Tooth fairy therapy? Stem cells from teeth tested in a small Huntington’s disease trial

A small study from Brazil tested whether stem cells from human dental pulp, the soft tissue inside teeth, could help people with Huntington’s disease (HD). The results hint at small improvements on some movement measures, but the study had few participants who were tracked over a short timeframe, and many questions remain that raise red flags.

The allure of stem cells

Stem cells have long captured the imagination of scientists and families affected by neurodegenerative diseases. These versatile cells can divide and transform into different cell types, offering the hopeful possibility that they could repair or replace damaged brain tissue.

Stem cell treatments have been successful for other diseases, like spinal cord injuries and immunodeficiency diseases. They’re also emerging as treatments for some degenerative conditions, like macular degeneration, where vision is lost because cells in the retina die.

In HD, where neurons gradually die over decades, stem cells offer an appealing vision. But so far, they haven’t delivered on that promise and no stem cell–based therapy has proven to slow or stop HD progression.

Stem cells can be derived from a variety of sources. Embryonic stem cells come from embryos (perhaps unsurprisingly). Adult stem cells are more tissue specific and are found in the brain, bone marrow, or gut. And pluripotent stem cells can be created in the lab from skin cells or blood.

What have teeth got to do with HD?

The new twist in this latest study from Brazil is where the stem cells come from. Researchers used human dental pulp stem cells, collected from the soft tissue inside teeth, to create an experimental therapy called NestaCell. These cells are thought to perhaps support neurons and reduce inflammation.

Could stem cells from our teeth really help protect the brain in HD? The team hoped to answer that question by studying intravenous infusions of stem cells.

The study in a nutshell

The researchers, led by Dr. Joyce Macedo Sanches Fernandes and colleagues, ran a Phase II randomized, double-blind, placebo-controlled trial, the gold standard for testing a new therapy. 

People with HD were enrolled and randomly assigning them to one of three groups:

• Low dose: 1 million cells per kilogram of body weight, 13 participants
• High dose: 2 million cells per kilogram of body weight, 12 participants
• Placebo: an inactive infusion, 7 participants

Participants received nine intravenous infusions over 11 months. The main outcome for determining success of the trial was the Unified HD Rating Scale (UHDRS) Total Motor Score (TMS), a measure of movement problems. Other measures included Total Functional Capacity (TFC) (daily living skills), Total Chorea Score (involuntary movements), and MRI scans to track changes in brain structure.

What did they find?

Safe and well tolerated

First, the good news: NestaCell appeared safe. No serious side effects were linked to the treatment, and the overall rate of mild side effects was similar across groups. That’s an encouraging first step for any new therapy.

Hints of benefit

The researchers also reported some improvements in HD symptoms. Both treated groups showed better scores on the UHDRS-TMS (movement) than placebo. The higher-dose group also improved in functional capacity, suggesting possible benefit in daily life activities.

MRI scans hinted at slower brain tissue loss in treated patients, though these differences weren’t statistically significant, meaning they could be due to chance.

So the treatment seemed safe, and some numbers moved in the right direction. That’s intriguing, but not enough to be sure of real clinical benefit.

Why we should be cautious

As tempting as it is to get excited, there are several big reasons to view these results with caution.

1. Small study and short follow-up

With just 32 people who completed the trial who were divided among three groups, this was a small trial. Each group included roughly a dozen people, so a few participants doing unusually well (or poorly) could shift the averages. 

And the study lasted less than a year, almost certainly too short to know if any benefit would persist in a disease that changes slowly over decades. It’s also a limited timeframe in which to measure longer-term negative effects that could arise, like tumors, which are normally tracked in stem cell studies. 

So the treatment seemed safe, and some numbers moved in the right direction. That’s intriguing, but not enough to be sure of real clinical benefit.

2. No clear mechanism

It’s also unclear how injecting this type of stem cell might be helping. The researchers suggest these cells secrete helpful factors that reach the brain, but in reality, stem cells injected into the bloodstream are normally quickly filtered out. There’s no solid evidence that these cells can cross the blood-brain barrier or directly influence specific drivers of HD. In other words, there’s no convincing biological explanation for why this should work.

