HDBuzz

⏱️6 min read | Most people with HD report sleep problems, & new research suggests sleep quality is linked to many aspects of living with the disease. Wearables tracked people with HD for a year & revealed better sleep & strength training might help.

⏱️6 min read | Ever wonder when to expect the next update from a clinical trial for Huntington’s disease? The HDBuzz Trial Tracker puts future updates for HD trials on a clear timeline, with deeper explanations in our articles when you want them.

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? 

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.

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.

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.”

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.

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.

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