Nanogel Turns Brain Support Cells Into Neurons in Alzheimer’s Models

A nanoparticle-based treatment has converted support cells into neurons in laboratory models of Alzheimer’s disease, according to research published August 26 in Cell Biomaterials. The system, called Nano-ERASER, is a polymer nanogel designed to cross the blood-brain barrier and enter astrocytes. These star-shaped cells support the central nervous system. Once inside, the nanoparticles delivered antibodies targeting PTBP1, a protein the researchers sought to break down. Reducing PTBP1 prompted some astrocytes to change into neurons. The University of South Carolina researchers first tested the system on human astrocyte cultures and human brain organoids designed to mimic Alzheimer’s disease. In both settings, PTBP1 levels fell and astrocytes were converted into neurons. Additional testing indicated that the newly formed neurons were functional. The team then treated mice with Alzheimer’s disease using Nano-ERASER. Over a period of several weeks, the animals regained nesting abilities and performed better in a water-maze test, results the researchers interpreted as signs of improved learning and memory. Examination of the animals’ brains also showed greater neuron density, along with lower levels of neuroinflammation and amyloid-beta buildup. The researchers emphasize that the nanoparticles do not alter DNA. Their approach differs from gene-editing methods such as CRISPR, and the cell-reprogramming process is described as reversible. The study’s corresponding author, Peisheng Xu, said the team observed behavioral differences after a single injection and stronger effects after two injections. The findings address a disputed question in regenerative neuroscience: whether suppressing PTBP1 alone can produce new neurons inside a living brain. However, the study does not establish that Nano-ERASER can treat Alzheimer’s disease in people. The experiments were conducted in cell cultures, human organoids and mice, not human patients. The researchers plan to study the treatment’s longer-term effects, test it in nonhuman primates and potentially pursue human clinical trials. Those steps would be needed before its safety and effectiveness in people could be assessed.