The researchers also mention findings from their own preclinical work in mice that these injected dental stem cells rarely reach the brain. The cells first go to the lungs before making their way to the rest of the body, with only about 2% ending up in the brain. Additionally, their other studies seem to show that the cells don’t “engraft” long-term, meaning they don’t take up permanent residence in the mice. While this is good for avoiding the creation of tumors (always a major concern for stem cell studies), it also means they may not stick around and perform positive functions either.

3. Selective improvements

Only some measures improved, and there was no clear dose-response pattern (higher doses didn’t clearly lead to better results). The MRI “trend” wasn’t statistically significant. When a few outcomes show changes but others don’t, and when the effects are small, there’s a real risk that the apparent benefits are due to random chance rather than the treatment itself.

Stem cells and HD: a long, bumpy road

Stem cell therapies for HD have been studied for decades, from foetal cell transplants in the 1990s to bone marrow-derived mesenchymal stem cells more recently. Despite repeated efforts, none have convincingly slowed or reversed HD progression in controlled trials.

Why? It turns out that the brain’s complex wiring is extremely hard to rebuild. Injected stem cells don’t easily integrate into neural networks and simply putting them in the body, especially via the bloodstream, doesn’t guarantee they’ll reach or repair the brain. NestaCell adds an interesting new chapter to this story, but it doesn’t fundamentally change the underlying challenges.

Other groups are exploring brain-repair strategies grounded in clearer biology. Recent work suggests that it may be possible to coax the adult brain into regenerating the specific neurons lost in HD, potentially restoring circuitry rather than just supporting it. In parallel, scientists are developing techniques to reprogram glial support cells into new, functional neurons, offering a more targeted “replace what’s lost” approach. These early-stage efforts are still far from the clinic, but they point to a future of regeneration therapies that rest on more solid science.

Hope, hype, and healthy scepticism

Stem cell studies often generate excitement, and headlines, because the idea of “regenerating” the brain is so compelling. But for the HD community, it’s crucial to distinguish scientific hope from premature hype.

NestaCell adds an interesting new chapter to this story, but it doesn’t fundamentally change the underlying challenges.

While this study’s results are interesting, they don’t provide strong evidence that dental pulp stem cells can alter HD progression. Larger, longer, and independently run trials will be needed before anyone can claim this is a real treatment.

Families should also be wary of unregulated stem cell clinics, which are up and running across the world and sometimes use early academic studies like this to advertise costly, unproven therapies. Until treatments are tested rigorously and approved by regulators, they should be considered experimental.

What happens next?

The authors suggest that NestaCell should move on to a larger Phase III trial to confirm efficacy and safety in a bigger group of patients. That’s an ambitious next step, and one that will require careful justification, especially given the lack of a clear mechanism and the modest nature of the results.

In the meantime, the HD research community can view this as a creative, if unconventional, attempt to explore new ideas. It’s a reminder that science advances by testing even unlikely hypotheses, but that strong evidence, not wishful thinking, is what ultimately drives progress.

Summary

• Stem cells derived from human dental pulp (from teeth), delivered by IV infusion
• 32 people with HD participated in a small Phase II randomized trial to test this therapy
• The treatment appeared safe and results suggest small improvements on some measures for signs and symptoms of HD, but no clear or consistent benefits
• This study contributes to our understanding of stem cell therapies in HD, but this drug is not ready for clinical use as the results are preliminary and biologically unclear
• Larger, independent studies are needed before anyone should consider “tooth stem cells” a real therapy for HD.

Learn more

Fernandes JMS et al. Stem Cell Research & Therapy (2025). “Phase II trial of intravenous human dental pulp stem cell therapy for Huntington’s disease: a randomized, double-blind, placebo-controlled study.” https://doi.org/10.1186/s13287-025-04557-2