Researchers from Northwestern University discovered that in animal models of Alzheimer’s disease, NU-9, an FDA-approved experimental drug for ALS clinical trials, efficiently lowers harmful protein accumulation. Animal studies have shown that NU-9 has two advantages: it reduces inflammation in the brain and amyloid beta buildup. Mice treated with the drug have shown improvements in their memory.
Researchers from Northwestern University have shown that NU-9, an experimental medication that the FDA has already approved for use in clinical trials for amyotrophic lateral sclerosis (ALS), has tremendous potential for treating Alzheimer’s disease. The small-molecule drug efficiently lowered toxic protein buildup in animal model brain cells, indicating that these neurodegenerative disorders have a common mechanism.
Misfolded protein buildup that affects brain function is a common characteristic of both Alzheimer’s and ALS. Unlike medications that target specific disease symptoms, NU-9 addresses the fundamental molecular pathways contributing to neurodegeneration. These results imply that NU-9 might work well for various neurodegenerative illnesses with similar pathogenic mechanisms.
According to Northwestern’s Richard B. Silverman, who developed NU-9, this drug is particularly unique because it works in several systems [1]. He stated human testing is necessary before they can determine how well it works to treat Alzheimer’s disease. However, the way upper motor neurons function in mice is similar to that of humans. Therefore, they think NU-9 should function.
Proceedings of the National Academy of Sciences published the study [2]. The research shows the drug’s efficacy in cellular cultures and a short animal study.
Common Mechanisms in Distinct Neurodegenerative Disorders
William Klein, a neurobiology professor at Weinberg and an Alzheimer’s disease expert, co-led the research team. They found that although ALS and Alzheimer’s disease involve distinct misfolded proteins, the fundamental mechanisms of cellular damage are identical.
He claimed their findings revealed that the same mechanism impacts two completely distinct proteins in two entirely different disorders. Cells in both disorders experience an accumulation of harmful proteins. There seems to be a common mechanism for protein removal and preventing them from aggregating. NU-9 rescues the cell-saving pathway.
Misfolded proteins build up inside brain cells in neurodegenerative illnesses, leading to toxicity that impairs regular brain function and ultimately results in cell death. Misfolded amyloid beta oligomers are a hallmark of Alzheimer’s disease, whereas misfolded SOD1 proteins are associated with ALS.
“These are good proteins gone bad,” Klein said. Although they are good proteins, they contribute to their own accumulation when they cluster together. They adhere to synapses, neighboring cells, and cells themselves. In the end, that results in brain cell loss and dysfunction.
Positive Outcomes in Animal and Laboratory Studies
The study team experimented with both cellular cultures and mouse models. They discovered that administering NU-9 to neurons before amyloid beta addition decreased protein accumulation inside cells and along dendrites in cell cultures. Interestingly, the protective effect remained even after the removal of NU-9 from the treated cells.
When given orally to mice with Alzheimer’s, NU-9 enhanced the mice’s memory performance. Additionally, follow-up research showed that the medication decreased Alzheimer’s disease-related brain inflammation.
Klein reported that NU-9 therapy effectively prevented or decreased brain inflammation. It prevents the development of amyloid beta oligomers and inhibits the effects of neuroinflammation, which cause significant brain damage. Thus, the medication is highly successful on both a cellular and an animal level.
Understanding the Mechanism of Action of NU-9
Although the exact mechanism of NU-9 is still under investigation, researchers have made substantial findings about its function. They discovered that NU-9 specifically inhibits the development of amyloid beta oligomers within cells but has no effect on protein creation outside of cells.
Subsequent investigation showed that the drug’s efficacy depends on the enzyme cathepsin B and lysosomes, one of the cell’s primary recycling centers. Alzheimer’s disrupts the recycling system and leads to the accumulation of amyloid beta. Amyloid beta proteins are reportedly transported into the lysosomes by NU-9, where cathepsin B breaks down the protein clumps.
Silverman explained that the proteasome and lysosome in a cell are two crucial ‘junk compartments’. They collect junk and other unneeded components and break them down for disposal. The team discovered that the proteasome has no role at all. The lysosome plays a part in how NU-9 functions. However, they are still attempting to determine precisely what NU-9 binds to in order to trigger the lysosome.
“It’s a black box phenomenon,” Klein continued. The movement of these harmful protein clusters across the cell resembles a relay race. The proteins are gathered in one vesicle, then another, and finally delivered to the lysosomes. Although the researchers are unsure about the precise target, they believe NU-9 aims for something during the early stages of that relay.
Significance for Future Treatments
Silverman, who also created pregabalin (Lyrica) to treat epilepsy, fibromyalgia, and nerve pain, has established Akava Therapeutics to market NU-9. Klein is a cofounder of Acumen Pharmaceuticals, a company presently undergoing clinical trials for a therapeutic monoclonal antibody for Alzheimer’s disease.
Researchers intend to investigate the efficacy of NU-9 in treating other neurological disorders, such as Huntington’s disease and Parkinson’s disease. They are also focusing on refining the compound to improve its effectiveness.
According to Silverman, the results imply that there may be common pathways among the neurodegenerative diseases, which were previously believed to be entirely distinct illnesses. This finding paves the way for a novel class of medicinal substances that, like NU-9, may be able to arrest several degenerative disorders before significant cell damage occurs.
Despite the encouraging results, the researchers stress that more thorough testing is required before Alzheimer’s disease human trials can start.
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References
- Morris, A. ALS drug effectively treats Alzheimer’s disease in new animal study. Northwestern Now. https://news.northwestern.edu/stories/2025/04/als-drug-effectively-treats-alzheimers-disease-in-new-animal-study/. Published Online: 8th April, 2025. Accessed: 14th May, 2025.
- Johnson, E.A., Nowar, R., Viola, K.L., Huang, W., Zhou, S., Bicca, M.A., Zhu, W., Kranz, D.L., Klein, W.L. and Silverman, R.B., 2025. Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases. Proceedings of the National Academy of Sciences, 122(10), p.e2402117122.
- ALS Drug NU-9 Shows Promising Results for Alzheimer’s Disease in Animal Study. MedPath. https://trial.medpath.com/news/2f802e85c1a57974/als-drug-nu-9-shows-promising-results-for-alzheimer-s-disease-in-animal-study. Published Online: April, 2025. Accessed: 14th May, 2025.
- Experimental Drug Effectively Treats Alzheimer’s in Preclinical Study. SciTechDaily. https://scitechdaily.com/experimental-drug-effectively-treats-alzheimers-in-preclinical-study/. Published Online: 16th April, 2025. Accessed: 14th May, 2025.
- ALS drug effectively treats Alzheimer’s disease in new animal study. Science Daily. https://www.sciencedaily.com/releases/2025/04/250408121324.htm. Published Online: 8th April, 2025. Accessed: 14th May, 2025.
