Northwestern scientists report that NU-9, a small molecule (cyclohexane-1,3-dione), reduced a newly identified subtype of amyloid-beta oligomers (ACU193+ AβOs) and associated inflammation in mice predisposed to Alzheimer’s after 60 days of oral dosing. The study suggests NU-9 could become a preventive treatment paired with early blood diagnostics, but results are preliminary and limited to animal models. Next steps include testing efficacy in later-stage disease models and progressing toward human safety and clinical trials.
NU-9 Halts Early Alzheimer’s Changes in Mice — A Potential Preventive Drug Like Cholesterol Medicine
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Northwestern University researchers report that a novel small molecule, NU-9, stopped early Alzheimer’s-related brain changes in a mouse model by targeting a newly identified subtype of toxic amyloid-beta oligomers. The findings, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, raise the possibility that a preventive, biomarker-driven treatment could one day control Alzheimer’s risk much like cholesterol-lowering drugs manage heart disease risk.
What The Team Did
The researchers gave oral NU-9 to laboratory mice genetically predisposed to develop Alzheimer’s but not yet symptomatic. Treatment continued for 60 days while investigators monitored effects on amyloid-beta oligomers — small, soluble protein aggregates implicated in the earliest stages of Alzheimer’s disease.
Key Findings
Detailed examination of brain tissue showed that NU-9 substantially reduced a previously unrecognized subtype of amyloid-beta oligomers the team labeled ACU193+ AβOs. These oligomers were associated with early brain inflammation. Mice treated with NU-9 had lower levels of this toxic protein species and reduced markers of neuroinflammation compared with untreated controls.
“These results are stunning,” said William Klein, the study’s principal investigator and a neuroscience professor at Northwestern. Richard Silverman, the chemist who developed NU-9, compared the approach to treating high cholesterol: if a blood biomarker indicates elevated risk, a preventive drug could be started before symptoms appear.
About NU-9
NU-9 (chemical name: cyclohexane-1,3-dione) was synthesized by Richard Silverman in a search for compounds that can target pathological proteins in neurological diseases. In addition to the Alzheimer’s mouse data, the compound has shown activity in preclinical models of amyotrophic lateral sclerosis (ALS) and possibly frontotemporal degeneration — disorders that also involve toxic protein accumulation in the brain.
Limitations And Next Steps
These results are limited to a preclinical mouse model. The effect of NU-9 in later-stage disease and in humans remains unknown. The researchers plan to test NU-9 in models of more advanced Alzheimer’s to see whether it can slow or reverse progression after symptoms appear. Clinical development would require safety testing, dose optimization, and human trials to confirm efficacy and tolerability.
Why It Matters
If future studies validate these findings in humans, a drug that targets a specific toxic oligomer and is paired with early blood diagnostics could shift Alzheimer’s care toward prevention — treating at-risk individuals before cognitive decline begins. Until then, the findings represent an important step in understanding disease mechanisms and identifying therapeutic targets.
