by Brains affected by Alzheimer’s disease are characterized by harmful clumps and tangles that disrupt neurons – but a new study describes a drug that could potentially suppress half of the problem.
The drug is RI-AG03 and it is a peptide inhibitor (a blocker of proteins). Tests on fruit flies and human cells have shown that it has a positive effect on reducing the degeneration of neurons and the tangling of tau proteins. In the case of the fruit flies, the lifespan of the insects was extended by as much as 35 percent.
What makes RI-AG03 special, according to the international team of researchers behind the study, is the way it targets two specific ‘hotspots’ on tau proteins where clumping often occurs, producing long and winding threads called fibrils .
“There are two regions of the tau protein that act like a zipper, allowing it to aggregate,” says neuroscientist Amritpal Mudher of the University of Southampton in Britain. “For the first time, we have a drug that is effective at inhibiting both regions.”
“This dual-targeting mechanism is important because it addresses both domains that drive tau aggregation, potentially paving the way for more effective treatments for neurodegenerative diseases such as Alzheimer’s.”
Tau proteins in the brain are not all bad. When healthy, they help maintain the stability of the different branches of a neuron. But in some Alzheimer’s brains – either as a cause or as a result of the disease – their fibrils go into overdrive.
The RI-AG03 drug was produced using computational biology techniques to specifically target both fibril zones on the tau protein. The effectiveness it has shown in these experiments is evidence of successful drug design – even if there is still much work to be done before it can be used in humans.
And because of the specific way RI-AG03 is designed, it is precisely targeted. When it comes to trying to make drug-induced changes in the brain, it is crucial that no collateral damage occurs in this most delicate of systems.
“Current aggregation inhibitors have had many side effects because they can disrupt the functions of many other proteins,” says neuroscientist Anthony Aggidis of the University of Southampton.
“RI-AG03 is specifically designed against the tau protein, meaning it is less likely to interact undesirably with other proteins.”
The next phase for this particular drug is testing on mice, and then clinical trials can begin. But while many tau-based therapies have shown success in animal models, many have so far failed to deliver clinical benefits in humans.
“Our research represents an important step toward creating treatments that can prevent the progression of diseases like Alzheimer’s,” says Aggidis.
“By targeting both key areas of the tau protein, this unique approach could help address the growing impact of dementia on society, and provide a much-needed new option for treating these devastating diseases.”
The research was published in Alzheimer’s and dementia.
