In groundbreaking research, scientists have identified a molecule that may reverse cognitive decline and restore lost memories in Alzheimer’s disease, at least in mouse models. The study, published in the Proceedings of the National Academy of Sciences, was conducted by researchers at the University of California at Los Angeles (UCLA) and represents a novel approach to tackling the debilitating effects of Alzheimer’s.
Unlike existing Alzheimer’s treatments, the new molecule, synthesized at UCLA’s Drug Discovery Lab and named DDL-920, operates through a different mechanism. Traditional Alzheimer’s treatments focus on the accumulation of amyloid plaques in the brain, which is widely believed to be a key driver in the disease’s progression. Over the years, scientists have developed various strategies to eliminate these plaques, but with limited success. Recent studies have revealed that even though monoclonal antibodies can remove these plaques, they fail to restore cognitive abilities or reverse memory loss.
UCLA neurologist and lead researcher Istvan Mody pointed out this limitation. “They leave behind a brain that is maybe plaqueless,” Mody explained, “but all the pathological alterations in the circuits and the mechanisms in the neurons are not corrected.” This statement underscores the need for treatments that go beyond plaque removal and address the underlying neuronal dysfunctions associated with Alzheimer’s.
In addition to plaque buildup, another hallmark of Alzheimer’s, particularly in its early to mid-stages, is the disruption of gamma oscillations in the brain. These oscillations are crucial for functions like memory recall, such as remembering a phone number. The decline in these gamma oscillations is one of the processes that DDL-920 aims to target.
The UCLA research team conducted trials using both “wild-type” mice and mice genetically engineered to develop Alzheimer’s-like symptoms, a method that, while effective for research, has raised ethical concerns among some experts. The researchers hypothesized that DDL-920 could counteract the mechanisms that slow down these vital gamma oscillations.
Following two weeks of oral administration of the drug containing DDL-920, the mice with Alzheimer’s were able to perform on par with the wild-type mice in maze tests designed to measure memory and cognitive function. Remarkably, the treated mice also did not exhibit any abnormal behaviors after receiving the drug, suggesting that DDL-920 may not have adverse effects on behavior, which is an encouraging sign for the molecule’s potential as a treatment.
Despite these promising results, Mody emphasized that there is still a significant amount of research needed to determine whether DDL-920 is safe and effective for use in humans. The transition from mouse models to human clinical trials is a complex and often lengthy process, with many promising treatments failing to make it through. However, if successful, DDL-920 could also have implications for other neurological disorders characterized by disrupted gamma oscillations, including autism spectrum disorder, depression, and schizophrenia.
“We are very enthusiastic about that,” Mody said, reflecting on the broader potential of this research, “because of the novelty and the mechanism of action that has not been tackled in the past.” His optimism highlights the significance of this discovery, which could open new avenues for understanding and treating Alzheimer’s and possibly other neurological conditions.
This study marks an important step forward in the quest to find effective treatments for Alzheimer’s, a disease that affects millions of people worldwide and currently has no cure. While the journey from laboratory research to a marketable treatment is fraught with challenges, the discovery of DDL-920 offers a glimmer of hope for those affected by this devastating condition.
