The Alzheimer’s field is littered with drug-development failures, but that isn’t deterring a group of British scientists from looking for hope in an unlikely source: diabetes treatments. The team, from Lancaster University, is reporting that an experimental three-part drug originally developed for use in Type 2 diabetes seems to reverse memory loss in mice.
The treatment combines the growth factors GLP-1, GIP and glucagon. The reasoning behind the approach is that growth factor signaling is impaired in the brains of people who suffer from Alzheimer’s, according to a statement from the university.
When administered in mouse models of Alzheimer’s, the treatment reversed memory loss, which was measured via a maze test, the scientists reported in the journal Brain Research. The drug improved learning and memory formation, slowed down the rate at which nerve cells were lost in the brain, and enhanced levels of a growth factor that preserves the functioning of nerve cells, they said. It also reduced the amount of amyloid plaque—the abnormal brain growths that have been implicated in the disease.
This is not the first time diabetes treatments have been tried in Alzheimer’s disease. Novo Nordisk’s Victoza (liraglutide), a GLP-1 agonist, has undergone small clinical trials in people with Alzheimer’s. The results “have shown real promise,” said Doug Brown, Ph.D., director of research and development at the London-based Alzheimer's Society, in the statement.
That said, the most heavily cited clinical trial of Victoza in Alzheimer’s only showed a reduction in the buildup of amyloid plaque. But there was no difference in cognitive ability between trial participants who received the drug and those who took a placebo. That likely explains why further investigation of GLP-boosting drugs in Alzheimer’s has ground to a halt.
Other drugs targeting amyloid plaque have failed in recent years. They include Eli Lilly’s solanezumab and Pfizer's bapineuzumab. The amyloid hypothesis is far from dead, though. Several companies are investigating drugs designed to prevent the buildup of amyloid plaques by inhibiting a protein called BACE, including Biogen, Amgen and Novartis.
So-called triple-agonist diabetes drugs have not yet been tried in people, according to the Lancaster statement, and more work needs to be done before the compound is ready for clinical trials. Lead researcher Christian Holscher, Ph.D., a professor at Lancaster University, says his team will need to do more dose-response testing and test the drug against others that have been tried in Alzheimer’s to determine if it makes sense to move forward.