A recent article in the scientific journal, Nature describes “A natural experiment on the effect of herpes zoster (shingles) vaccination on dementia”. This study makes similar conclusions to other studies worldwide, and was based on a regulatory phenomenon in Wales, UK, in which depending on a precise birth date in 1933, people could receive a free herpes zoster (shingles) vaccine, or not, even with birthdays a week apart from each other. This led to two very distinct groups of people who were about the same age: almost all vaccinated versus almost none vaccinated. Then a simple question was asked…
Is there any difference in dementia incidence between these two groups of people?
The answer was a clear yes, by 20%, and the predominant effect was in women, a component that is not understood yet. Incredibly, this would make the shingles vaccine more effective at reducing Alzheimer’s disease incidence than any recent FDA-approved drug. But why? Does shingles cause Alzheimer’s? What about other common vaccines? Do they have any effect?
This question has been asked in so many studies worldwide, it’s best at this point to refer to analysis of many studies, or meta-analyses, which compare all the data on an even ground. The conclusion across many studies is similar: influenza, pneumonia, as well as tetanus, diphtheria, pertussis (dTAP) vaccines all reduce risk of developing Alzheimer’s and the more broadly defined dementia.
So, if it’s not any one virus, or bacteria, then how can so many different types of infection contribute to neurodegeneration? And how do vaccines reduce the risk of developing these brain diseases?
The use of vaccines and good hygiene habits are critical for reducing bacterial and viral infections. Research suggests committing to these practices could do more than prevent a few days of missed work and 2 weeks on the couch, and could actually lower the risk of developing dementia.
Vaccines can help even after infection
Chicken pox infections took place in most children prior to the common use of varicella vaccine in the late 90s. While people were told for decades that they cannot get the virus again, the reality is that their immune systems learned how to control the virus for the rest of their lives. The virus never goes away, and it remains dormant in the nervous system.
If there is a period of an immune compromising event, like illness, aging, or chemotherapy, people can see the zoster virus re-activate leading to the condition of shingles, which is painful because the virus is in sensory neurons and in skin. So the best advice for those infected once with chicken pox is to take the two dose vaccine later in life to prevent shingles by keeping the immune system primed to control the virus.
But is this relevant to HD?
These studies aren’t just about dementia. As well, there are observed lower incidences of Parkinson’s disease in those who were vaccinated. There has been a classic connection between influenza infections and onset of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, another progressive neurodegenerative disease with genetic origins that is often seen triggered by something called a “redox imbalance.”
A redox imbalance refers to high levels of toxic byproducts of cellular metabolism, called reactive oxygen species (ROS), reactive sulfur species (RSS), or reactive nitrogen species, that are essentially the pollution in cells as a result of burning energy. It’s in these toxic reactive byproducts that lies the clues to the efficacy of vaccines against neurodegeneration.
The response to infections, most infections, is inflammation, where the soldiers of the immune system can use potent blasts of ROS to wipe out bacteria and viruses. In the aftermath, in young, healthy people, the brain’s cellular powerhouse (the mitochondria) can clean up those reactive byproducts and allow recovery from inflammation.
However, two events can prevent this response to bacterial or viral invaders from happening in people: 1) an underlying genetic disease, such as HD, which is known to affect mitochondria, 2) and/or human ageing, as all humans lose mitochondrial efficiency with age. This impact on mitochondria lowers their ability to lower ROS.
In HD, particularly later in life, we have both situations, which makes inflammation, like that caused by infections, dangerous. It’s particularly a problem in the brain because brain cells are very active, burning a tremendous amount of energy, even at rest, and a byproduct of all that burning is ROS.
Toxic byproducts build up as a result of cellular metabolism, a process that can be compounded when someone has a bacterial or viral infection. Normally, this cellular pollution is cleared by mitochondria. But some diseases, like HD, impact the function of mitochondria, impacting their response to bacterial or viral invaders.
The take home message
While there is no vaccine that is claiming to prevent neurodegeneration, these correlations between vaccination and lower disease risk may be important. At this point, there are not published studies on the protective effect of vaccines in HD and this information is not yet captured in the ENROLL-HD study.
However, it is prudent to suggest that those with HD or those who are gene carriers avoid any viral or bacterial infections through the use of vaccines and good hygiene habits we were all reminded of during the onset of COVID-19.
Summary
Multiple vaccines (shingles, flu, pneumonia, dTAP) are associated with 20% reduced dementia risk, which data suggests is more effective than recent Alzheimer’s drugs
Effects are seen across Alzheimer’s, other dementias, and Parkinson’s disease
Infections trigger inflammation and produce toxic cellular byproducts (like reactive oxygen species) that healthy mitochondria normally clear
In HD, mitochondria are already impaired and struggle to handle inflammation from infections
Aging also reduces mitochondrial efficiency, creating double risk for people with HD later in life
Brain cells are especially vulnerable due to high energy use and resulting toxic byproduct production
Bottom line for HD community: Stay current on vaccines and practice good hygiene to avoid infections that could stress already-compromised mitochondria
Acknowledgments
We thank Dr. Dr. Caitlyn Mullarkey, Dr. Matthew Miller, and Dr. Dawn Bowdish from McMaster University in Toronto, Canada for their input on this article.
UniQure announced on January 9, 2026 that they have scheduled a Type A meeting with the FDA to discuss the approval pathway for AMT-130 in the United States. Type A meetings are urgent, high-priority discussions reserved for urgent issues, and they happen fast, typically within 30 days. The meeting will focus on determining exactly what data package the FDA would need to support accelerated approval. After two months of uncertainty following November’s regulatory setback, this represents a structured opportunity for both sides to hopefully find a path forward.
A Critical Next Step
Just over two months after the November regulatory setback that left many within the HD community confused and deflated, uniQure announced on January 9 that the FDA has scheduled a Type A meeting to discuss the path forward for AMT-130 in the US.
While the press release is brief, the meeting type itself tells us something important: this is urgent, and both sides have agreed to come together to try and find a path forward.
The Type A meeting is a way for uniQure and the FDA to check the map together on exactly how to get their potential treatment for Huntington’s disease from where we are now to where we want to be.
What Exactly Is a Type A Meeting?
In the world of FDA interactions, not all meetings are created equal. The FDA offers several types of formal meetings with drug developers, but Type A meetings occupy a special category. They’re reserved specifically for situations where a development program has stalled, like when there’s a clinical hold, major safety concerns, or formal dispute that need to be addressed before a drug can move forward.
Think of it like this: if regular FDA meetings are scheduled check-ins during a road trip, a Type A meeting is pulling over to consult the map when you’ve hit an unexpected detour. It signals both urgency and a genuine attempt to hopefully problem-solve rather than just exchange information.
While the uniQure press release didn’t include a date for this meeting, Type A meetings are scheduled within 30 calendar days of the FDA receiving the request. So we should have more information by early February.
Type A meetings happen much faster than the 60-75 days typical for other meeting types. This expedited timeline reflects their high-priority nature. The meeting package (all the supporting documents and specific questions) must be submitted at the same time as the meeting request, and the FDA aims to provide preliminary responses just two days before the scheduled meeting.
