While there was no major breakthrough announced among the drug news saved for the final day of the Alzheimer's Association International Conference 2019, there were a couple of novel approaches — inhaling insulin to banish memory loss, for one — with at least some positive results behind them.
These small if promising clinical trial results helped part, at least a bit, the dark research cloud that had hung over the conference after it was announced on the eve of the major yearly get-together of Alzheimer's disease experts that two clinical trials of Alzheimer's drugs were met with failure.
That news had stirred debate on the viability of finding a cure by targeting amyloid beta in particular, as the failed drugs had been designed to do. While most researchers accept that understanding how and why the neuron-destroying protein builds up in the brain is an important part of the Alzheimer's riddle, some now say that as a drug target, amyloid beta likely appears too far along in the disease progression to make halting it an effective treatment goal.
As Maria Carrillo, chief science officer of the Alzheimer's Association, said in a statement: “Anti-amyloid drugs, though possibly helpful in the earliest stages of Alzheimer's, have not yet proven effective in mild to moderate stages of the disease, even when they clear the brain of amyloid plaques. However, amyloid research, especially in Alzheimer's prevention trials … may still prove fruitful."
Today's clinical trial results, still in the early stages of review, are related to new approaches that have little to do with amyloid beta.
The first, which was described as a small but promising trial, involved giving inhaled insulin to trial participants for 18 months. While there seemed to be critical differences in results depending on the type of device used to deliver the insulin, one group, at least, showed significant benefits in memory and thinking, day-to-day functioning and biological markers for Alzheimer's as seen in cerebrospinal fluid.
The study's leader, Suzanne Craft, professor of gerontology and geriatric medicine at Wake Forest School of Medicine, notes that the improvements seemed to increase over time and that they applied to those who were already showing dementia symptoms. The results presented at the conference, she says, “provide sufficient evidence for a larger study to be conducted.”
The second drug, called COR388, follows on the decades-long research hunch that gum disease could be strongly associated with Alzheimer's. Several studies here and abroad have shown that the same bacterium that causes gum disease can enter the brain through one of two pathways, either crawling up nerves or through the bloodstream.
Once in the brain, this bacterium “chops up proteins in the cells, such as neurons, causing them to collapse and die, triggering the inflammation, neurodegeneration and immune responses that are hallmarks of Alzheimer's. It's like having termites in your brain cells,” says Michael Detke, M.D., chief medical officer of Cortexyme in South San Francisco, California.
His company's drug deactivates the action of the bacterium. It has been shown to be safe and well-tolerated in early trials, Detke says.
But some experts met the news with skepticism, starting with the idea that mouth bacteria hold the key to Alzheimer's treatment. While there is strong evidence that infection or microbes in general play a part in Alzheimer's disease etiology, “exactly what that is and how important that is still not very clear,” says Robert Moir, assistant professor in neurology at Harvard Medical School and Massachusetts General Hospital in Boston.
"While gingivitis bacteria might be a player, it is probably not going to be a major player, and we're not just going to cure Alzheimer's disease by treating it,” Moir says. Microbes, he says, may just accelerate the disease.
Joseph Kass, director of the Alzheimer's Disease & Memory Disorders Center at Baylor College of Medicine in Houston, says he doubts that gum disease is the research equivalent of a smoking gun, and points to the fact that while poorer states like West Virginia have a higher rate of gum disease, they don't have a higher rate of Alzheimer's.
"That one simple thing can cause this very complex disease is a little bit of wishful thinking,” he says. Kass believes there may be multiple triggers for the disease for different people — and that anything from microbes to viruses such as herpes might kick things off.
The third clinical trial news at the conference was presented by researchers at NeuroActiva in Sunnyvale, California, who reported on their drug, called NA-831, which they say may prevent or slow the loss of neurons that occur in Alzheimer's disease as well as stimulate new ones.
"We design drugs that target neurotransmission and reconnect it. We are trying to revitalize the [brain's] communication system and hope to restore memory and improve the quality of functioning,” says Lloyd L. Tran, NeuroActiva's chairman and CEO.
In their early-stage trial, 79 percent of patients with mild to moderate Alzheimer's disease who took the treatment daily for six months showed a significant improvement in their cognition compared with patients given a placebo. “If we give it to patients for a longer time, they may improve even more,” Tran says.
Other experts said they need more information to understand how the exact mechanism of the drug worked. “It's hard to say what it is doing in the brain in relation to improving cognition,” says Rebecca Edelmayer, director of scientific engagement at the Alzheimer's Association.