Breakthrough Alzheimer’s drug offers new hope to millions worldwide

Researchers from Lancaster University and international collaborators have taken a significant step forward in developing a drug to treat Alzheimer's disease. Their new peptide inhibitor, called RI-AG03, has been shown to prevent the build-up of harmful Tau proteins in the brain, a major factor in neurodegeneration.

This breakthrough offers new hope for more effective treatments in the fight against Alzheimer’s, which affects millions worldwide.

Tau proteins normally help maintain the structure and function of neurons in the brain. However, in people with Alzheimer's disease, these proteins begin to malfunction. They aggregate, or clump together, forming long strands known as fibrils.

These fibrils further twist into neurofibrillary tangles, which block neurons from receiving essential nutrients and signals, eventually leading to neuron death. As neurons die, cognitive functions like memory and behavior deteriorate, resulting in the progressive decline associated with Alzheimer’s.

What sets RI-AG03 apart is its ability to target both key aggregation-promoting areas of the Tau protein. Current treatments focus on just one of these regions, but RI-AG03’s dual-targeting mechanism marks a first in Alzheimer’s research. This could lead to more effective treatments that address the root cause of cognitive decline more comprehensively.

According to Dr. Anthony Aggidis, the lead author and former postdoctoral research associate at Lancaster University, “Our research represents an important step toward creating treatments that can prevent the progression of diseases like Alzheimer’s.”

The effectiveness of RI-AG03 was demonstrated in lab studies and tested in living organisms, including fruit flies genetically modified to exhibit Alzheimer’s-like symptoms. Researchers found that administering RI-AG03 to the flies significantly suppressed neurodegeneration and extended their lifespans by around two weeks, a considerable amount of time given the short life expectancy of these insects. Scientists also observed a decrease in pathogenic Tau fibrils in the brains of the treated flies.

The drug’s impact wasn’t limited to flies. Researchers at the University of Texas Southwestern Medical Centre tested RI-AG03 on human cell lines specifically engineered to detect Tau protein aggregation. Here, too, the drug successfully reduced the formation of Tau fibrils, suggesting it can penetrate living cells and target the protein effectively.

Professor Amritpal Mudher of the University of Southampton, one of the study’s collaborators, emphasized the significance of the dual-targeting approach: “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 which 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.”

This more targeted approach offers potential benefits beyond its effectiveness in reducing Tau build-up. RI-AG03 could be safer than current treatments, which often come with side effects. Dr. Aggidis explained that because Tau toxicity is linked to its ability to aggregate, inhibiting this aggregation should have positive effects.

However, current treatments that inhibit protein aggregation can interfere with other proteins in the body, leading to side effects. RI-AG03 was designed specifically to target Tau, meaning it’s less likely to interact negatively with other proteins, which could make it a safer option.

The development of RI-AG03 took years of research, beginning with work done by Dr. Aggidis in the laboratory of the late Professor David Allsop at Lancaster University. The project is a testament to the combined efforts of institutions worldwide, including the University of Southampton, Nottingham Trent University, and the Tokyo Metropolitan Institute of Medical Science.

The research has been published in the prestigious journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

While the current studies have demonstrated success in both fruit flies and human cell lines, further research is planned to advance RI-AG03’s potential as a treatment. Next steps involve testing the drug in rodents before moving on to clinical trials in humans. These upcoming trials will be crucial in determining the drug’s safety and efficacy in people.

Dr. Richard Oakley, Associate Director of Research and Innovation at the Alzheimer’s Society UK, commented on the importance of this research. “Dementia is the UK’s biggest killer, and it applies enormous cost and pressure to our healthcare system, which is why we’re committed to funding world-leading studies like this one. 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, preventing it from clumping together,” said Dr. Oakley.

He added, “It’s important to note that the study is in its early stages, so we don’t yet know if it will work or be safe for humans, but it’s an exciting development and we look forward to seeing where it leads.”

As researchers prepare for the next phase of testing, this breakthrough brings renewed hope for families affected by Alzheimer’s and related neurodegenerative diseases. With further research and funding, RI-AG03 could one day offer a new treatment option for a condition that has long defied effective intervention.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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