Huntington’s disease (HD) is caused by extra repeats of the DNA letters CAG within the genetic code of the huntingtin gene. We used to think that those CAG lengths were stable in most tissues, but we now have a growing understanding that CAG instability contributes to HD. Somatic instability is the concept that CAG repeats expand over time in some types of cells, particularly cells that are vulnerable in HD. Many scientists think this process might play a role in speeding up the development of symptoms.

A current paper delves into some of the machinery behind this phenomenon, asking how CAG expansion is connected with disease, and how science could harness DNA repair genes as a treatment for HD.

From people to animals… and back to people

Our current understanding of the phenomenon of CAG repeat expansion stems from huge human studies in which participants with HD donated samples and clinical data. Their contributions enabled scientists to link subtle differences in people’s genetics with the age when they developed HD symptoms. These studies, known as genome-wide association studies, or GWAS, (pronounced ‘gee-wass’) showed that certain DNA variations could greatly hasten or delay the onset of HD.

Many of the genes identified in these studies that warranted further research belong to a family of genes that help repair DNA. The past few years have seen a flurry of activity leading us to some new conclusions about HD and expansion of CAGs. Here’s a brief recap before we dive into some novel data around this topic:

• The DNA repair machinery can slip up when trying to “correct” extra-long CAG repeats – accidentally making them longer and longer!

• This does not happen in the vast majority of cells, but seems to occur a lot in a part of the brain called the striatum, which controls mood, movement, and motivation. Studying CAG expansion in the striatum could lead us closer to understanding why these cells are so vulnerable in HD.

• Some studies have found that there is a threshold of around 150 CAG repeats at which damage to the cell starts to speed up.

• Experimental “knockout” or genetic removal of DNA repair genes known to make mistakes on CAGs can slow down or even stop CAG repeat expansion in lab models of HD.

• Some of these genes, like Msh3, are the targets of human HD therapies in development – but we still need to understand more about how they influence HD biology, and what are the consequences (positive and negative) of knocking them out.

Setting up the experiment

The authors of a recent paper, led by X. William Yang at The University of California, Los Angeles (UCLA), took a direct and thorough approach to exploring the connection between DNA repair genes, CAG expansion, brain cell health, and even behavior.

They chose a set of nine genes identified in the human GWAS studies and which form part of the machinery that performs a certain type of DNA repair, the kind that drives the “oops” of CAG lengthening. Then they made use of specialized mouse genetics and breeding schemes to create HD mice missing one or both copies of these DNA repair genes.

In each of these HD mice, missing genes like Msh3, Pms1, Mlh1, and others, they could learn more about how messing with DNA repair might affect CAG expansion, RNA message production (the lab’s specialty), toxic huntingtin buildup, and other features of HD. They were surprised to learn that some knockouts had profound positive consequences, whilst others had no effect at all. What they learned is valuable for our understanding of HD biology and the development of therapeutics.

Reversing RNA changes

Our DNA is read or “transcribed” by specialized machinery to make RNA messages, which are eventually used to make proteins, the building blocks of life. There is a whole branch of science that explores the location and amount of RNA message made from different genes – this is the field of transcriptomics.

Scientists can define a healthy mouse “transcriptome” by looking at thousands of genes and asking which are normally turned on and off in different cells, and how much of each RNA message is present. Then they can look at how this changes in an HD mouse over time, or experiment to see what might help restore the mouse’s RNA levels to normal.

The Yang lab was working with one type of mouse that models HD that shows major changes in its transcriptome compared to regular mice. Lots of genes are producing more or less RNA than they are meant to, especially within medium spiny neurons, the cells that are most vulnerable in HD. When the Yang lab “knocked out” half of the Msh3 and Pms1 in their HD mouse model, they saw a partial reversal of the RNA changes in medium spiny neurons. With Msh3 or Pms1 fully gone, the RNA changes were almost fully reversed, often lasting up to a year (half a lifetime for a lab mouse!). Knocking out a couple of other genes – Msh2 and Mlh1 – also had some reversal effects, but these were more moderate. Some gene knockouts had no effect at all.

Members of the Yang lab are world experts in studying HD transcriptomics, and they used multiple cutting-edge laboratory techniques as well as different statistical approaches to confirm their results. They examined RNA levels across many cells, down to the level of single cells, and also looked at how tightly the DNA was wound around its “spool,” known as chromatin. In all cases, knocking out Msh3 and Pms1 seemed to reverse the HD-related changes.