What Can Companies Gain from Type A Meetings?
Type A meetings serve several purposes. They can help:
Resolve disputes about trial design requirements or regulatory decisions
Lift clinical holds by determining what modifications or additional data are needed
Chart a path forward when a development program has stalled due to regulatory concerns
Clarify expectations so companies know exactly what the FDA requires
The meetings themselves are typically 60 minutes, focused and structured around a specific agenda agreed upon beforehand. Within 30 days after the meeting, the FDA issues formal meeting minutes summarizing key takeaways, agreed-upon actions, and next steps.
What UniQure Is Seeking
According to the press release, the meeting will focus on “the Biologics License Application (BLA) data package to support accelerated approval of AMT-130.” In other words: what exactly would the FDA need to see in order to grant approval through the accelerated pathway?
This is crucial. Back in November, uniQure learned that their Phase 1/2 data compared to external controls from the Enroll-HD database, which the FDA had previously indicated would be acceptable, was no longer deemed sufficient as the primary evidence for approval. The Type A meeting gives both parties a structured opportunity to discuss what would be sufficient.
CEO Matt Kapusta emphasized the urgency: “The Huntington’s disease community, including patients and clinicians, has emphasized the profound unmet medical need and the importance of timely access to potentially disease-modifying therapies such as AMT-130.”
By early February, we should have an idea of the next steps uniQure needs to take to continue to advance AMT-130 for the treatment of Huntington’s disease in the US. While we wait, it’s important to remember that regulatory discussions around AMT-130 continue to advance in the EU and UK.
What Happens Next
UniQure stated they will “provide a regulatory update after receipt of official meeting minutes from the scheduled Type A meeting.” Those minutes should arrive within 30 days of whenever the meeting occurs, which, given the expedited timeline, could be as soon as late January or early February 2026.
The meeting minutes will be critical. They’ll spell out exactly what the FDA believes would constitute adequate evidence for approval, whether that means additional trial data, a different statistical approach, or something else entirely. This clarity is what’s been missing since November.
The Bigger Picture
This announcement represents forward movement, though it’s critical to remember that it doesn’t guarantee a specific outcome. What it does confirm is that both uniQure and the FDA are actively working to find a path forward rather than simply walking away from AMT-130.
The data haven’t changed. AMT-130 still appears to show a slowing of disease progression with a manageable safety profile in the original analysis. What’s being negotiated is the regulatory framework: how to demonstrate that finding in a way that meets the FDA’s standards for approval.
For the HD community, which has signed over 46,000 petition signatures and issued a Statement of Unity from major advocacy organizations, this meeting represents a chance for their voices to be heard, not just in public forums but in the regulatory decisions that ultimately determine drug access.
Meanwhile, uniQure continues to advance regulatory discussions in the EU and UK, providing alternative pathways that could benefit the global HD community regardless of the US outcome.
The coming weeks will be telling. The outcome of the Type A meeting could provide the roadmap needed to bring AMT-130 to patients. Alternatively, it could clarify just how high the remaining hurdles are. Either way, the HD community will finally have more concrete answers than they’ve had since that disappointing November announcement.
Summary
UniQure announced a Type A meeting has been scheduled with the FDA to discuss AMT-130’s approval pathway
Type A meetings are high-priority, urgent discussions reserved for urgent issues on stalled development programs
The meeting will focus on determining what data package could potentially support accelerated approval
Type A meetings typically occur within 30 days and are designed to resolve critical regulatory roadblocks, so we should know more by early February
UniQure will provide an update after receiving official meeting minutes
Doctors have been prescribing drugs to help manage Huntington’s disease (HD) symptoms like chorea (involuntary movements) and irritability for decades. But surprisingly, there are not many studies directly comparing these medications head-to-head. A new study called Neuro-HD, published in Parkinsonism & Related Disorders, helps to fill this gap. Researchers compared three commonly used drugs over one year in people with HD: tetrabenazine, olanzapine, and tiapride. Their findings support a more personalised, symptom-by-symptom approach to treatment, and suggest that olanzapine may have advantages for some people.
Why was this study needed?
Tetrabenazine is a type of drug called a VMAT2 inhibitor, one of the only classes of drug that has clearly proven benefits for movement symptoms of HD in large placebo-controlled trials. In many countries VMAT2 inhibitors have been the “default” option for doctors to prescribe to people with HD. However, tetrabenazine can have negative side effects, like worsening mood and sleepiness. It’s also not designed to help with behavioural symptoms, like irritability.
Antipsychotic drugs (also known as neuroleptics) such as olanzapine and tiapride are widely used in HD, especially in Europe, but mostly based on clinician-patient interactions or clinician preference rather than strong trial data. These medications are typically prescribed to help manage symptoms including involuntary movements, irritability, aggression, anxiety, and psychosis, which can be distressing for both people with HD and their families.
There are not yet disease-modifying treatments for Huntington’s disease, but symptom-management medicines remain important tools that can improve quality of life for people with HD and their families.
Until now, no large randomized study had directly compared these treatments over a meaningful length of time. That’s where Neuro-HD comes in.
How was Neuro-HD designed?
Neuro-HD was a randomized clinical trial run across 11 centres in France that enrolled 179 adults with manifest HD who had a clinical reason to start or change an antipsychotic drug. Participants were randomly assigned to receive one of three treatments: olanzapine, tetrabenazine, or tiapride.
They were then followed for 52 weeks. Importantly, this was an open-label study, so everyone knew which drug they were taking, and doctors were allowed to adjust doses or switch medications if needed, reflecting real clinical practice.
One of the main outcomes the researchers looked into was a measure called the Independence Scale, which gives a readout of how much help a person needs in daily life. They also carefully tracked motor symptoms (including chorea), behavioural symptoms (like irritability and depression), thinking abilities, and side effects.
Did any drug slow disease progression?
In short: no. But nor did we expect these drugs to; these are symptom management drugs not disease-modifying drugs.
The Neuro-HD trial reinforces an important message: that HD can impact each person in a unique way and there is no single “best” drug for managing HD symptoms.
Over one year, all three groups showed a similar decline in independence that is expected with HD progression. None of the drugs slowed overall disease progression or preserved independence better than the others.
Effects on movement: who improved most?
Movement symptoms improved in all three groups, but the clearest benefits were seen with tetrabenazine and olanzapine. Both drugs led to significant reductions in some measures of movement changes in HD over one year, although not Total Motor Score (TMS), a commonly used metric to track HD symptom progression. Olanzapine also came with a trade-off: people taking it experienced a small but measurable increase in rigidity (stiffness).
Tiapride showed smaller and less consistent improvements.
Effects on irritability and behaviour
This is where the drugs really differed. Olanzapine significantly improved irritability and overall behavioural scores, which measure changes in irritability, depression, apathy, anxiety, obsessive behaviours, and psychosis.
Tiapride also helped irritability, but less strongly, while tetrabenazine did not improve irritability and was more often linked to mood problems, particularly depressive symptoms and sedation.
