Scientists at Northwestern University have introduced a novel therapy aimed at addressing neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis (ALS). This new approach focuses on preventing the misfolding and aggregation of proteins, which are common issues in these conditions.
In neurodegenerative diseases, proteins tend to misfold and cluster around brain cells, leading to cell death. The innovative treatment developed by the researchers traps these proteins before they can form toxic structures that penetrate neurons. Once trapped, the proteins degrade harmlessly within the body.
The study was published in the Journal of the American Chemical Society and was selected as an ACS Editors’ Choice article. Samuel I. Stupp, a senior author from Northwestern, emphasized the potential of molecularly engineered nanomaterials to tackle the root causes of neurodegenerative diseases. "By trapping the misfolded proteins, our treatment inhibits the formation of those fibers at an early stage," he stated.
Stupp holds multiple positions at Northwestern University and is also the founding director of the Center for Regenerative Nanomedicine (CRN). Zijun Gao, a Ph.D. candidate in Stupp’s laboratory, is credited as the paper's first author. Zaida Alvarez from the Institute for Bioengineering of Catalonia led testing in human neurons.
According to WHO estimates, up to 50 million people worldwide may suffer from neurodegenerative disorders characterized by protein accumulation in the brain. Current treatments offer limited relief, highlighting a need for new therapies.
The research team used peptide amphiphiles with modified amino acid chains to develop their solution. These molecules self-assemble into nanofibers coated with trehalose—a natural sugar known for its protective properties against environmental stressors like dehydration and freezing.
When added to water, these peptide amphiphiles formed less stable nanofibers that were more reactive and likely to interact with toxic proteins such as amyloid-beta—an Alzheimer's-related protein. The nanofibers bonded with amyloid-beta proteins, effectively trapping them into stable filaments that could no longer harm neurons.
"This is a novel mechanism to tackle progression of neurodegenerative diseases," said Stupp regarding this innovative approach. Laboratory tests showed that trehalose-coated nanofibers improved neuron survival when exposed to toxic amyloid-beta protein.
Stupp suggests that combining this therapy with other treatments might enhance its effectiveness in targeting early-stage disease symptoms while complementing therapies for later-stage symptoms.
The study received support from several institutions including CRN, Chemistry of Life Processes Institute, Spanish Ministry of Science, National Institute on Aging of NIH and European Union’s NextGenerationEU initiative.