Calming CAGs and clumps

In parallel, the Yang lab measured the amount of somatic instability – the lengthening of CAG repeats – in different parts of the brain and body. In this type of HD mouse, CAG repeats get longer over time, especially within the cells of the striatum. In fact, this group used statistics to define the rate at which CAGs expand in these vulnerable mouse brain cells: it’s about 8.8 CAG repeats per month. (These rates of expansion do NOT apply to humans – these mice start out with 140 repeats and are designed for experimentation.)

The exciting finding is that when the mice had less or no Msh3 or Pms1, that rate went way down. In fact, removing both copies of Msh3 slowed that rate down to 0.3 extra CAG repeats per month, all the way up to 20 months old – that’s basically a stable repeat length, in an old mouse!

At the same time, Yang and colleagues observed that HD mice with half or no Msh3 or Pms1 also had far fewer clumps of huntingtin protein in the striatum. The buildup of these clumps is a classic feature of HD that many scientists suspect could be toxic to brain cells. Removing Msh3 prevented the formation of huntingtin clumps in other areas of the brain as well. The amount of clumped-up huntingtin seemed to correspond with the amount of abnormal RNA changes they’d previously seen.

Furthermore, they were able to confirm results from other labs showing that there seems to be a threshold of CAG repeats – around 150 – above which the cell begins to experience more stress. They connected this threshold to higher levels of RNA changes: CAG expansion speeds up and worsens that stress.

Preventing brain and behavioral changes

We love math and multi-panel rainbow graphs, but it’s even cooler to see a link between genetics and behavioral health. One way in which this work represents a step forward is that the authors show how knockout of the genes that prevent CAG expansion can also have effects on brain cells and mouse movement.

This type of HD mouse tends to show changes in the connections between neurons, known as synapses, as well as enlargement of support cells called astrocytes. The mice also have problems with their gait and movement. However, when the researchers knocked out Msh3, they no longer observed any of these HD-related changes in the mice. This is even further evidence for Msh3’s role in HD, and suggests that it is a good drug target.

Note that this wasn’t a main focus of the paper – they only looked at a few features of brain health and one behavioral task – but it’s still a promising link.

Small steps power future treatments

You have likely noticed that HDBuzz has been harping on somatic instability (loudly and frequently) for a while now, and that we’ve presented lots of similar messaging: CAG repeat expansion seems to be contributing to HD, and scientists have identified some ways to combat it. This work is no exception; once again, genes like Msh3 and Pms1 are culprits that can be “knocked out” to great benefit in the brains of one type of HD mouse.

All these individual advances may appear to be small, but publications like this one represent years of collaborative work among a large team, shaped by frequent input from an international community of HD scientists. We chose to highlight this particular paper because it connects the dots between CAG expansion, abnormal RNA messages, and changes in brain health and behavior.

The authors caution that we need much more information to truly understand the link between Msh3 and Pms1 and the symptoms of HD. They also acknowledge, as we always do, that mice are not people. These mice in particular begin life with 140 CAGs in every cell of their body, which is much higher than even most cases of human juvenile HD. CAG repeats are not expanding anywhere near as quickly in humans as they do in these experimental mice.

Nevertheless, their data, along with that of other labs working tirelessly to understand HD, makes a strong argument for developing therapies based around Msh3 and Pms1. And these efforts are indeed under way!

We often think of the adult brain like a completed jigsaw puzzle—once all the pieces are in place, that’s it. If a few pieces go missing, as happens in neurodegenerative diseases like Huntington’s disease (HD), there’s not much we can do except try to slow the loss. But new research is challenging that idea in a big way. A new study has shown that it may be possible to grow new brain cells in the adult brain—and not just any cells, but the exact pieces that HD takes away. Even more amazing? These new cells can connect with the brain’s existing networks, as if finding their place in the puzzle and clicking right into place. This discovery opens the door to a bold new goal: not just slowing the loss, but rebuilding the puzzle itself.

What Gets Lost in Huntington’s Disease?

To see why this study matters, let’s start with the pieces that go missing in HD. The disease causes progressive damage to an area of the brain called the striatum. The striatum sits almost exactly in the center of the head and helps control movement, emotions, and decision-making. The specific puzzle pieces lost here are called medium spiny neurons, or MSNs.

MSNs are essential connectors in the brain’s motor circuit. They help organize and relay instructions for smooth, coordinated movement. As HD progresses, these cells die off, breaking key links in the puzzle. The result: jerky movements, trouble thinking clearly, and emotional changes.

For a long time, scientists believed that once MSNs were lost, they were gone for good. But what if the brain has more pieces in the box—just waiting for the right signals to grow and fit into place?

