Instead of focusing on fighting the plaques linked to Alzheimer's, the researchers looked at boosting electrical oscillations in the brain. The molecule they invented worked in mice, offering hope for a new treatment path for humans.
While it’s becoming increasingly clear that plaques in the brain are a symptom of Alzheimer’s disease and not necessarily its cause, most current treatments for the disease work by destroying these plaques. The FDA-approved drugs lecanemab and aducanumab work in this way, but while they can slow the degree of cognitive decline, they can’t reverse the cognitive and memory-impairing effects of the disease.
“Maybe they leave a plaque-free brain, but not all the pathological changes in the circuits and mechanisms in the neurons are corrected,” says Istvan Mody, MD, professor of neurology and physiology at UCLA Health.
Looking for an alternative treatment option, Mody and his team turned to gamma oscillations, high-frequency brain waves associated with memory and other cognitive processes. These frequencies are often disrupted in people with Alzheimer’s, and previous research has shown that stimulating Alzheimer’s patients with auditory, visual, or transcranial signals that mimic gamma oscillations reduces plaques. But once again, no cognitive improvement was seen.
This time, the researchers tried to increase gamma oscillations from inside the brain rather than outside. They created a molecular compound called DDL-920, which works by blocking the action of a chemical messenger known as GABA, which acts to dampen gamma oscillations in fast-firing structures known as parvalbumin neurons. It was thought that by blocking GABA, gamma oscillations would return to normal levels and memory and cognition would improve.
That’s exactly what happened in the mouse tests. When mice genetically modified to have Alzheimer’s disease were given the compound, their previously poor performance on the maze improved to match that of healthy mice. What’s more, it only took two weeks of twice-daily oral dosing for the improvement to be seen. The researchers also didn’t notice any visible side effects during the testing phase.
“There really is nothing like this on the market or experimentally,” said Mody, lead author of the study describing the newly published research in the journal Nature. PNAS.
Mody says much more research needs to be done to see if the treatment will be safe and effective in humans, but if it is, he says the discovery offers a whole new way to treat the disease. He also says DDL-920 could be effective in treating other disorders that have hallmarks like reduced gamma oscillations, such as autism spectrum disorder, depression, and schizophrenia.
Source: UCLA Health