For families struggling with anger, impulsivity, or aggression, symptoms that can be incredibly distressing, this finding is especially relevant.
Side effects of these drugs
All three drugs caused side effects, but their profiles were different. Tetrabenazine was most often linked to, depression, suicidal thoughts as well as drowsiness and fatigue. These side effects led to more people stopping or switching treatment.
Huntington’s disease is not just one symptom, it can affect movement, mood, thinking, and behaviour in different ways for different people. Image credit: Creative Commons – Tara Winstead.
Meanwhile olanzapine was associated with weight gain and mild increases in cholesterol. These effects were usually manageable, and fewer people stopped olanzapine overall. Notably, far fewer people stopped olanzapine because of depression or suicidal thoughts, giving it a more favourable mood-related safety profile in this study
Tiapride sat somewhere in between, helping irritability but with fewer benefits for chorea.
What does this mean for people with HD?
The Neuro-HD trial reinforces an important message: that HD can impact each person in a unique way and there is no single “best” drug for managing HD symptoms. Instead it suggests that:
Tetrabenazine remains effective for chorea, but mood needs close monitoring.
Olanzapine may be a strong option when movement and behavioural symptoms, especially irritability, occur together.
Tiapride may help irritability, particularly in settings where it’s commonly used.
The results support individualised treatment, where doctors consider the full symptom picture (movement, mood, behaviour, sleep, and weight) rather than focusing on chorea alone.
Why this study matters
Large, long-term, head-to-head trials like Neuro-HD are important studies for the HD community. This study reflects real-world care, includes people with complex psychiatric histories, and provides practical evidence clinicians can use today.
For many people with HD, these medications remain a critical part of symptom management. They are commonly used to help manage challenging symptoms such as irritability, aggression, anxiety, or psychosis, and for some individuals they can make a meaningful difference to daily life and safety.
That said, it’s still fairly common for many people with HD to be prescribed certain medications simply because they have HD. But that approach can lead to unnecessary side effects without real benefit. Instead, this study suggests that treatments should be targeted to specific symptoms with a clear goal in mind. This way, clinicians can weigh the potential benefits against possible harms and make decisions that truly improve quality of life.
Decisions about starting, stopping, or changing these medications should always be made through open and honest conversations between people with HD, their families, and their clinical care teams. It can be harmful to suddenly stop these drugs or change how you take them without first talking to a clinician, and anyone experiencing side effects or new symptoms should speak with a clinician rather than making changes on their own
This study also highlights the need for future trials comparing other commonly prescribed drugs, such as risperidone, aripiprazole, or newer VMAT2 inhibitors like deutetrabenazine, using outcomes that matter to patients and families. For now, Neuro-HD offers something the HD community has long needed: clearer evidence to guide everyday treatment decisions.
Summary
Neuro-HD was a year-long, head-to-head clinical trial comparing three commonly prescribed Huntington’s disease medications—tetrabenazine, olanzapine, and tiapride—in 179 people with HD across France.
No drug slowed HD progression, but all three helped manage symptoms in different ways.
Tetrabenazine and olanzapine improved movement, while tiapride had smaller effects.
Olanzapine best improved irritability and behaviour, with fewer mood problems than tetrabenazine.
The takeaway: treatment should be personalised, based on each person’s mix of movement, mood, and behavioural symptoms
As of January 1, HDBuzz is officially out on its own! Cue your celebratory party poppers as we enter this new chapter with an excited (and nervous!) smile. After lots of preparation, planning, and behind-the-scenes work, HDBuzz has become an independent nonprofit organisation. This marks a major milestone for our team and for the global Huntington’s disease (HD) community we serve.
But independence doesn’t mean we did this alone. Quite the opposite. In this article we want to share what this transition means, express our deep gratitude to the Huntington’s Disease Foundation (HDF) for their fiscal sponsorship and all of our other financial supporters, and explain how you can help support HDBuzz as we take on new responsibilities in this next chapter.
Thank You to the Huntington’s Disease Foundation and our Sponsors
Since February 2024, HDBuzz has operated under the fiscal sponsorship of the Huntington’s Disease Foundation. This relationship made our work possible.
HDF provided essential infrastructure that allowed HDBuzz to exist and grow: financial oversight, legal and administrative support, and stability during periods of transition and expansion. And perhaps the largest benefit was that they allowed us to use their charitable status so that we could maintain 501c3 status while waiting for the IRS to process our paperwork. Fiscal sponsorship may sound dry, but in practice it meant that scientists could focus on writing, editing, translating, and explaining HD research, all while knowing the organisational foundations were solid.
We are so grateful for all of your support on this journey so far – thank you!
Just as importantly, HDF believed in the value of independent, plain-language science communication for HD families long before it was obvious or easy. That trust gave HDBuzz the space to grow into the resource it is today. For that, we are tremendously thankful.
We are also deeply grateful to our sponsors and supporters who helped sustain HDBuzz during this period, including charitable foundations, partner organisations, and, most importantly, the HD community itself. Every person who clicked the donate button, shared our work, or contributed what they could played a real role in getting HDBuzz to this moment. Thank you!
These individual donations, large and small, were not just financial support; they were a vote of confidence in the idea that the HD community deserves clear, unbiased, and accessible science. HDBuzz exists because readers believed it should.
We are profoundly grateful to HDF for their sponsorship, partnership, and confidence in our mission, and to every supporter who stood behind us along the way. Our independence is not a separation born of disagreement. It is the natural next step of something that was carefully nurtured.
Thank you, HDF, and thank you to the global HD community, for helping us get here.
Why Independence Matters
HDBuzz has one core purpose: to explain HD research and clinical trial news clearly, accurately, and without spin.
As the HD research landscape has grown more complex, with late-stage clinical trials, regulatory uncertainty, and increasing commercial involvement, independence and unbiased reporting has become more important than ever. Families need a trusted source that can explain both good news and bad news, without conflicts of interest and without pressure to soften uncomfortable truths.
HDBuzz has never accepted funding from pharmaceutical companies, and that will not change. Independence ensures that this commitment is structurally protected, not just aspirational.
HDBuzz’s independence ensures our only obligation is to the HD community we serve.
It also allows us to set our own priorities, respond quickly when news breaks, and continue expanding the ways we serve the community; from in-depth trial explainers to mentorship programs for early-career researchers learning how to communicate science responsibly.
What Changes and What Doesn’t
From a reader’s perspective, very little will change.
All HDBuzz articles will remain:
Free to read
Free to share
Free of ads
Written and reviewed by scientists
Available in 11 languages
Our publication schedule of ~2 articles a week, editorial standards, and disclosure policies remain the same.
Behind the scenes, however, independence means HDBuzz now directly carries costs that were previously handled through fiscal sponsorship. These include accounting, compliance, insurance, governance, and the administrative infrastructure required to operate as a standalone nonprofit. None of these things are flashy. All of them are essential.
