Instead of trying to eliminate the beta-amyloid protein, like most current medications, the new drug restores the cell’s own ability to eliminate toxic proteins.
An experimental new drug appears to halt brain degeneration even before the onset of symptoms of Alzheimer’s appear. The treatment, known as NU-9, has shown impressive results in mouse models of Alzheimer’s.
Most existing Alzheimer’s treatments, such as donanemab and lecanemab, focus on beta-amyloid protein eliminationwhich accumulates in the brains of people with Alzheimer’s. Although beta-amyloid has long been considered central to the disease, many scientists now believe that Alzheimer’s is driven by multiple overlapping processes, which may explain why current therapies have had limited success.
The NU-9 takes a different approach. Although it still targets the beta-amyloid protein, it works by restoring the cell’s own ability to eliminate toxic proteins. According to William Kleinprofessor of neurobiology and author of the published in Alzheimer’s & Dementia, nerve cells normally have mechanisms to rid themselves of the accumulation of harmful proteins, but these systems fail in neurodegenerative diseases such as Alzheimer’s and amyotrophic lateral sclerosis (ALS). “The NU-9 is rescuing the pathway that saves the cell“, explained Klein.
The timing of the administration appears to be crucial. In the study, researchers administered NU-9 to genetically modified mice before they showed any symptoms of Alzheimer’s. Over 60 days of daily oral treatment, the medication prevented many of the characteristic changes observed at the beginning of the disease. “By the time symptoms emerge, the underlying pathology is already advanced,” said the lead author, Daniel Kranznoting that late intervention may be the reason why many previous clinical trials failed.
The team also identified a previously unknown subtype of highly toxic beta-amyloid protein that forms within neurons and nearby support cells, called astrocytes, in the early stages of the disease. These protein clusters, known as ACU193+ oligomers, appear to trigger inflammation and cellular dysfunction. The NU-9 significantly reduced levels of these toxic proteins and attenuated inflammatory responses in the brain.
Notably, the medicine also reduced TDP-43 levelsanother abnormal protein associated with cognitive decline and ALS, suggesting that NU-9 may have broader neuroprotective effects, writes .
Although the results are limited to animal models, researchers believe that the combination of early diagnosis and treatment can be transformative. Blood tests to detect Alzheimer’s disease before symptoms appear are already in development, paving the way for preventive therapies.
