Researchers at UCLA Health have discovered a molecule that shows promise in restoring memory and cognitive function in mice with Alzheimer’s-like symptoms.
This breakthrough could pave the way for a new approach to treating Alzheimer’s disease in humans if further studies prove successful.
The molecule, known as DDL-920, was developed and tested by a team of scientists led by Dr. Istvan Mody and Dr. Varghese John at UCLA. Unlike current Alzheimer’s treatments, which focus on removing harmful plaque buildup in the brain, this molecule aims to “reboot” the brain’s memory circuits.
The researchers are excited about the potential of DDL-920 because it works in a completely different way from existing treatments.
The buildup of plaques in the brain, a hallmark of Alzheimer’s disease, is the target of several recently approved drugs like lecanemab and aducanumab.
These medications help clear plaques and slow down cognitive decline, but they do not restore memory or fix the damaged brain circuits.
“They leave behind a brain that may be free of plaques, but the underlying problems in the brain’s circuitry and neurons remain,” explained Dr. Mody, a professor of neurology and physiology at UCLA.
In the new study, Mody and John, who is the director of the Drug Discovery Laboratory at UCLA’s Mary S. Easton Center for Alzheimer’s Disease Research, decided to take a different approach.
Instead of focusing on removing plaques, they wanted to find a way to reactivate the brain’s memory functions.
The brain uses electrical signals to control its many functions, similar to how traffic lights control the flow of cars.
One type of these signals, known as gamma oscillations, plays a critical role in cognitive processes like working memory—the kind of memory that helps you remember things like a phone number.
In people with early signs of Alzheimer’s disease, these gamma oscillations are often weakened.
In previous attempts, researchers have tried using external tools, such as sound waves or magnetic stimulation, to increase gamma oscillations.
While these methods helped dissolve brain plaques, they didn’t significantly improve memory. Mody and his team wanted to take a different path—finding a way to trigger these brain rhythms from within using a specially designed molecule.
They discovered that certain neurons, known as parvalbumin interneurons, are key to generating gamma oscillations.
However, in Alzheimer’s disease, these neurons are less active due to a chemical imbalance involving a neurotransmitter called GABA. Essentially, the neurons are not firing as they should because GABA acts like a brake, preventing strong gamma oscillations.
To address this, the researchers developed DDL-920, a compound designed to block GABA from inhibiting these neurons. By doing so, the drug allows the neurons to produce more robust gamma oscillations, which in turn helps improve memory and cognition.
The team tested this molecule on mice that were genetically modified to have Alzheimer’s-like symptoms. These mice, along with healthy mice, were put through a series of memory tests using a Barnes maze, which is a circular platform with visual clues to help the mice find an escape hole.
Before receiving DDL-920, the Alzheimer’s mice had difficulty remembering the location of the escape hole. But after being treated with the drug for two weeks, these mice performed almost as well as the healthy mice, showing significant improvements in their memory.
Importantly, the treated mice did not show any signs of abnormal behavior or side effects during the study, which suggests that DDL-920 could be safe, at least in mice.
However, Dr. Mody cautioned that much more research is needed to determine whether the drug would be safe and effective for humans.
If further studies in humans are successful, this new drug could offer hope not only for people with Alzheimer’s disease but also for those with other conditions that affect gamma oscillations, such as depression, schizophrenia, and autism.
“We are very enthusiastic about this because it’s a completely novel approach that hasn’t been explored before,” Dr. Mody said.
This discovery represents an exciting step forward in the search for better treatments for Alzheimer’s and other neurological disorders.
Although there is still a long road ahead, the potential of DDL-920 to restore memory function offers new hope in the fight against one of the most devastating diseases affecting millions of people worldwide.
If you care about Alzheimer’s disease, please read studies about the protective power of dietary antioxidants against Alzheimer’s, and eating habits linked to higher Alzheimer’s risk.
For more information about brain health, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
The research findings can be found in PNAS.
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