Compound discovered to restore cognitive function and memory in Alzheimer's patients, potentially leading to treatments for schizophrenia and depression

A research team at the University of California, Los Angeles School of Medicine has reported that they have discovered a compound that restores cognitive function and memory in Alzheimer's patients. The research team has demonstrated the effect in experiments using mice, and says that if the effect is proven in humans, it could be applied to the treatment of Alzheimer's disease, schizophrenia, and depression.

A therapeutic small molecule enhances γ-oscillations and improves cognition/memory in Alzheimer's disease model mice | PNAS
https://www.pnas.org/doi/10.1073/pnas.2400420121

Molecule restores cognition, memory in Alzheimer's disease model mice | UCLA Health
https://www.uclahealth.org/news/release/molecule-restores-cognition-memory-alzheimers-disease-model

In the brain, electrical signals fire at different rhythms to start and stop various functions. Among them, gamma oscillations are one of the highest frequency rhythms and are known to control brain circuits underlying cognitive processes and working memory. In addition, it has been shown that gamma oscillations are reduced in patients with early symptoms of Alzheimer's disease.

The research focused on finding a molecule called DDL-920 that reactivates memory circuits in the brain by targeting interneurons that play a key role in generating gamma oscillations, preventing the activation of certain chemical receptors.

'The receptors are normally activated by a chemical messenger called GABA ( gamma-aminobutyric acid ), which acts like a brake to suppress gamma oscillations. But by suppressing their activation, DDL-920 allows interneurons to generate stronger, sustained gamma oscillations. This could help restore cognitive function and memory,' the team said.

The study involved genetically altering mice that showed symptoms of Alzheimer's disease, and testing both these mice and normal mice in the Barnes maze to assess their learning and memory abilities.

The researchers administered DDL-920 to mice with Alzheimer's disease for two weeks, and found that the mice were able to escape the maze at the same rate as normal mice, and did not show any abnormal behavior, hyperactivity, or other visible side effects.

The researchers showed that the treatment was effective in mice, but stress that more research is needed to confirm its safety and efficacy in humans. If ultimately proven effective in humans, the drug could potentially be used to treat not only Alzheimer's disease, but also other diseases and conditions in which gamma oscillations are reduced, such as depression, schizophrenia, and autism spectrum disorder.

'There is no such treatment on the market and none that have been experimentally proven to have this effect,' said Professor Istvan Modi, lead author of the study. 'Our research is new and deals with a mechanism of action that has not been studied before, so we are working extremely hard on this research.'