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Lancaster, UK — An international team of scientists led by Lancaster University has made significant strides in Alzheimer’s disease research with the development of a novel dual-action drug known as RI-AG03. This peptide inhibitor uniquely targets two critical aggregation-promoting “hotspots” on the Tau protein, a major contributor to neurodegeneration in Alzheimer’s patients. The findings were published on October 3 in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Targeting Tau: A Key to Alzheimer’s
Tau proteins are essential for maintaining the structure and function of neurons, but they can become dysfunctional in Alzheimer’s disease, leading to the formation of neurofibrillary tangles. These tangles, composed of twisted Tau proteins, impede neuronal function and contribute to cognitive decline. Current treatments often target only one aggregation site on the Tau protein, leaving a significant gap in therapeutic efficacy.
Lead author Dr. Anthony Aggidis, a former Postdoctoral Research Associate at Lancaster University, highlighted the importance of this discovery, stating, “By targeting both of the key areas on the Tau protein, this unique approach could help address the growing impact of dementia on society.”
A Dual-Target Strategy
RI-AG03 was developed by Dr. Aggidis and tested in laboratory settings under the guidance of the late Professor David Allsop. The drug demonstrated efficacy in inhibiting Tau protein aggregation in both lab dishes and in fruit fly models engineered to express pathogenic Tau.
Professor Amritpal Mudher from the University of Southampton noted, “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.”
Safer, More Effective Treatment
The peptide-based approach of RI-AG03 offers a more targeted treatment strategy compared to existing therapies, potentially resulting in fewer side effects. Dr. Aggidis explained that by specifically inhibiting Tau protein aggregation, RI-AG03 is less likely to interfere with other proteins, a common issue with many current aggregation inhibitors.
Promising Results from Testing
The drug’s effectiveness was further validated through experiments conducted at the University of Southampton, where fruit flies with pathogenic Tau were treated with RI-AG03. The researchers observed a significant suppression of neurodegeneration and an extension of the flies’ lifespans by approximately two weeks, a notable achievement given their short life expectancy.
Moreover, the team at the University of Texas Southwestern Medical Center tested RI-AG03 in engineered human cell lines and found similar results, confirming the drug’s ability to penetrate cells and reduce Tau protein aggregation.
Future Directions
The researchers are optimistic about the implications of their work for drug discovery in neurodegenerative diseases and are planning to advance RI-AG03 into rodent trials, eventually leading to clinical studies.
Dr. Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society UK, which funded the research, emphasized the importance of this breakthrough. “This research is taking promising steps towards a new one-of-a-kind therapy which targets Tau, a damaging protein in the brains of people living with Alzheimer’s.”
While acknowledging that the study is still in its early stages, Oakley expressed hope that RI-AG03 could lead to a safer and more effective treatment option for Alzheimer’s patients.
The study represents a significant step forward in the ongoing battle against Alzheimer’s disease, providing renewed hope for patients and their families. As the research progresses, experts call for increased funding and partnerships to further accelerate advancements in dementia research.
Reference: “A novel peptide-based Tau aggregation inhibitor as a potential therapeutic for Alzheimer’s disease and other Tauopathies,” Alzheimer’s & Dementia, October 3, 2024. DOI: 10.1002/alz.14246.
