In the world of neuroscience, where each breakthrough feels like one step forward and two steps back, a recent development out of Northwestern University is offering a rare and thrilling sense of progress. A small molecule drug known as NU-9—initially developed to combat amyotrophic lateral sclerosis (ALS)—has shown unexpected and remarkable promise in treating another formidable enemy: Alzheimer’s disease.
While it’s not yet time to proclaim victory over one of the most devastating neurological disorders, the results are undeniably exciting. NU-9 doesn’t merely alleviate symptoms—it targets the tangled roots of neurodegeneration itself. For the first time, scientists are watching a drug improve neuron health in Alzheimer’s disease by addressing the underlying biological mechanism, not just the visible effects.
“This drug is quite remarkable,” says Richard B. Silverman, the Northwestern chemist who invented NU-9. And in the world of Alzheimer’s research, “remarkable” is a rare and precious word.
Beyond Symptoms: The NU-9 Revolution
Traditional treatments for Alzheimer’s tend to focus on late-stage symptoms—memory loss, confusion, personality changes—without meaningfully altering the disease’s grim trajectory. NU-9 flips this paradigm on its head.
Rather than treating the symptoms associated with specific conditions like ALS or Alzheimer’s individually, NU-9 zeros in on the shared cellular mechanisms that fuel these diseases in the first place. This approach could represent a new era in neurodegenerative therapy—where one treatment targets the disease’s engine, not just its exhaust.
At the heart of many neurodegenerative conditions is a deceptively simple villain: misfolded proteins. Like a beautifully folded origami figure suddenly turned inside out, these proteins malfunction in structure and begin to accumulate where they shouldn’t—clogging cells, disrupting function, and eventually triggering cell death.
In ALS, it’s misfolded SOD1 proteins. In Alzheimer’s, amyloid beta oligomers. Both are “good proteins gone bad,” explains William Klein, co-lead author of the study and a professor of neurobiology at Northwestern. “They play a role in their own destruction. They stick to brain cells and synapses, and that disrupts function.”
But here’s the twist: NU-9 seems to intervene early in this self-destructive cycle, helping cells clear away the accumulating waste before it becomes deadly.
How It Works: Cleaning the Brain from the Inside
In their recent study, published March 3 in the Proceedings of the National Academy of Sciences, researchers tested NU-9’s effects on both cultured neurons and animal models. When amyloid beta was added to healthy neurons in the lab, the toxic oligomers quickly began to accumulate inside and around the cells. However, when the neurons were pre-treated with NU-9, something extraordinary happened—the protein buildup was dramatically reduced.
Even more impressive? The protective effects lingered long after NU-9 was removed from the cells. “It was like the neurons had been ‘trained’ to protect themselves,” says Klein.
But this wasn’t just a petri dish phenomenon. The team then administered NU-9 orally to mice genetically engineered to model Alzheimer’s disease. The result: a measurable improvement in cognitive performance. The treated mice performed better on memory tests, and postmortem brain analysis showed reduced inflammation—a key marker of Alzheimer’s progression.
“In addition to halting the toxic protein buildup, NU-9 tamped down inflammation in the brain,” Klein notes. “That’s a double win—it’s working both at the molecular level and at the system level.”
Cracking the Code: What NU-9 Actually Does Inside the Cell
What makes NU-9 so special? The short answer is: we don’t fully know yet. But researchers have some intriguing clues.
Inside every cell is a network of tiny recycling centers—lysosomes and proteasomes—responsible for breaking down waste, damaged proteins, and cellular debris. When this recycling system breaks down, misfolded proteins pile up and chaos ensues.
Silverman’s team discovered that NU-9 works specifically through the lysosomal pathway. It doesn’t touch the proteasome, suggesting the drug is fine-tuning one particular avenue of cellular cleanup.
Even more specifically, the drug seems to assist in directing harmful protein clumps into lysosomes, where an enzyme called cathepsin B can break them down. It’s like redirecting all the city’s trash trucks to take their loads to the right landfill.
But the process is complicated, and much remains to be understood. “It’s like a relay race,” says Klein. “These toxic proteins are passed from one vesicle to another until they reach the lysosome. NU-9 seems to help that hand-off happen more smoothly, but we’re still working out where exactly it acts in the sequence.”
One Molecule, Many Diseases?
The most compelling aspect of NU-9’s success may not be what it does for Alzheimer’s alone, but what it suggests about all neurodegenerative diseases. If misfolded proteins and disrupted lysosomal function are common threads, NU-9 and its chemical cousins might serve as a universal needle.
“It has long been assumed that ALS, Alzheimer’s, Parkinson’s, and Huntington’s are completely distinct diseases,” says Silverman. “But this suggests otherwise. If they share underlying mechanisms, then we might be able to develop treatments that work across multiple conditions.”
It’s a seismic shift in thinking: not one disease, but a family of disorders with overlapping biology. NU-9 could be the first in a new generation of broad-spectrum neuroprotective drugs.
From Lab to Clinic: The Road Ahead
NU-9 is no stranger to high expectations. It’s already been approved by the U.S. Food and Drug Administration (FDA) for clinical trials in ALS patients. Now, the Northwestern team is eager to pursue trials targeting Alzheimer’s and perhaps even Parkinson’s disease. But don’t expect overnight miracles.
“There’s still a long road ahead,” Klein cautions. More extensive animal studies, rigorous cognitive testing, and ultimately human trials will be needed before NU-9 becomes a household name in Alzheimer’s treatment.
Silverman is also working to refine the drug, enhancing its efficacy and exploring ways to optimize its delivery. The ultimate goal? A safe, effective, and widely accessible drug that doesn’t just manage neurodegeneration—it prevents or even reverses it.
And for patients and families facing the slow, relentless unraveling of diseases like Alzheimer’s, that hope is everything.
A Legacy of Innovation
Richard B. Silverman is no newcomer to life-changing medications. He’s best known as the inventor of pregabalin, better known by its brand name Lyrica, which is used to treat epilepsy, fibromyalgia, and nerve pain. With NU-9, he’s once again pushing the boundaries of what’s possible in medicinal chemistry.
Alongside him, William Klein brings decades of Alzheimer’s research to bear. His prior work with therapeutic antibodies laid groundwork for monoclonal antibody treatments now in clinical trials. Together, their collaboration represents the kind of synergy that fuels major scientific breakthroughs.
As founders of two biotech startups—Akava Therapeutics and Acumen Pharmaceuticals—they’re not just theorizing in a lab. They’re actively working to bring NU-9 from bench to bedside.
Looking Forward
What if a single drug could stop ALS in its tracks, clear out Alzheimer’s plaques, reduce inflammation, and potentially slow down Parkinson’s? That’s the tantalizing question NU-9 has placed before the scientific world.
Of course, there’s still work to be done. But for now, this tiny molecule is making big waves. And in the quiet corridors of neuroscience labs, the spark of something game-changing is alive and well.
One drug. Multiple diseases. A unifying theory of neurodegeneration. That’s not just remarkable—it’s revolutionary.
Reference: Elizabeth A. Johnson et al, 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 (2025). DOI: 10.1073/pnas.2402117122