Nanoparticles developed in the lab could contribute to regenerating brain cells and to the recovery of some cognitive abilities affected by Alzheimer’s disease, according to a new study conducted in mice and human brain models.
The investigation, published in the journal Cell Biomaterials, from Cell Press, tested a nanoparticle system named Nano-ERASER, developed by an international team led by researchers from the University of South Carolina. The results point to the capability of this technology to cross the blood-brain barrier, reach certain brain cells, and induce the formation of new neurons.
The adult human brain has a limited capacity to repair or regenerate neurons lost due to Alzheimer’s disease, the most common form of dementia. Although available treatments can slow disease progression, they currently cannot reverse cognitive decline.
The Nano-ERASER uses a polymeric nanogel with antibodies designed to degrade specific proteins. After crossing the blood-brain barrier, the system enters astrocytes, star-shaped supporting cells that are abundant in the central nervous system.
Inside these cells, the nanogel uses antibodies to degrade a protein called PTBP1. This process triggers the conversion of astrocytes into neurons.
The researchers initially tested the technology in cultures of human astrocytes and in human brain organoids developed to reproduce some features of Alzheimer’s disease. In both models, reducing PTBP1 levels led to the conversion of astrocytes into neurons, with subsequent tests indicating that these new cells were functional.
Improvements observed in mice
The team then moved on to animal models of Alzheimer’s disease. Over several weeks, the treated mice recovered nest-building abilities and were able to complete a water maze more efficiently, results that the researchers associate with improvements in learning and memory.
The brains of treated animals also showed a higher density of neurons, accompanied by a reduction in neuroinflammation and the accumulation of beta-amyloid protein, one of the features associated with Alzheimer’s disease.
“The new neurons can mature and survive. We also confirmed a much higher density of neurons in the brains of the treated mice,” says Peisheng Xu, Professor of Pharmacy at the University of South Carolina and corresponding author of the study.
“Unlike genetic editing tools like CRISPR, Nano-ERASER does not directly alter DNA and the cellular reprogramming process is reversible.”
“We hope this could be more effective and also safer. We do not need to worry about potential genetic side effects,” Xu explains.
According to the researcher, behavioral effects were observed even after a small number of administrations. “After only two injections, these mice became smarter. Even after a single injection, we already observed differences in the behavior of these mice compared to those that had not been treated.”
Still far from a human application
Despite the results, the investigators emphasize that the study does not demonstrate that Nano-ERASER could treat Alzheimer’s disease in humans. The investigation represents a proof of concept in cellular models, organoids, and animals and further investigation will be needed before any potential clinical use.
The team now aims to evaluate the long-term efficacy of the platform, test the technology in non-human primates, and, in a later stage, study the possibility of advancing to clinical trials in humans.
“If we can bring it into clinical practice, we may have hope for patients with Alzheimer’s,” concludes Peisheng Xu.
