Unsung Heroes: Could Glial Cells Treat Huntington’s Disease?

New research is challenging how we think about treating brain diseases, like Huntington’s disease (HD). A study from the lab of Dr. Steven Goldman shows that transplanting healthy early-stage support cells from humans into the brains of adult mice that model HD improves movement, memory, and even survival. But that’s not all — these cells, called “glial progenitor cells”, seemed to influence neurons in the mouse brain to behave more like young, healthy ones. By targeting glia, rather than the neurons primarily affected by HD, this work opens the door to a bold new possibility for treating the disease.

The Brain’s Backstage Crew Steps Into the Spotlight

When we think about HD, we usually picture the effect the disease has on neurons. And for good reason: HD is a brutal genetic condition that primarily damages neurons, which are responsible for movement, learning, and memory. Historically, treatments in development have tried to target those neurons directly by trying to rescue them, replace them, or trying to silence the gene that’s wreaking havoc.

But what if the health of those same neurons could be improved by targeting other key players in the brain? In new work from the Goldman lab, scientists looked beyond neurons and focused instead on the brain’s supporting cast: glial cells. These “helper” cells, long thought to simply keep neurons fed and cushioned, are gaining notoriety as active architects of brain health. And when they’re replaced with healthy ones, they might be able to rebuild broken circuits and better support brain functions.

Huntington’s Disease 101: A Genetic Domino Effect

HD is caused by an expansion of a genetic sequence of CAG repeats in a gene called HTT. If just one copy of this faulty gene is inherited, that person will develop symptoms if they live long enough. The disease hits the striatum hard, an area of the brain in the center of the head responsible for movement and learning. In the striatum, HD leads to the death of medium spiny neurons (MSNs), the cell type that acts as the region’s main communication hubs.

As MSNs die off, so does a person’s ability to move smoothly, think clearly, and regulate their mood. Many past approaches trying to develop treatments for HD have largely focused on the neurons themselves. But neurons don’t live in a vacuum, and this new research shows that maybe we’ve been ignoring the soil while trying to rescue the tree.

The Aha Moment: Glia Aren’t Just Scenery

Earlier studies hinted at something big: when scientists transplanted healthy human glial progenitor cells into newborn HD mice, the disease slowed down. The mice behaved more like mice without the HD gene, their neurons fired less erratically, and their brain structures stayed more intact. That was enough to get scientists asking if this could work in adult mice too.

This new study aimed to find out. Researchers took human cells destined to become glia (called glial progenitor cells) and transplanted them into the striatum of young adult mice that model HD. These weren’t baby mice with developing brains, they were five-week-old mice already showing signs of decline.

But neurons don’t live in a vacuum, and this new research shows that maybe we’ve been ignoring the soil while trying to rescue the tree.

Rebuilding From the Inside Out

The results were impressive and encouraging.

The transplanted glia didn’t just survive, they appeared to thrive. They migrated throughout the striatum, integrated into the mouse brain, and replaced the host’s damaged glial cells. Crucially, they didn’t seem to develop the toxic protein clumps that plague HD cells.

Also striking were the effects on the mice themselves. In tests of movement, HD mice treated with these cells seemed to run around like their healthy peers. On tests of memory and anxiety-like behavior, they seemed to perform almost normally. And they lived about two weeks longer, which is significant for an animal model that usually dies by 18 weeks. While there’s no 1:1 comparison to what that could mean for people, or even that this approach will work for people, that’s a huge improvement in mouse time.

Glia as Gene Whisperers

Next the researchers dove into the neurons themselves to better understand the influence the non-HD glia could be having on them. They used a technique called single nucleus RNA sequencing (snRNA-seq), which shows what genes are turned on or off in individual cells. In untreated HD mice, the MSNs had dialed down levels of genes for communication, structure, and synapse-building.

But when those healthy glia were around, the neurons started singing a different tune.

Key genes flipped back on. Pathways that help neurons grow, connect, and function seemed to be revived. Even the way the DNA was packaged inside the cells appeared to shift toward a healthier state. It’s as if the glia were sending out repair signals, coaxing the neurons into reactivating their own genetic programs to regrow.

Brains Rewired, Literally

And the recovery wasn’t just molecular. The scientists also saw changes in brain structure.

Using a clever tracing method with a modified rabies virus, they imaged the neurons’ dendrites — the branch-like structures that receive signals from other neurons. In HD, these become shriveled over time, like a withered tree. But in the treated HD mice, the dendrites of MSN appeared to be restored, like a healthy tree with lots of branches. 

In other words, the addition of new glia led to healthier neuron structure, which seemed to lead to better function. It seems the glia weren’t just band-aids, they were blueprints for rebuilding.

What’s Next? And What’s the Catch?

Of course, there are caveats. These glial transplants were done in young adult mice before full-blown symptoms. Whether the same effects can be achieved in much older human brains with HD is still unclear. Also, the mouse model used here progresses very quickly, at rates much faster than the human disease, so further studies in slower models are crucial.

And while the researchers uncovered some of the key pathways involved in the neuron-glia dialogue, we still don’t fully understand how glia orchestrate this repair. Are they releasing molecules? Forming special contacts? Changing the local environment? The answers could point the way to new drugs, or even glia-based transplantation therapies in humans.

It’s as if the glia were sending out repair signals, coaxing the neurons into reactivating their own genetic programs to regrow.

The Takeaway: A New Chapter in Brain Repair

This study offers more than just hope for a new HD treatment, it shifts our perspective on how we might treat this brain disease. And if future studies show that these results hold in older brains with more advanced disease, they could represent a sea change in when we might be able to treat HD.

Glial cells, once considered the backstage crew of the brain, are stepping into the spotlight as active healers, architects, and perhaps even directors of recovery. If they can rewire HD brains, might they be able to do the same in Alzheimer’s, Parkinson’s, or ALS?

We’re just beginning to understand the choreography between glia and neurons. But this research is a clear sign that to truly heal the brain, we need to stop looking at neurons in isolation and start thinking about the whole ensemble.

TL;DR: Glia Are the Brain’s Hidden Powerhouses

• Huntington’s disease damages neurons, but neurons don’t work in isolation, they are supported by glial cells.
• A new study transplanted healthy human glial progenitor cells into adult HD mice.
• The results seemed to show improved movement, memory, and lifespan.
• The glia also seemed to have an impressive effect on neurons, appearing to allow them to reactivate a healthy genetic program to grow and function like healthy neurons.
• This suggests glial cells could be a powerful new therapeutic tool, not just for HD, but potentially for other neurodegenerative diseases too.

Learn More

Original research article, “Human glial progenitors transplanted into Huntington disease mice normalize neuronal gene expression, dendritic structure, and behavior” (open access).