Why We’re Asking for Support Now
HDBuzz exists because the HD community believes clear, unbiased science communication matters. As an independent nonprofit, we now rely more directly on that community to sustain the work. Reader donations support:
Website maintenance and security
Professional translation into 11 languages
Conference coverage and real-time reporting
Live presentations to directly deliver research updates to the HD community
Time for writers and editors to read, analyze, and explain complex research
Mentorship programs for young HD researchers learning science communication
Social media outreach to reach families where they are
If just 5% of our readers gave $20 monthly, HDBuzz would be sustainably funded, ensuring that every article remains free and accessible to everyone, everywhere.
There is no obligation and no minimum. Whether it’s a one-time donation or a monthly contribution, support at any level helps carry this work forward.
Looking Ahead
HDBuzz entered independence at a pivotal moment for Huntington’s disease research. As 2025 showed, scientific progress and regulatory progress do not always move at the same pace. Promising data can coexist with disappointment, uncertainty, and frustration. In moments like these, clear explanation matters more than ever.
Our commitment is unchanged: to serve the HD community with accuracy, context, and respect. We will continue to celebrate progress honestly, explain setbacks clearly, and never lose sight of the people living with the consequences of these developments.
HDBuzz began as an experiment in trust: that families wanted real science, explained plainly, without hype or fear. That trust has carried us to this moment. As we step forward as an independent organization, we do so with gratitude, responsibility, and optimism, and with deep thanks to everyone who has supported HDBuzz along the way.
If you value what HDBuzz provides, please consider supporting our next chapter. Together, we can ensure that independent, unbiased HD research news remains available to the entire community.
This was a year that tested the resilience of the Huntington’s disease (HD) community, with 2025 being remembered for landmark highs followed by disappointing lows shadowed in confusion. Data from clinical trials produced the strongest evidence yet that we can slow disease progression, offering families concrete hope that changing the course of disease is possible. However, just 6 weeks later, the FDA reversed its regulatory guidance and blocked the originally agreed upon path to approval, delivering crushing disappointment to the HD community. Yet the community’s response was extraordinary: over 45,000 petition signatures and unified advocacy from major HD organizations demonstrated that this field won’t accept setbacks quietly.
Beyond the AMT-130 rollercoaster, 2025 brought advances across multiple huntingtin-lowering therapies, revolutionary insights into how CAG repeats expand and can be targeted, actionable health strategies backed by new research, and HDBuzz’s own transformation into an independent nonprofit. As we close out this remarkable year, we’re left with complex feelings – hope tempered by regulatory reality, scientific progress shadowed by bureaucratic obstacles, but also a community more unified and determined than ever. Let’s dive into what made 2025 so unforgettable.
The AMT-130 Story: Hope, Whiplash, and Community Response
Without doubt, the most memorable story of 2025 for the Huntington’s disease community is that from uniQure, bringing us landmark trial updates followed shortly by halted regulatory advancement from the FDA. Despite the whiplash, uniQure remains committed to advancing AMT-130 for the treatment of HD.
For families who have watched loved ones decline year after year with no way to intervene, this felt like vindication. After decades of research, disappointing trial results, and dashed hopes, here was real, quantifiable evidence that suggested HD’s relentless progression might be slowed.
AMT-130 is a one-time gene therapy delivered directly into the brain by surgery. It uses a harmless virus (AAV5) to deliver genetic instructions that cause brain cells to destroy the messenger RNA for huntingtin (HTT), thereby reducing production of both normal and expanded HTT protein that causes disease. The therapy is designed to last a lifetime: one surgery, one dose, and cells should continue making the HTT-lowering machinery on their own.
The topline data showed approximately 75% slowing of disease progression as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS), which tracks motor function, cognitive performance, and daily living capacity. Additionally, participants seemed to show stabilization or improvement in neurofilament light (NfL), a biomarker of brain cell health that typically rises as HD progresses.
While there are some caveats to remember, like this data was from a small number of people and compared against a natural history control group, this was the first time any drug had shown this degree of slowing of HD progression on clinical measures in alignment with FDA standards. Families, researchers, and clinicians around the world celebrated cautiously, knowing that regulatory approval was still needed, but for the first time in a long time, hope felt tangible.
This was a year that tested the resilience of the Huntington’s disease (HD) community, with 2025 being remembered for landmark highs followed by disappointing lows shadowed in confusion.
The Road to September: FDA Alignment and Regulatory Progress
These steps forward for AMT-130 success didn’t come out of nowhere. Earlier in 2025, uniQure had been working closely with the FDA to define a pathway for accelerated approval. In June, the company announced they remained aligned with the FDA on several critical points:
The cUHDRS and NfL could be used as measures of therapeutic benefit
Data from ongoing HD-GeneTRX trials could support a Biologics License Application (BLA)
An external control group from Enroll-HD (a natural history study) could be used instead of requiring an additional placebo-controlled trial
This alignment was significant not just for AMT-130, but for the entire HD field. For the first time, the FDA clearly defined what success looks like, which included positive changes in cUHDRS and improvements in NfL levels.
November 3: The Rug Pulled Out
Then came November 3. In a brief press release, uniQure announced they were no longer aligned with the FDA on using an external control group to support their BLA application. The FDA, which had explicitly accepted this approach as recently as June 2025 according to a previous uniQure press release, had reversed course. They now wanted more robust, traditionally controlled data before considering approval.
This was a confusing and disappointing outcome for much of the community. This wasn’t about new safety concerns or efficacy problems, because the scientific data hadn’t changed. AMT-130 still appeared safe, well-tolerated, and potentially disease-modifying. But now the regulatory pathway in the US, which had seemed clear just weeks earlier, was blocked.
For a community that has endured generations with no way of stopping this disease, this felt especially cruel. The FDA seemingly provided guidance in multiple Type B meetings that the Phase 1/2 data with external controls would be sufficient. UniQure appeared to follow that guidance. And now, at the finish line, it seems the rules had changed.
The impact went beyond drug discovery. Many families from the US who had allowed themselves to see a potential future without HD, some of whom were making life decisions based on the possibility of treatment, were left reeling.
December: The Community Responds
With the confusing disappointment around uniQure, the Huntington’s disease community has united, bringing forth a Statement of Unity from many major HD organizations and petitions that have garnered tens of thousands of signatures quickly. The HD community is standing up and demanding all potential treatments move forward as quickly as possible.
Over 45,000 people signed Change.org petitions urging the FDA to reconsider, to recognize the severe unmet medical need, and to allow uniQure to submit their BLA under the Accelerated Approval pathway using existing Phase 1/2 data. You can find those petitions HERE and HERE.
Major US-based HD advocacy organizations issued a Statement of Unity, proposing to coordinate efforts with regulatory agencies. Many American organizations that often work independently came together with one voice: this community deserves better than regulatory whiplash.
On December 4, uniQure received the official FDA meeting minutes from the October 29 meeting. UniQure says they confirm what the community feared, stating that the Phase 1/2 data, as currently structured, were unlikely to support a BLA submission. But they also provided something concrete to work with, including specific feedback that uniQure could use to chart a path forward.
