Researchers have developed an effective drug to specifically inhibit the tau protein, the accumulation of which in the brain is characteristic of Alzheimer’s disease.
- Tau proteins play a crucial role in maintaining the structure and function of neurons, but in Alzheimer’s disease, these proteins malfunction and accumulate abnormally in the brain.
- The new drug, a peptide inhibitor called RI-AG03, differs from current treatments by simultaneously inhibiting two “hot spots” on the tau protein, where it tends to clump together.
- Tested in the laboratory on Drosophila flies modified to develop the disease, RI-AG03 helped slow neurodegeneration and extend their life expectancy. It must now be tested on rodents.
This is a promising breakthrough in the search for treatment against Alzheimer’s disease. For the first time, an international team of scientists has developed a drug in the laboratory targeting two specific areas of the tau protein, known to play a central role in neurodegeneration. Their work was published in the journal Alzheimer’s & Dementia.
Inhibit two specific regions on the tau protein
Tau proteins play a crucial role in maintaining the structure and function of neurons, but in Alzheimer’s disease, these proteins malfunction and accumulate abnormally in the brain. These clumps form neurofibrillary tangles that prevent neurons from functioning properly. As more and more neurons die, memory, thinking, and behavior become increasingly impaired, hence the cognitive decline seen in Alzheimer’s patients.
The drug in question, a peptide inhibitor called RI-AG03, differs from current treatments by simultaneously targeting two “hot spots” on the tau protein, where it tends to clump together. “There are two regions of tau that act like a zipper to allow it to aggregate. For the first time, we have an effective drug to inhibit both of these regions at the same time.”explains Dr. Anthony Aggidis, lead author of the study, in a press release.
The new therapeutic approach is intended “safer”continues the researcher. “We know that the toxicity of tau is intimately linked to its ability to aggregate, but current aggregation inhibitors have had many side effects because they can interfere with the functions of many other proteins.” RI-AG03 is specifically designed against tau, meaning it is less likely to interact undesirably with other proteins.
Towards potential treatments for Alzheimer’s disease
Tested in the laboratory, the drug demonstrated its effectiveness on models of Drosophila flies, modified to develop the disease. RI-AG03 was able to slow down neurodegeneration and extend their life expectancy by two weeks, a significant reprieve given the lifespan of insects. “The higher the dosage given, the greater the improvement in life expectancy”specify the scientists.
Tests on human cells also confirmed that this drug effectively reduced the accumulation of tau protein. The research team now plans to test the drug on rodents, before considering clinical trials on humans, thus paving the way for potential treatments for neurodegenerative diseases such as Alzheimer’s.
