Northwestern researchers have discovered that an experimental drug called NU-9 shows promise as an early intervention for Alzheimer’s disease. Invented by Richard Silverman, the Patrick G. Ryan/Aon Professor of Chemistry, NU-9 is a small molecule compound that is currently being tested as a treatment for ALS, known as Lou Gehrig’s disease. A new study shows that NU-9 also improves neuron health in animal models of Alzheimer’s.
“In both ALS and Alzheimer’s disease, cells suffer from toxic protein buildup,” says neurobiology professor William Klein, who worked on the study alongside Silverman and Daniel Kranz ’25 PhD. “Cells have a mechanism to get rid of these proteins, but it gets damaged in degenerative diseases like ALS and Alzheimer’s. NU-9 is rescuing the pathway that saves the cell,” Klein says.
The team sought to evaluate the drug’s effectiveness at halting the earliest signs of Alzheimer’s. The scientists identified a previously unknown, highly toxic subtype of amyloid beta oligomers — toxic clusters of peptides — called ACU193+ that appear to drive some of the brain’s earliest changes in Alzheimer’s. The presence of those clusters “potentially acts as an instigator of early Alzheimer’s pathology,” says Kranz, the study’s lead author.
ACU193+ oligomers bind to astrocytes — star-shaped brain cells that protect neurons and control inflammation. When that occurs, the astrocytes are pushed into a reactive and highly destructive state, releasing inflammatory molecules, damaging synapses and accelerating neurodegeneration. Stopping this process might be one of the most powerful ways to slow Alzheimer’s progression, the researchers say.
In the study, the researchers administered NU-9 to a presymptomatic mouse model of Alzheimer’s and found that the compound significantly decreased the number of ACU193+ oligomers bound to astrocytes. As a result, the drug mitigated the inflammatory reaction of astrocytes, dramatically reducing neurological damage. They also saw a decrease in an abnormal form of TDP-43, a protein that is a hallmark of neurodegenerative diseases.
The findings point to a potential new strategy for treating Alzheimer’s before cognitive decline and other debilitating symptoms begin.
Silverman compared the strategy to early intervention approaches for heart disease.
“People are used to monitoring their cholesterol,” Silverman says. “If you have high cholesterol, it doesn’t mean that you will have a heart attack soon. But it’s time to take drugs to lower your cholesterol to prevent [a heart attack] down the road. NU-9 could play a similar role. If someone has a biomarker signaling Alzheimer’s, they could start taking NU-9 before symptoms appear.”
In 2024 the U.S. Food and Drug Administration approved human clinical trials using NU-9 for the treatment of ALS. NU-9 has not yet received clearance for clinical trials addressing Alzheimer’s.
The team is currently testing NU-9 in additional animal models of Alzheimer’s, including a model of late-onset disease that better reflects typical human aging. The researchers also plan to examine how early intervention with NU-9 affects memory and neuron health over time.
“There are a couple early diagnostic blood tests for Alzheimer’s disease in development,” Klein adds. “Better early diagnostics — combined with a drug that could stop the disease in its tracks — is the goal.
Editor’s note: Silverman is founder of, and has financial interests in, Akava Therapeutics, a startup company that is commercializing NU-9 (now called AKV9). Klein is co-founder of, and has financial interests in, Acumen Pharmaceuticals, which developed a therapeutic monoclonal antibody currently in clinical trials that targets the subtype of amyloid beta oligomers identified in this study. The University has financial interests (equities, royalties) in both companies.
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