UniQure’s CEO Matt Kapusta emphasized the company’s commitment: “We are committed to collaborating with the FDA to advance AMT-130 to patients and their families as rapidly as possible. The support we have seen these last weeks from the Huntington’s disease community, including patients, families, caregivers, clinicians and advocates reinforces the urgency of the unmet need in Huntington’s disease.”
The company plans to urgently request a follow-up meeting with the FDA in Q1 2026 to determine the path forward. Meanwhile, they’re advancing regulatory discussions in the EU and UK as parallel pathways.
The AMT-130 story of 2025 isn’t over. It’s a difficult reminder that getting safe, effective therapies to patients involves navigating complex regulatory systems that sometimes shift unpredictably.
What This Means
It’s crucial to separate the science from the US regulatory strategy:
The scientific data remain unchanged and promising:
Disease progression appears to slow by 75% compared to natural history controls
Strong safety profile with no new drug-related serious adverse events since December 2022
Levels of NfL seem to show improvement and encouraging functional capacity
The US regulatory challenge is real but not insurmountable:
This represents a delay, not the end of AMT-130’s development
Previous trial disappointments for the HD community involved safety or efficacy failures, and this is different
Multiple pathways remain: possible US reconsideration, EU approval, UK approval, or approval in another jurisdiction
Scientific progress and regulatory progress don’t always move at the same speed
The AMT-130 story of 2025 isn’t over. It’s a difficult reminder that getting safe, effective therapies to patients involves navigating complex regulatory systems that sometimes shift unpredictably.
But it’s also a testament to a community’s refusal to accept disappointment quietly. The 45,000 signatures represent 45,000 people saying, “we’re still here, we still believe in science, and we demand that regulatory processes serve patients, not bureaucracy.”
The HTT-Lowering Pipeline: Multiple Shots on Goal
Similar to a game of billiards, final shots in clinical trials have to be called before the trials begin. These pre-defined endpoints show drug makers are developing medicines with intent. Image credit: Đỗ Huy
The HTT-lowering pipeline continued to expand in 2025, with multiple companies pursuing different approaches to the same goal: reducing levels of the toxic HTT protein. This “multiple shots on goal” strategy means the HD community isn’t dependent on any single therapy succeeding, as several promising candidates are advancing through clinical trials simultaneously.
SKY-0515: An Oral Option Shows Promise
Skyhawk Therapeutics provided encouraging updates on SKY-0515, an oral HTT-lowering drug that works by splice modulation, essentially changing how cells process the HTT RNA message so that less protein gets made.
In September, Skyhawk reported Phase 1 results showing that SKY-0515:
Appeared safe and well-tolerated
Lowered HTT protein levels in a dose-dependent manner, meaning more drug meant more lowering
Achieved greater HTT reduction than has been reported before with a pill
Intriguingly, SKY-0515 may also lower PMS1, a protein involved in CAG repeat expansion. This “two-for-one” approach that may target both the toxic protein and the DNA instability that drives progression makes SKY-0515 particularly interesting, although more data is needed to see if this would be meaningful.
The larger Phase 2/3 FALCON-HD trial launched in Australia and New Zealand, recruiting 120 participants to test SKY-0515 for up to one year, with global expansion planned.
Votoplam (PTC-518): Fast Track Designation and Positive Trends
PTC Therapeutics’ splice modulator votoplam (formerly PTC-518) also showed encouraging progress. In May, the company announced that their Phase 2 PIVOT-HD trial met its primary endpoint, showing that votoplam appears to lower HTT protein levels.
The FDA granted Fast Track designation to votoplam, accelerating the development and review process. Key findings included:
The drug continued to appear safe with no serious adverse events caused by votoplam
HTT levels were lowered through the 12-month mark
Participants showed positive trends in cUHDRS scores
NfL levels remained stable, suggesting potential brain health benefits
PTC and Novartis (who partnered on the program) are preparing for a Phase 3 trial. PTC will complete the ongoing PIVOT-HD trial, while Novartis will lead future studies.
The HTT-lowering pipeline continued to expand in 2025, with multiple companies pursuing different approaches to the same goal: reducing levels of the toxic HTT protein.
Roche: Three Trials
Roche provided updates on GENERATION HD2, their trial testing the antisense oligonucleotide (ASO) tominersen in people with early HD. In April, an independent data monitoring committee recommended that the trial continue with only the higher dose (100 mg every 16 weeks), dropping the lower 60 mg dose.
Importantly, the committee confirmed that tominersen continues to appear safe with no major safety concerns. The decision to continue with just the high dose suggests this dosing regimen shows more promise for potential benefit.
This represents a measured, data-driven approach to finding the right dose following the early termination of the GENERATION HD1 trial in 2021. The HD community watches these developments closely, as tominersen represents one of the most advanced ASO approaches for HD.
Roche also shared that they’ve begun dosing the first participants in POINT-HD, a Phase 1 trial testing RG6496, a selective HTT-lowering ASO that targets only the expanded, disease-causing HTT protein while preserving regular HTT.
The drug works by targeting a specific genetic marker (SNP) found in about 40% of people with HD, delivered by spinal tap. The trial started in New Zealand and Australia and plans to enroll 40 adults with early HD symptoms, with the main goals being safety, tolerability, and measuring expanded HTT reduction in spinal fluid.
A third trial in which Roche is involved, in partnership with Spark Therapeutics, is testing a one-time gene therapy delivered via brain surgery that uses a harmless virus to lower HTT levels.
The first participant was dosed in June 2025, marking the culmination of years of preclinical work in mice and primates showing the therapy could spread throughout the brain and lower HTT for up to a year. The multi-phase trial will start with 8 participants receiving the treatment in a careful dose-escalation approach, with later phases including a placebo and long-term follow-up to assess both safety and effectiveness.
The Bigger Picture: Multiple Mechanisms, Multiple Chances
The Huntington’s disease clinical trial landscape is marked by a variety of approaches, including gene therapies, daily pills, and antisense oligonucleotides, all with distinct advantages and challenges. This diversity maximizes our chances of developing an effective treatment for HD.
There are also other companies working on HTT lowering approaches who didn’t share major updates in 2025, such as Alnylam Pharmaceuticals, Wave Life Sciences, and Vico Therapeutics. What’s striking about 2025 is the diversity of approaches advancing through clinical development:
Gene therapy (AMT-130): One-time administration via brain surgery
Oral splice modulators (SKY-0515, votoplam): Daily pills that work systemically throughout the body
ASOs (tominersen, RG6496): Spinal injections that target the CNS
Each approach has distinct advantages and challenges. This diversity maximizes the chances that effective therapies will reach patients, while also providing potential options for different disease stages, patient preferences, and clinical situations.
Cracking the Code: Understanding and Stopping CAG Expansion
One of 2025’s most exciting developments happened in understanding some of the fundamental biology now thought to drive HD pathology. Scientists made exciting progress in figuring out how CAG repeats seem to be expanding in brain cells over time, and more importantly, how we may be able to take advantage of that biology to develop possible medicines for HD.
The DNA Repair Paradox
The key insight: some proteins that normally protect our DNA from damage (MSH3, MSH2, MLH3, PMS1) may accidentally be making CAG repeats longer when trying to “fix” them. They recognize the repetitive CAG sequence as an error, but instead of removing it, they copy-paste more repeats.
