Tooth fairy therapy? Stem cells from teeth tested in a small Huntington’s disease trial
A trial tested stem cells from human teeth as a possible treatment for HD. The approach appeared safe with some improvements in symptoms, but the small size of the study and the unclear underlying science of this approach means caution is urged.
A small study from Brazil tested whether stem cellsstem cells Cells that can divide into cells of different types 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 cellsstem cells Cells that can divide into cells of different types
Stem cellsstem cells Cells that can divide into cells of different types have long captured the imagination of scientists and families affected by neurodegenerativeneurodegenerative A disease caused by progressive malfunctioning and death of brain cells (neurons) 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 neuronsneuron Brain cells that store and transmit information gradually die over decades, stem cellsstem cells Cells that can divide into cells of different types 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 cellsstem cells Cells that can divide into cells of different types can be derived from a variety of sources. Embryonic stem cellsstem cells Cells that can divide into cells of different types come from embryosembryo the earliest stage during the development of a baby, when it consists of just a few cells (perhaps unsurprisingly). Adult stem cellsstem cells Cells that can divide into cells of different types are more tissue specific and are found in the brain, bone marrowbone marrow The gooey stuff in the middle of bones, that manufactures blood cells. When eaten, gives dogs a healthy coat and vitality, or gut. And pluripotent stem cellsstem cells Cells that can divide into cells of different types 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 cellsstem cells Cells that can divide into cells of different types come from. Researchers used human dental pulp stem cellsstem cells Cells that can divide into cells of different types, collected from the soft tissue inside teeth, to create an experimental therapy called NestaCell. These cells are thought to perhaps support neuronsneuron Brain cells that store and transmit information and reduce inflammationinflammation Activation of the immune system, thought to be involved in the HD disease process.
Could stem cellsstem cells Cells that can divide into cells of different types from our teeth really help protect the brain in HD? The team hoped to answer that question by studying intravenous infusions of stem cellsstem cells Cells that can divide into cells of different types.
The study in a nutshell
The researchers, led by Dr. Joyce Macedo Sanches Fernandes and colleagues, ran a Phase II randomized, double-blind, placeboplacebo A placebo is a dummy medicine containing no active ingredients. The placebo effect is a psychological effect that causes people to feel better even if they’re taking a pill that doesn’t work.-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
- Placeboplacebo A placebo is a dummy medicine containing no active ingredients. The placebo effect is a psychological effect that causes people to feel better even if they’re taking a pill that doesn’t work.: 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 (UHDRSUHDRS A standardized neurological examination that aims to provide a uniform assessment of the clinical features of HD) Total Motor Score (TMS), a measure of movement problems. Other measures included Total Functional CapacityTotal Functional Capacity A standardized rating scale for function in HD, used to assess capacity to work, handle finances, perform domestic chores and self-care tasks (TFCTotal Functional Capacity A standardized rating scale for function in HD, used to assess capacity to work, handle finances, perform domestic chores and self-care tasks) (daily living skills), Total Choreachorea Involuntary, irregular ‘fidgety’ movements that are common in HD Score (involuntary movements), and MRImagnetic resonance A technique using powerful magnetic fields to produce detailed images of the brain in living humans and animals 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 UHDRSUHDRS A standardized neurological examination that aims to provide a uniform assessment of the clinical features of HD-TMS (movement) than placeboplacebo A placebo is a dummy medicine containing no active ingredients. The placebo effect is a psychological effect that causes people to feel better even if they’re taking a pill that doesn’t work.. The higher-dose group also improved in functional capacity, suggesting possible benefit in daily life activities.
MRImagnetic resonance A technique using powerful magnetic fields to produce detailed images of the brain in living humans and animals scans hinted at slower brain tissue loss in treated patients, though these differences weren’t statistically significantstatistically significant Unlikely to have arisen by chance, according to a statistical test, 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 cellsstem cells Cells that can divide into cells of different types injected into the bloodstream are normally quickly filtered out. There’s no solid evidence that these cells can cross the blood-brain barrierblood-brain barrier A natural barrier, made from reinforcements to blood vessels, that prevents many chemicals from getting into the brain from the bloodstream 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 cellsstem cells Cells that can divide into cells of different types 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 MRImagnetic resonance A technique using powerful magnetic fields to produce detailed images of the brain in living humans and animals “trend” wasn’t statistically significantstatistically significant Unlikely to have arisen by chance, according to a statistical test. 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 cellsstem cells Cells that can divide into cells of different types 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 marrowbone marrow The gooey stuff in the middle of bones, that manufactures blood cells. When eaten, gives dogs a healthy coat and vitality-derived mesenchymal stem cellsstem cells Cells that can divide into cells of different types 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 cellsstem cells Cells that can divide into cells of different types 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 neuronsneuron Brain cells that store and transmit information 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 neuronsneuron Brain cells that store and transmit information, 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 cellsstem cells Cells that can divide into cells of different types 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 IIIphase III The phase in the development of a new treatment where clinical trials are conducted using many patients, to determine whether the treatment is effective trial to confirm efficacyefficacy A measure of whether a treatment works or not 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 cellsstem cells Cells that can divide into cells of different types 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 cellsstem cells Cells that can divide into cells of different types” a real therapy for HD.
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