Drugs in experiment could stop toxic protein buildup

• Scientists have developed a new drug that targets two key regions of the tau protein, the main cause of Alzheimer's disease.
• The drug, a peptide inhibitor called RI-AG03, was successful in preventing the accumulation of toxic tau proteins both in the lab and in Drosophila studies.
• Although further research is needed, including clinical trials in humans, this research will contribute to the advancement of more effective treatments for neurodegenerative diseases.

Tau protein is essential for maintaining neuron structure and function. however, alzheimer's diseasethese proteins become dysfunctional and aggregate into long, twisted fibrils.

When these fibrils accumulate, they form neurofibrillary tangles, or clumps of neurofibrillary tangles. tangled tau protein It blocks neurons from receiving necessary nutrients and signals.

This leads to the death of nerve cells, resulting in progressive memory loss, cognitive impairment, and behavioral changes characteristic of Alzheimer's disease.

Recent research published in Alzheimer's disease and dementiaexperimented with a new method to potentially prevent the accumulation of toxic tau in the brain.

The study was conducted by researchers at the University of Southampton in collaboration with Lancaster University, Nottingham Trent University (both in the UK), the Tokyo Metropolitan Institute of Medical Research in Japan, and Southwestern Medical Center in Texas.

The tau protein has two major “hot spots” where fibril aggregation occurs. In this new study, the researchers developed a drug that targets both of these “hot spots” in the tau protein.

Existing treatments focus on one or the other, but RI-AG03 is the first drug to target and inhibit both.

The drug is a peptide inhibitor that has been successful in preventing tau protein accumulation both in the laboratory and in Drosophila studies.

Dr. Anthony Agidislead author and visiting researcher at the University of Southampton, described the key findings. Today's medical news.

“In Alzheimer's disease, there are proteins in the brain that aggregate and malfunction. These aggregates are toxic to the brain, killing brain cells and causing memory loss and thinking disorders. We have developed a drug that is effective in targeting both critical regions of this protein that are responsible for protein aggregation.”

The study details how RI-AG03 was first developed by Agidis in his late lab. Dr. David Alsopusing computational biology at Lancaster University, was first tested in a laboratory dish.

To assess its effectiveness in living organisms, researchers at the University of Southampton administered the drug to fruit flies carrying pathogenic tau.

“We found that this drug suppresses neurodegeneration and extends lifespan. [approximately] 2 weeks in a fruit fly [that] They were bred to produce this malfunctioning human protein,” Agidis explained. “This is a significant extension when you consider the lifespan of insects.”

“While testing in Drosophila may seem strange, the biological processes involving this protein are conserved across species, and the use of these models is well established,” he added. .

When the researchers examined Drosophila brains, they found that flies given the peptide inhibitor had large numbers of pathogenic tau fibrils, but flies treated with the drug had significantly fewer of these fibrils. I discovered that

The higher the dose, the longer and improved the lifespan of the flies.

To confirm that this effect is not limited to Drosophila, researchers at UT Southwestern Medical Center developed a biosensor, a type of human cell line, engineered to detect tau fibril formation. We tested RI-AG03 in cells.

The drug successfully penetrated these cells and reduced tau aggregation.

Dr. James Giordanosaid Georgetown University Medical Center's Pellegrino Center Professor of Neurology and Biochemistry, who was not involved in the study. MNT “This is an interesting, well-conceived and well-executed study that describes the development of a novel pharmacological agent, RI-AGO3.”

The drug “inhibits the aggregation of tau proteins, which may contribute to pathogenic changes in neurodegenerative diseases such as Alzheimer's disease.” [disease]” he explained.

“Using both in vitro and in vivo models, this new drug is able to reduce tau protein aggregation by targeting two different sites and mechanisms that act on tau proliferation, while simultaneously “We can expect it to be non-toxic,” Giordano said.

Professor Giordano explained: “This study adds to previous and ongoing research, including our own research. [firstly,] Tau protein acts on Alzheimer's disease, [secondly, the] Inhibition of tau protein aggregation may be an important element in the development of interventions that may reduce the onset and progression of certain neurodegenerative diseases. ”

“Although this study is preliminary, the results demonstrated in both in vitro and in vivo models support the potential value of this study and related compounds in clinical therapy,” he added. I did.

Although further research is needed, the research team believes these findings will have a major impact on drug discovery in the field of neurodegenerative diseases.

As a result, they now plan to test RI-AG03 in rodents before moving to clinical trials.

“This drug is currently in preclinical testing. However, we believe this research can have a major impact on drug discovery efforts in disease areas such as Alzheimer's disease and improve patient outcomes.” We will conduct additional preclinical studies over the next few years before considering the trial and how it will impact patients.”

– Dr. Anthony Agidis

but, Clifford Segill DOA neurologist at Providence St. John's Health Center in Santa Monica, Calif., who was not involved in the study, also said, “Tau-based disease-modifying therapies have so far failed to yield therapeutic drugs.'' “I have no expectations for this study.” To create new neurological treatments. ”

“Even if tau aggregation inhibitors are found to be functional and safe, they still need to be studied to see if they can cause clear clinical improvement in patients with neurological symptoms,” Segil said. he added.

Although these early discoveries are promising, it is important to note that drug development is a long process and human clinical trials are essential to determining the safety and effectiveness of potential treatments. That is important.