Meanwhile, another protein called FAN1 can do the opposite, in that it cuts out extra repeats. The balance between these opposing forces seems to contribute to whether CAG repeats grow or shrink in individual brain cells.
This year, researchers reconstructed this molecular tug-of-war in test tubes, providing the clearest picture yet of how this process may work at a molecular level.
2025 brought significant advancements for understanding somatic instability – the expansion of the CAG sequence in the HTT gene that leads to Huntington’s disease. When this sequence becomes too long, the strands no longer line up perfectly. One side can end up with extra “teeth,” creating a mismatch that bulges out from the helix, like a zipper with a kink on one side.
From Biology to Therapeutics
This mechanistic understanding is translating into potential therapies:
MSH3 as a drug target: Multiple groups showed that lowering levels of MSH3 or reducing its function may be able to stop CAG expansion. The lab of Dr. Sarah Tabrizi at University College London published work showing that an antisense oligonucleotide (ASO) targeting MSH3 halted, and even reversed, expansion in brain cells generated from stem cells. Dr. X. William Yang’s group at UCLA knocked out Msh3 in HD mice and completely blocked expansion while improving brain cell changes and behavior. Latus Bio is successfully moving forward with their work, the next steps for which are to submit an Investigational New Drug application from the FDA for their MSH3-targeting gene therapy.
CAG interruptions: A stem cell study showed that inserting CAA “interruptions” into long CAG stretches may be a feasible therapeutic approach, as it seems to stop expansion and improve cellular problems. While this approach is in very early stages, this study suggests that the purity of the CAG DNA sequence, not just the expanded protein length, contributes to disease. Some people naturally carry these interruptions and have later symptom onset.
The Bottom Line
2025 transformed somatic instability from an interesting biological observation into a potentially druggable target. Multiple therapeutic strategies are now in development to stop, or even reverse, the CAG expansion that appears to contribute to disease progression. This represents an entirely new angle of attack on HD from what we currently have in the clinic, separate from HTT lowering but potentially complementary to it.
Actionable Health: What You Can Do Today
Heart Health is Brain Health
While we don’t have a disease-modifying treatment in hand yet, there are actionable things people with Huntington’s disease, or the gene for HD, can do today to improve their health and delay disease onset. A healthy lifestyle, nutritious diet, and regular exercise to maintain heart health have also been shown to improve brain health.
The research examined the American Heart Association’s “Life’s Simple 7” factors (diet, physical activity, nicotine exposure, BMI, cholesterol, blood sugar, and blood pressure) and found striking connections to brain health. While it’s critical to note that this study wasn’t done on people with HD, it supports the fact that taking care of our bodies is good for our brains.
For every 1-point increase in cardiovascular health score, study participants had 3.5% lower NfL levels. Those with the highest heart health scores had nearly 19% lower NfL than those with the lowest scores.
In a 10-year follow-up, participants with low cardiovascular health scores saw NfL increase by 7.1% annually, while those with high scores had a slower increase of 5.2% per year.
The message for HD families is that heart-healthy habits like regular exercise, balanced diet, maintaining healthy weight and blood pressure may genuinely influence brain health and the rate of neuronal damage. While this study wasn’t specific to HD, NfL is used as a biomarker across neurodegenerative diseases, making these findings directly relevant.
While rigorously tested for people HD, studies in the general population link the following with better overall health:
Aim for 150 minutes of moderate exercise weekly
Eat a diet rich in vegetables, fruits, whole grains, and healthy fats
Monitor and manage blood pressure, cholesterol, and blood sugar
Maintain a healthy weight
Avoid smoking and limit alcohol
Get regular checkups
The message for HD families is that heart-healthy habits like regular exercise, balanced diet, maintaining healthy weight and blood pressure may genuinely influence brain health and the rate of neuronal damage.
The Importance of Sleep
Multiple studies published in 2025 revealed that sleep disturbances in HD start earlier than previously recognized and treating them might make a real difference.
A 12-year study following people with the HD gene but no obvious symptoms found:
Sleep disturbances emerged 10-15 years before predicted symptom onset
Two types of problems: “sleep stage instability” (disrupted sleep architecture) appeared earliest, while “sleep maintenance insomnia” (trouble staying asleep) emerged closer to symptom onset
Sleep maintenance insomnia correlated with worse cognition and higher NfL levels
Sleep stage instability could predict who would develop HD over the next decade with about 70% accuracy
The bidirectional relationship between sleep and neurodegeneration is crucial given that HD causes sleep problems, but poor sleep may accelerate brain decline. This creates a vicious cycle, but also a potential therapeutic opportunity.
While not proven to prevent or delay symptoms of HD, studies in the general population link the following with better sleep:
Sleep hygiene basics: Regular sleep schedule, dark and cool bedroom, avoid screens before bed
Limit stimulants: No caffeine after 2 PM, limit alcohol (disrupts sleep architecture)
Physical activity: Regular exercise improves sleep quality, but not within 3 hours of bedtime
Light exposure: Get bright light in the morning, dim lights in the evening to support circadian rhythms
Consider CBT-I: Cognitive Behavioral Therapy for Insomnia is highly effective and available through apps like Sleepio (free through NHS in UK, covered by many US employers)
Talk to your doctor: If sleep problems persist, discuss whether a sleep study or medication might help
Mental Health and Cognitive Changes
Huntington’s disease can impact mental health. If you or a loved one are struggling with irritability, depression, anxiety, psychosis, or any other emotional problem, there are treatment options available. You can work with your care team to find a treatment option that works for you or your loved one.
Mental health and cognitive symptoms received significant attention in 2025, with multiple articles exploring how HD affects thinking, emotion, and psychological well-being.
Psychosis: A study found that psychosis symptoms affect about 1 in 6 people with HD and may change how movement symptoms like chorea manifest. Understanding these symptoms helps break stigma and reminds us that each person’s HD journey is unique.
Irritability: Research explored how irritability in HD is a brain-based symptom that can escalate into severe storms of emotion. Understanding the neurobiology can help families respond with compassion rather than frustration.
Emotion recognition: HD can disrupt how people recognize and process emotions in others, affecting social interactions and relationships. This isn’t intentional, it’s a measurable brain change that family members benefit from understanding.
Staying mentally active: Research suggested that cognitive engagement, like learning new skills, social connection, challenging activities, may help slow cognitive decline. While not a treatment, staying mentally active provides “cognitive reserve” that may maintain function longer.
Acceptance and Commitment Therapy (ACT): An HDBuzz Prize-winning article by Nicolo Zarotti explored how ACT improved psychological well-being for both a person with HD and their caregiver, demonstrating how mental health interventions can complement biomedical advances.
Mental health and cognitive symptoms received significant attention in 2025, with multiple articles exploring how HD affects thinking, emotion, and psychological well-being.
