Researchers have developed a new drug that holds promise in Alzheimer's treatment by blocking tau-build-up, acting at two regions of the protein, preventing it from sticking together.
The latest drug, RI-AG03, is a peptide inhibitor developed by a research team led by Lancaster University in collaboration with the University of Southampton, Nottingham Trent University, Tokyo Metropolitan Institute of Medical Science, and the University of Texas Southwestern Medical Center.
In studies conducted in both the lab and with fruit flies, RI-AG03 was found to prevent the buildup of tau proteins, which play a key role in Alzheimer's disease and other neurodegenerative disorders. The results were published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
"There are two regions of the Tau protein that act like a zipper to enable it to aggregate. For the first time, we have a drug that is effective in inhibiting both these regions. This dual-targeting mechanism is significant because it addresses both domains that stimulate Tau aggregation, potentially paving the way for more effective treatments for neurodegenerative diseases like Alzheimer's," Amritpal Mudher, a researcher of the study from the University of Southampton said in a news release.
Current treatments typically focus on one of the hotspots associated with tau buildup. However, researchers said RI-AG03 is unique as it simultaneously targets and blocks both hotspots. Since the current approach targets the peptide, it is considered safer, with fewer side effects.
The current aggregation inhibitors often cause side effects as they can disrupt the functions of various proteins in the body. In contrast, RI-AG03 is specifically designed to target the tau protein, making it less likely to interact negatively with other proteins, researchers explained.
In the fruit fly study, researchers observed that the drug suppressed neurodegeneration and extended the flies' lifespan by about two weeks. This is a significant finding, especially given the short lifespan of these insects.
To see if the positive effects observed in fruit flies were limited to that species, researchers tested the drug on a biosensor cell, a specialized human cell line designed to detect the formation of tau fibrils. The results showed that the drug successfully penetrated the cells and reduced the aggregation of tau proteins.
"Our research represents an important step toward creating treatments that can prevent the progression of diseases like Alzheimer's disease. By targeting both of the key areas on the tau protein, this unique approach could help address the growing impact of dementia on society, providing a much-needed new option for treating these devastating diseases," said lead author Dr. Anthony Aggidis in a news release.
