lancaster University team’s research is promising, it does have some shortcomings.
“The animal data shown here would suggest this could be a potential disease modifying treatment, but these experiments were performed with a peptide that was injected daily, which is not very feasible in clinical settings,” Dean M. Hartley, director of science initiatives with the Alzheimer’s Association, told Futurism. He also noted that animal models have traditionally been poor in predicting human efficacy for Alzheimer’s disease treatments.
Eliezer Masliah, director of the Division of Neuroscience at the National Institute on Aging, expressed cautious optimism at the study’s results.
“Their results are of great interest given the urgent need to develop treatments for Alzheimer’s,” he told Futurism. “However, more detailed studies will be desired to determine the translatability of this work [to the disease]. For example, at which critical window of Alzheimer’s disease will these class of drugs be more effective?”
Answers to Masliah’s questions and others may emerge through further research. Once phase II testing is completed, a potential phase III trial in humans could follow. After that, the new compound could be licensed as a treatment for Alzheimer’s disease. “The timeline will depend on the funding; that is usually the limiting factor,” said Holscher. “It could be as fast as three years, but five years is a more realistic estimate.”
Approximately 44 million people worldwide have Alzheimer’s, but the disease impacts the lives of far more people than that. Family and friends suffer alongside the afflicted, watching as their loved ones slowly lose their cognitive abilities. If the Lancaster University team’s research can help reverse the memory loss caused by Alzheimer’s disease, the impact would be tremendous.