If you or a loved on is struggling with mental health issues or challenging cognitive changes, you could consider:
Working with a therapist who understands neurodegenerative disease; don’t wait for a crisis
Explore evidence-based approaches like ACT, which helps people engage with their values despite difficult circumstances
Join support groups (virtual or in-person) to connect with others facing similar challenges
Recognize that symptoms like irritability and emotion recognition difficulties are brain-based, not character flaws
Caregivers: prioritize your own mental health and remember that you can’t pour from an empty cup
Stay socially connected and cognitively engaged through hobbies, learning, and meaningful activities
Biomarkers: Measuring What Matters
2025 brought advancements in biomarkers – biological metrics that change with disease progression. Identifying and characterizing biomarkers for Huntington’s disease enables scientists to track disease progression and measure if potential treatments are working effectively.
NfL: An Impressive 14-Year Study
A 14-year longitudinal study confirmed that neurofilament light (NfL) is a powerful tool for tracking HD progression. The study demonstrated that NfL can signal disease progression many years before symptoms start, making it an incredibly sensitive biomarker for both understanding disease and testing treatments.
NfL levels are increasingly used as a key measure in clinical trials (as seen in trials for AMT-130), and the FDA has accepted NfL alongside cUHDRS as evidence of therapeutic benefit. Being able to detect these subtle changes in NfL before symptoms of HD are overtly apparent means that we may soon be able to start clinical trials in people with HD when they are much younger, before disease onset.
EEG and MRI: Windows into the Brain
HDBuzz Prize winners highlighted how:
EEG recordings reveal brainwave differences in people who carry the HD gene even before symptoms appear
These non-invasive imaging techniques complement fluid biomarkers, like NfL, providing multiple ways to track disease, which is critical for testing and advancing interventions.
Beyond HTT Lowering: Alternative Approaches
Stem Cells from Teeth
A small Phase II trial from Brazil tested an unusual approach: infusing people with HD with dental pulp stem cells obtained from human teeth. The therapy, called NestaCell, appeared safe with no serious side effects linked to treatment.
Both treated groups appeared to show better movement scores than placebo, and the higher-dose group may have improved in functional capacity. However, the study was small (26 participants total), and the mechanism by which dental stem cells might help HD is unclear.
This is early-stage research requiring larger, controlled trials before conclusions can be drawn, but it represents creative thinking about cell-based therapies.
SOM3355: Symptom Management
While many people are understandably focused on disease-modifying therapies, symptom management remains crucial for quality of life. SOM3355, a drug originally developed for other neurological conditions, received encouraging regulatory signals from both the European Medicines Agency and the US FDA following a Phase 2 trial. The hope is that the drug will help successfully treat HD chorea as well as mood-related symptoms, like anxiety.
A Phase 3 trial is in preparation. If successful, SOM3355 could become a new option for managing symptoms caused by HD.
Sertraline: Multiple Mechanisms?
Research suggested the common antidepressant sertraline (Zoloft) might have effects beyond mood. When scientists dug into the Enroll-HD database, they found the drug may improve function in people with HD. They also carried out studies in mice that model HD and found that sertraline may prevent motor problems and stabilize protein production. While more research is needed, this raises the intriguing possibility that some existing medications might impact HD through unexpected mechanisms.
Nurturing the Next Generation: Mentorship and Fresh Voices
A focus for HDBuzz in 2025 was on training the next generation of science communicators through the HDBuzz Writing Prize and working with recipients of the Huntington’s Disease Foundations HD-CAG award. Communicating research findings to the people who need it most – families with HD – is a critical skill for scientific trainees. Image credit: Mikhail Nilov
The HDBuzz Prize for Young Science Writers
2025 marked the return of the HDBuzz Prize for Young Science Writers, this year sponsored by the Huntington’s Disease Foundation (HDF). The competition invited early-career researchers, PhD students, postdocs, early-stage investigators, and clinicians, to write about HD research in accessible language.
The prize serves multiple goals:
Diversify voices: HD researchers come from varied backgrounds with different perspectives on data
Train communicators: Science communication is a critical skill often neglected in training
Engage the community: Fresh voices bring energy and new angles to explaining complex science
2025 Prize Winners
Prize winners published articles throughout the year, bringing attention to emerging topics:
Chloe Langridge highlighted the protein SGTA as a potential therapeutic target, adding to the growing list of “support proteins” that may indirectly improve disease effects.
These mentorship programs, both the HDBuzz Prize and HD-CAG partnership, represent an investment in the future of HD research. They recognize that scientific progress requires not just brilliant experiments, but clear communication, diverse perspectives, and a pipeline of talented investigators committed to the field for the long haul.
Mentoring HD-CAG Award Recipients
Beyond the HDBuzz Prize, 2025 saw HDBuzz partner with the Huntington’s Disease Foundation’s HD-CAG (Huntington’s Disease Career Advancement Grant) program. This inaugural program supports senior postdoctoral researchers bridging the difficult transition to independent investigators.
HDBuzz has been working with these HD-CAG awardees, mentoring them in science communication and featuring their articles on the website. This partnership ensures that the next generation of HD researchers not only conducts excellent science but can also communicate it effectively to the community that needs it most.
The Bigger Picture
These mentorship programs, both the HDBuzz Prize and HD-CAG partnership, represent an investment in the future of HD research. They recognize that scientific progress requires not just brilliant experiments, but clear communication, diverse perspectives, and a pipeline of talented investigators committed to the field for the long haul. The articles published in 2025 from these young researchers prove that the future of HD science is in capable, creative hands.
Conferences: Where the Community Gathers
Scientific meetings and conferences are where scientists share their latest Huntington’s disease research, before it’s published in scientific journals. HDBuzz reporting from these events ensures the HD community has the most current updates on HD science. Image credit: Jerry Turner, CHDI
CHDI HD Therapeutics Conference (February 2025, Palm Springs)
The 20th annual CHDI meeting showcased significant advances across therapeutics development, with over 400 scientific experts convening to discuss:
Clinical trial updates on HTT-lowering approaches
Advances in genetic modifiers and DNA repair targeting
Biomarker development and validation
Innovative technologies like CRISPR delivery systems
HD Clinical Research Congress 2025 (October 2025, Nashville)
Early-phase results from multiple therapeutic programs
These gatherings serve as idea greenhouses, nurturing collaborative relationships and refining research priorities. The value lies not just in results presented, but in connections built and directions set.
Community Talks
In 2025, HDBuzz delivered research updates directly to the HD community through live presentations and interactive sessions.
Our team delivered talks at three major conferences across the globe: the HDSA National Convention in Indianapolis, US; the Huntington Society of Canada National Conference in Niagara Falls, Canada; and the HDYO International Young Adult Congress in Prague, Czech Republic, where we translated the latest clinical trial developments and research breakthroughs into accessible science for diverse audiences.
We also engaged directly with community questions through a live social media takeover for the Huntington’s Disease Foundation and an ask-me-anything style webinar for HDSA, creating opportunities for real-time dialogue about the science that matters most to HD families.
HDBuzz in 2025: Independence, Growth, and Community Support
HDBuzz generated a record 100 articles in 2025!
