Instead of focusing on fighting the plaques linked to Alzheimer's, researchers took a look at boosting electrical oscillations in the brain. The molecule they invented got the job done in mice, offering hope for a new treatment path for humans.
While it's becoming more and more clear that plaques in the brain are a symptom and not necessarily the cause of Alzheimer's disease, most of the current treatments for the condition work by blasting these plaques away. The FDA-approved drugs lecanemab and aducanumab work this way but, while they might be able to slow the degree of cognitive decline, they can't reverse the cognitive and memory-degrading effects of the disease.
“They leave behind a brain that is maybe plaqueless, but all the pathological alterations in the circuits and the mechanisms in the neurons are not corrected,” says Istvan Mody, a professor of neurology and physiology at UCLA Health.
Seeking an alternative treatment option, Mody and his team turned to gamma oscillations – high-frequency brain waves that have been associated with memory and other cognitive processes. These frequencies are often degraded 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 led to reduced plaques. Once again though, no cognitive improvements were seen.
This time around, the researchers looked to boost gamma oscillations from inside, rather than outside, the brain. They created a molecular compound called DDL-920 that worked to inhibit the action of the chemical messenger known as GABA, which serves to dampen gamma oscillations in fast-firing structures known as parvalbumin neurons. With GABA inhibited, the thinking was that the gamma oscillations would be boosted back to normal levels and memory and cognition would improve.
In mouse tests, that's exactly what happened. When mice that were genetically modified to have Alzheimer's disease were given the compound, their previously poor performance in a maze improved to equal 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 did not notice any visible side effects during the testing phase.
“There is really nothing like this on the market or experimentally that has been shown to do this,” said Mody, who is lead author on the study describing the research that has just been published in the journal PNAS.
Mody says a good deal more research will be required to see if the treatment will be safe and effective in humans, but if it is, he says the discovery offers a brand-new way to treat the disease. He also says DDL-920 could be effective in treating other conditions with hallmarks that include reduced gamma oscillations such as autism spectrum disorder, depression, and schizophrenia.
Source: UCLA Health
