New Delhi, Oct 3 (VOICE) In a promising breakthrough, an international team of researchers from the UK, US, and Japan has developed a new Alzheimer’s drug that effectively prevents the build-up of Tau proteins — a key driver of neurodegeneration.The drug, a peptide inhibitor called RI-AG03 blocked both Tau aggregation ‘hotspots’ for the first time in both lab and fruit fly studies.
While Tau proteins play a crucial role in maintaining the structure and function of brain cells, these, however, malfunction in Alzheimer’s disease. The proteins clump together to form long and twisting fibrils, which when accumulated create neurofibrillary tangles.
The masses of twisted Tau proteins then clog the brain cells, preventing them from getting the nutrients leading to their death. The more brain cells die, memory, thinking, and behaviour becomes increasingly impaired, leading to the cognitive decline seen in Alzheimer’s.
The research, published in the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, focussed on two specific ‘hotspots’ of the Tau protein where this clumping tends to happen.
While current treatments target one or the other of these hotspots, RI-AG03 uniquely targets and blocks both.
“There are two regions of the Tau protein that act like a zipper to enable it to aggregate,” said lead author Amritpal Mudher, Professor of Neuroscience at the University of Southampton.
“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,” she added.
RI-AG03 was developed using computational biology and tested in lab dishes.
To test its effectiveness in cells within a living organism, the researchers gave the drug to fruit flies that had pathogenic Tau. The researchers found the drug suppressed neurodegeneration and extended the lives of the flies by around two weeks — a significant extension considering the life span of the insects.
In fruit flies fed with RI-AG03, “the pathogenic fibrils decreased significantly in quantity,” Mudher said, with a higher dose showing a “greater improvement in the fruit fly’s lifespan.”
Further, the researchers tested the drug in a biosensor cell — a type of living human cell line that is engineered to detect pathogenic tau fibril formation.
Here too, the drug successfully penetrated the cells and reduced the aggregation of Tau proteins.
The team believes their work will have a significant impact on drug discovery efforts in the field of neurodegenerative diseases and now plans to test RI-AG03 in rodents, before proceeding to clinical trials.
–VOICE
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