A Year of Transformation
2025 marked HDBuzz’s most ambitious year yet. One year into new leadership under Dr. Sarah Hernandez and Dr. Rachel Harding, the organization underwent dramatic growth and transformation:
Doubled article output: From roughly 2 articles per month to a consistent twice-weekly publication schedule (Mondays and Thursdays), matching the accelerating pace of HD research. HDBuzz generated a record 100 articles in 2025!
Expanded the writing team: Brought in new writers from top research institutions, diversifying perspectives and expertise across the HD field.
Launched new platforms: Expanded our reach with a new social media manager to Instagram, Bluesky, and LinkedIn, meeting readers where they are and reaching broader audiences across multiple social media channels.
Established independent governance: Formed an advisory board and completed transition to standalone 501(c)(3) nonprofit status, ensuring long-term sustainability and independence.
Revitalized mentorship programs: Launched the HDBuzz Prize for Young Science Writers (sponsored by HDF) and partnered with HDF HD-CAG awardees to mentor the next generation of HD researchers in science communication.
Our Spring fundraising campaign, “Hope in Full Bloom”, launched in anticipation of major clinical trial results expected in Q2 2025, raising funds to ensure HDBuzz could provide comprehensive, real-time coverage of pivotal updates from various clinical trials.
Our Fall campaign, “Falling Into Hope”, following the September AMT-130 announcement and subsequent November regulatory setback, emphasizing HDBuzz’s crucial role as an unbiased source during moments of both hope and disappointment. Funds raised helped support continued independence, website updates, social media expansion, and our mentorship programs.
Why Independence Matters
HDBuzz has officially become an independent 501(c)(3) nonprofit, achieving the independence that is critical to remain an unbiased news resource, reporting on research updates and clinical trial news for the Huntington’s disease community.
HDBuzz has never accepted funding from pharmaceutical companies. This policy ensures the unbiased reporting that is especially critical as we approach the era of disease-modifying therapies. When regulatory decisions shift unexpectedly (as happened with AMT-130), or when trial results disappoint, families need a trusted source that reports facts without conflicts of interest.
Reader donations support:
Website maintenance and updates
Translation into 11 languages
Presence at conferences for real-time reporting
Time for writers and editors to read, research, and create content
Mentorship programs for young researchers
Social media outreach to expand global reach
The Model Going Forward
If just 5% of HDBuzz readers gave $20/month, the organization would achieve independent sustainability. Every article will always remain free and accessible – no paywalls, no ads, no pharmaceutical funding. Just clear, accurate, accessible HD research news supported by the community it serves.
Our transition to independence in 2025 positioned HDBuzz not just to survive, but to thrive as HD research enters its most exciting and complex phase yet.
HDBuzz has never accepted funding from pharmaceutical companies. This policy ensures the unbiased reporting that is especially critical as we approach the era of disease-modifying therapies.
Looking Forward: What 2026 May Hold
The AMT-130 Question
The regulatory pathway for AMT-130 remains the biggest unknown. UniQure plans to meet urgently with the FDA in Q1 2026 to determine what’s needed, whether that’s additional data from existing trials, a new trial design, or some middle ground. Simultaneously, they’re advancing discussions with European and UK regulators, which may move faster than the US pathway.
The outcome will have implications beyond just AMT-130. It will shape how other HD therapies, particularly gene therapies, navigate regulatory approval. The community is watching closely and won’t hesitate to make their voices heard again.
Phase 3 Trials Launching
Multiple therapies are preparing to enter or are already in Phase 3:
These advanced phase trials represent diversification of the pipeline, giving us multiple shots on goal with different mechanisms and delivery methods.
DNA Repair Targeting Moves Forward
The explosion of mechanistic understanding around somatic instability in 2025 sets the stage for therapies specifically targeting CAG repeat expansion. Latus Bio’s IND submission for their MSH3-targeting gene therapy is just the beginning. We expect more companies to enter this space in 2026, joining those already working here, like Rgenta Therapeutics, LoQus23 Therapeutics, and Harness Therapeutics.
If just 5% of HDBuzz readers gave $20/month, the organization would achieve independent sustainability.
What We’ve Learned
Looking back at 2025, perhaps the most important lesson is this: scientific progress is real but insufficient on its own. Getting therapies to patients requires navigating regulatory systems, manufacturing scale-up, insurance coverage, surgical capacity, and countless other challenges that exist outside the laboratory.
The HD community has proven it can unite when necessary, that it won’t accept disappointments quietly, and that it understands both the science and the bureaucracy well enough to fight effectively. This year has highlighted that those qualities matter as much as any clinical trial result.
The Bottom Line
The road ahead holds both challenges and promise. While we don’t know exactly what that journey will bring, we know that the Huntington’s disease community travels it together, armed with more knowledge, more therapies in development, and more reasons for hope than ever before.
2025 will be remembered as a year of extremes. September 24, the day uniQure announced AMT-130’s positive results, gave the HD community something it desperately needed: evidence that slowing HD progression is scientifically possible. Six weeks later, November 3 delivered a crushing blow when the FDA reversed course on the regulatory pathway. And in December, the community’s extraordinary response with 45,000+ petition signatures and unified advocacy from major organizations showed the resilience and determination that has always defined HD families.
The AMT-130 saga taught us painful lessons about the gap between scientific achievement and regulatory approval. But it also demonstrated something powerful: this community will not accept setbacks silently. Families are demanding that regulatory processes serve patients, not bureaucracy.
Our transition to independence in 2025 positioned HDBuzz not just to survive, but to thrive as HD research enters its most exciting and complex phase yet.
Beyond AMT-130, 2025 was about so much more:
Multiple therapies advancing through the pipeline, each with distinct mechanisms and potential
Deepened understanding of how CAG repeats expand and how we may be able to stop that process
Actionable insights into heart health, sleep, and mental wellness
Young researchers bringing fresh perspectives to HD science
A community pulling together to support independent science communication
The snowflakes of individual studies continue compacting into a glacier of progress. No single discovery will solve HD, and the path forward isn’t as smooth as we’d hoped for in September. But the accumulating progress is real, and it’s transforming what we know is possible.
As we enter 2026, families facing HD carry both hope and hard-earned wisdom. We’ve learned that promising data doesn’t guarantee approval, that regulatory systems can shift unpredictably, and that patience is demanded even when time is the one thing many families don’t have. But we’ve also learned that the science is advancing, the tools are sharper, and this community’s voice is louder and more unified than ever before.
The HD community has proven it can unite when necessary, that it won’t accept disappointments quietly, and that it understands both the science and the bureaucracy well enough to fight effectively.
Disease-modifying therapies for HD are no longer theoretical. They’re in trials, showing real effects in real people, and working through (admittedly complex) regulatory processes. The path isn’t straight, and there could be more challenges to navigate ahead. But with continued community advocacy, scientific rigor, and collective determination, meaningful treatments are coming.
2025 showed us that changing the course of Huntington’s disease is possible. It also showed us that possible doesn’t mean easy. But this community has never had the luxury of easy. We know we have to keep fighting, keep hoping, and keep demanding better. And that matters more now than ever before.
