Alzheimer's hope: Nanoparticles regenerate cells to restore memory

A single injection of a nanoparticle treatment engineered to encourage the generation of new brain cells was enough to reverse cognitive decline in an animal model of Alzheimer’s disease.

Developed by researchers in the US, the remarkable new treatment could one day be used to treat patients in advanced stages of dementia by restoring the brain’s ability to recover from ongoing neurodegeneration.

“The new neurons can become mature and survive,” says senior author Peisheng Xu, a pharmaceutical researcher at the University of South Carolina.

“We also confirmed much higher neuron density in the brains of treated mice.”

Alzheimer’s disease is a battle between cell growth and the steady loss of neurons to inflammation. Because the brain can't quickly replace lost nerve cells in critical areas such as the hippocampus, people with the disease lose memory, cognition, and eventually the ability to feed or safely maintain balance.

Most approved treatments target mechanisms thought to cause inflammation, buying time by slowing neurodegeneration. Yet nothing can stop cell loss altogether. Nor can any current therapies repair or replace brain cells faster than they vanish.

A promising target for neural regeneration is a specialized, star-shaped cell called an astrocyte. Typically tasked with supporting and protecting neurons by providing energy and managing chemical fluctuations in the environment, these “nanny” cells can transform into “thinking” cells under the right circumstances.

Those circumstances face a major obstacle. Polypyrimidine tract-binding protein 1 (PTBP1) binds to RNA in astrocytes, preventing them from taking on nerve cell characteristics.

Based on past research, Xu’s team of researchers was confident that destroying PTBP1 would allow astrocytes and similar support cells to develop.

Unfortunately, some studies suggested it might not be quite so simple, with concerns that depleting the protein might not be enough to open the way. Then there is the whole question of precise delivery. There’s a world of difference between a living brain and a dish of cells, and PTBP1 does more than just prevent astrocytes from doing a nerve cell’s job.

That’s where nanoparticles come in. By combining a targeted protein-degradation system with a nanogel-based delivery, the team had successfully destroyed cancer cells in adult animals.

Called Nano-ERASER, the gel could safely transport PTBP1-specific antibodies across the blood-brain barrier. By attaching a system that could safely break down the proteins, the team found they could suppress its activity in the brains of adult mice with and without an Alzheimer’s disease model.

One of the most obvious signs of cognitive decline in mice is their ability to build a nest. Just as our habits of mind fail with age – whether it’s remembering how to make a cup of tea, or knowing the way home – mice with their own version of Alzheimer’s forget how to tidy up.

Within just a few weeks, injected mice with signs of neurodegeneration improved their nesting scores. They were also navigating mazes better, showing improved memory and spatial learning.

“After just two injections, these mice became smarter,” says the scientist. “Even after one injection, we already saw these mice’s behavior differ from that of the nontreated ones.”

While the experiment settles the question of whether PTB1 suppression can encourage neural regeneration on its own, its application in humans with Alzheimer’s disease is some way off.

Yet it is one more target researchers can focus on in their ongoing quest to improve the quality of life for individuals experiencing severe cognitive decline.

This research was published in Cell Biomaterials.

Source: Scimex