A new drug could stop Alzheimer’s before memory loss begins
New research suggests Alzheimer’s may start far earlier than previously thought, driven by a hidden toxic protein in the brain. Scientists found that an experimental drug, NU-9, blocks this early damage in mice and reduces inflammation linked to disease progression. The treatment was given before symptoms appeared, targeting the disease at its earliest stage. Researchers say this approach could reshape how Alzheimer’s is prevented and treated.
An experimental drug developed at Northwestern University has demonstrated further promise as an early intervention for Alzheimer's disease.
In a new study, Northwestern scientists identified a previously unknown highly toxic sub-species of amyloid beta oligomers -- toxic clusters of peptides -- that appear to drive several of the brain's earliest changes, including neuronal dysfunction, inflammation and activation of immune cells.
The experimental drug, a small-molecule compound called NU-9, decreased this toxic amyloid beta oligomersubtype and dramatically reduced the damage it causes in a mouse model of Alzheimer's disease. By addressing these changes at the onset of Alzheimer's disease, the researchers are hopeful NU-9 potentially could prevent, or significantly delay, the cascade of toxic events that ultimately destroy neurons.
The findings point to a potential new strategy for targeting the disease in its earliest stages -- before cognitive decline and other debilitating symptoms take hold.
The study will be published on Dec. 18 in Alzheimer's and Dementia: The Journal of the Alzheimer's Association.
"Alzheimer's disease begins decades before its symptoms appear, with early events like toxic amyloid beta oligomers accumulating inside neurons and glial cells becoming reactive long before memory loss is apparent," said Northwestern's Daniel Kranz, the study's first author. "By the time symptoms emerge, the underlying pathology is already advanced. This is likely a major reason many clinical trials have failed. They start far too late. In our study, we administered NU-9 before symptom onset, modeling this early, pre-symptomatic window."
Kranz is a recent Ph.D. graduate from the Interdisciplinary Biological Sciences (IBiS) program at Northwestern's Weinberg College of Arts and Sciences, where he is advised by corresponding author William Klein. An expert on Alzheimer's disease, Klein is a professor of neurobiology at Weinberg and a cofounder of Acumen Pharmaceuticals, which has developed a therapeutic monoclonal antibody currently in clinical trials that targets the subtype of amyloid beta oligomers identified in the study. Richard Silverman, a key co-author of the study, invented NU-9. Silverman, who previously invented pregabalin (Lyrica) to treat fibromyalgia, nerve pain and epilepsy, is the Patrick G. Ryan/Aon Professor in Weinberg's Department of Chemistry and founder of Akava Therapeutics, a startup company commercializing NU-9 (now called AKV9).
The promise of NU-9
Conceived about 15 years ago, NU-9 emerged as part of Silverman's multi-year effort to discover a small molecule compound that could prevent toxic protein aggregate buildup in neurodegenerative diseases. By 2021, NU-9 demonstrated efficacy in animal models of amyotrophic lateral sclerosis (ALS), clearing toxic SOD1 and TDP-43 proteins and restoring health to upper motor neurons. In 2024, it received clearance from the U.S. Food and Drug Administration to begin human clinical trials for ALS.