A groundbreaking nanotherapy developed at Northwestern University traps toxic proteins before they destroy neurons—offering new hope in the fight against Alzheimer’s and ALS.
Key Points at a Glance
- New sugar-coated nanofibers trap misfolded proteins before they form toxic aggregates.
- Therapy significantly improves survival of human neurons exposed to Alzheimer’s proteins.
- Unstable nanofibers are more reactive, bonding with and neutralizing amyloid-beta proteins.
- Nanomaterial degrades safely into lipids, amino acids, and sugars with minimal side effects.
- Approach could complement existing therapies to target early-stage neurodegeneration.
What if the secret to halting Alzheimer’s disease was not in blocking toxic proteins after they’ve formed—but in catching them before they wreak havoc on the brain? That’s exactly what researchers at Northwestern University have achieved with a bold new nanotherapy designed to trap disease-causing proteins at their most vulnerable stage.
In a study published in the Journal of the American Chemical Society, scientists unveiled a sugar-coated nanomaterial that effectively “vacuum cleans” the brain’s biochemical environment, neutralizing misfolded proteins that would otherwise clump, invade neurons, and trigger neurodegeneration.
“We’ve created a system that targets the root cause of these devastating diseases before irreversible damage is done,” said Samuel I. Stupp, senior author of the study and director of the Center for Regenerative Nanomedicine at Northwestern.
In Alzheimer’s and ALS, proteins like amyloid-beta lose their normal shape and form sticky fibers that burrow into brain cells, eventually killing them. The new therapy halts that destructive process by trapping these misfolded proteins early—before they become lethal.
At the heart of the innovation is a class of materials known as peptide amphiphiles, molecules designed to self-assemble into nanofibers in water. Already used in existing drugs like Ozempic, peptide amphiphiles are known for their compatibility with the body. To this foundation, the Northwestern team added a natural sugar—trehalose—known for protecting proteins in plants and insects.
Once mixed with water, the molecules spontaneously formed nanofibers coated in trehalose. Counterintuitively, the sugar made the fibers less stable—which turned out to be the key to their effectiveness. The less stable the nanofiber, the more chemically reactive it became. And that instability made it eager to bond with rogue proteins.
Rather than ignore the surrounding chaos, the unstable fibers acted like a biochemical search party—hunting down the most dangerous proteins, binding to them, and locking them into harmless structures. “It’s like a clean-up crew that traps the toxic players before they become destructive,” said Stupp.
These trapped proteins no longer form toxic aggregates or penetrate neurons. Instead, they become part of a hybrid fiber, a new molecular structure that safely neutralizes the threat.
When tested on human neurons derived from stem cells, the nanotherapy produced remarkable results. Neurons exposed to amyloid-beta proteins and treated with the nanofibers showed significantly higher survival rates than untreated cells.
“The survival of motor and cortical neurons improved dramatically,” said Zijun Gao, first author and Ph.D. candidate in Stupp’s lab. “This suggests strong potential not only for Alzheimer’s but also for other neurodegenerative diseases like ALS.”
Importantly, the nanofiber materials degrade into benign compounds—lipids, amino acids, and sugars—posing minimal side effects. That makes them ideal candidates for therapeutic use in the brain’s sensitive environment.
While current Alzheimer’s treatments largely focus on later stages, where symptoms have already taken hold, this strategy targets the disease before it strikes. “Our therapy is ideally suited for early intervention,” said Stupp. “But because early diagnosis remains a challenge, it could also work as part of a combination therapy—joining forces with drugs that address later stages.”
The study, selected as an ACS Editors’ Choice, highlights the power of regenerative nanomedicine to transform how we approach complex neurological disorders. Rather than merely slow symptoms, this approach seeks to rewrite the early chapters of disease progression—before memory fades, before neurons die.
Supported by institutions including the NIH, the Spanish Ministry of Science, and the EU’s NextGenerationEU initiative, the research represents a milestone in neurodegenerative disease therapy and a beacon of hope for the millions affected worldwide.
Source: Northwestern University
