A new compound could revolutionize the treatment of Alzheimer's disease.
Researchers at the University of California, Los Angeles (UCLA) have developed a molecule capable of restoring cognitive functions and memory in mouse models of the disease. This breakthrough marks a departure from traditional approaches that focus on removing amyloid plaques from the brain, which are often deemed responsible for the disease's symptoms.
For a long time, Alzheimer's treatments have aimed at reducing the accumulation of beta-amyloid protein plaques in the brain, according to the "amyloid cascade" theory. Although these treatments slow the progression of the disease, they fail to reverse existing cognitive impairments. Istvan Mody, a professor of neurology and physiology at UCLA, emphasizes that these treatments may leave the brain "perhaps without plaques," but with neural circuits still impaired.
In light of this, Istvan Mody and his team have developed a new compound called DDL-920, which targets a different biomolecular mechanism. Their approach is based on stimulating gamma oscillations, high-frequency electrical signals essential for memory and cognitive functions. These oscillations are generated by fast-spiking interneurons, the parvalbumin neurons, which play a crucial role in activating neural circuits involved in cognitive processes. However, in Alzheimer's patients, these oscillations are often reduced, even before amyloid plaques begin to alter the brain.
Earlier studies attempted to restore these gamma oscillations through auditory or visual stimulations, but the results were inconclusive in terms of cognitive improvement. Therefore, Istvan Mody and colleagues explored a pharmacological avenue. By inhibiting the receptors that reduce gamma oscillations, DDL-920 would allow neurons to function more efficiently, thereby restarting the oscillations necessary for memory.
To test the effectiveness of this molecule, researchers administered DDL-920 to mice genetically modified to reproduce Alzheimer's disease symptoms. After two weeks of treatment, the treated mice showed cognitive performance comparable to healthy mice in a maze test. Furthermore, no behavioral anomalies were observed.
Although these results are promising, further research is necessary to confirm the safety and effectiveness of this treatment in humans. If these studies prove successful, this compound could pave the way for new therapies for other diseases associated with reduced gamma oscillations, such as depression and schizophrenia.
Article author: Cédric DEPOND