The adult human brain has little ability to replace neurons lost in Alzheimer’s disease, the most common form of dementia. Current medicines can slow the illness but do not bring back lost thinking skills. In a paper published in Cell Biomaterials, researchers report that engineered nanoparticles can make new neurons in human brain organoids, and can also rebuild circuits and improve memory in mice.
The particles belong to a polymer nanogel system named Nano-ERASER, which carries antibodies. After crossing the blood-brain barrier, the particles entered astrocytes. Inside those cells the antibodies broke down a protein called PTBP1. With less PTBP1, astrocytes changed into neurons.
Unlike gene-editing tools such as CRISPR, Nano-ERASER does not rewrite DNA, and the cell change can in principle be reversed. The researchers said the aim is a method that may be both more effective and safer because it does not alter the genetic code.
Tests in dishes and in mice
The researchers first used Nano-ERASER on cultured human astrocytes and on human organoids built to resemble brains with Alzheimer’s disease. PTBP1 levels fell, astrocytes became neurons, and further tests showed those new neurons could function. Xu said the new neurons can mature and survive.
Mice with Alzheimer’s disease then received the treatment by injection. Over several weeks they nested more normally and finished a water maze more efficiently, signs of better learning and memory. Their brains also showed a higher density of neurons, less neuroinflammation—harmful immune activity in nervous tissue—and less buildup of amyloid-beta, a sticky protein fragment that is a hallmark of Alzheimer’s disease. Behavior already differed after one injection and improved further after two.
The work does not show that Nano-ERASER treats Alzheimer’s disease in people. It does add evidence on a disputed point: whether lowering PTBP1 alone can drive new neuron formation in a living brain. Next steps couldinclude longer follow-up, tests in nonhuman primates, and, later, human trials.