Making New Pieces

That’s exactly what this new study from the lab of Dr. Steve Goldman at the University of Rochester set out to test. The researchers tried something bold: encouraging the adult mouse brain to grow new neurons. Not just any neurons, but the right kind—the ones that fit the MSN-shaped holes in the HD puzzle.

They used two special proteins to create the right environment. One, called BDNF (brain-derived neurotrophic factor), acts like fertilizer for neurons, helping them grow and survive. The other, called Noggin, guides stem cells toward becoming neurons rather than other cell types.

Think of BDNF and Noggin as puzzle guides: one boosts the brain’s ability to make new pieces, and the other makes sure those pieces are shaped correctly. When these were delivered to the brains of adult mice, something remarkable happened: the brain started creating new neurons that looked and acted like MSNs.

Lighting Up the New Pieces

To track these new cells, the researchers used a clever genetic trick that made newborn neurons glow under the microscope. This let them see exactly where new pieces were forming—and whether they matched the shapes of the ones lost to HD.

In mice that received BDNF and Noggin, glowing new cells filled in the striatum. Many of them had the molecular markers scientists know are specific to MSNs. Even more encouragingly, they produced the same kinds of receptors MSNs use to communicate—essential for locking into the brain’s circuitry. It wasn’t just random growth. These were puzzle pieces that actually looked like they belonged.

Connecting the Dots

But pieces alone aren’t enough. For a puzzle to make sense, the connections between pieces matter just as much as the pieces themselves. The brain is no different. So, the next big question was: do these new MSNs actually connect with the right parts of the brain?

Using a safe, specialized version of the rabies virus (yes, really), the scientists traced incoming connections to the new neurons. They found that these newborn cells were receiving signals from all the right brain areas—the motor cortex, thalamus, and more.

Then, they flipped the direction and looked at where the new neurons were sending signals. Sure enough, they were linking up with the globus pallidus, a region of the brain that relies on MSN input to control movement. The puzzle wasn’t just getting new pieces—it was starting to fit back together.

Functional, Not Just Decorative

For the brain, even a puzzle with the right shapes won’t help if the pieces just sit there. To really matter, these new neurons had to be active and firing correctly. So the scientists used high-tech tools—like optogenetics and electrical recordings—to see if the new MSNs were actually sending signals and responding.

The answer? Yes. These weren’t passive bystanders—they were live, working parts of the brain. They could receive and send electrical signals. They acted like mature MSNs. In other words, they functioned.

This is crucial. It means the new pieces didn’t just look right and fit—they helped complete the picture.

Moving the Needle on Symptoms

The final and most important test: could these new neurons make a difference in how the mice moved?

The researchers used a technique called chemogenetics to selectively activate the newborn MSNs. When they did, the mice that model HD—who typically move very little—became more active. Turning on these cells improved movement.

That’s a big deal. It’s like putting a few critical pieces back into a jigsaw puzzle and suddenly seeing the image take shape again. The effect wasn’t just cosmetic; it made a real difference in behavior.

A Piece to Remember

While this work is incredibly exciting for HD families, it’s important to remember that these new cells have the same genetic makeup as the rest of the cells in the brain. So for someone with the gene for HD, that means the new cells will also have the gene for HD. Which means they’ll likely start to show signs and symptoms of the disease eventually too.

The good news is that the newly created MSNs would be developmentally “younger” than the MSNs initially created during brain development. Since HD has a delayed effect, we could expect that the same might be true in the new MSNs. In people, that delayed onset could provide the sort of time to improve health span and extend lifespan.

The less good news is that this means that this type of approach would very likely require multiple treatment rounds to compensate for the continued loss of the new brain cells. But, from where we stand right now, that would be a welcome problem!

Another positive piece of news to keep in mind is that these studies were done in adult mice using a pretty severe HD mouse model. This shows that even in more advanced cases, the right cell population may still be around and able to respond to treatment by BDNF and Noggin. While mice aren’t a one-to-one comparison for people, that’s great news!

What It Means for HD Families

This study doesn’t offer a treatment—not yet. But it completely reimagines what might be possible. For decades, scientists have worked to slow or stop the loss of brain cells in HD. Now, they’re asking: what if we could replace them?

The idea that the adult brain can grow new, functional MSNs—and integrate them into circuits that matter—is a seismic shift. It gives researchers a new strategy. And for people and families affected by HD, it offers something else: hope.

The puzzle isn’t finished. Pieces are still missing. But now we may have found a way to craft new ones—and click them into place. As always, we’ll be following this story closely at HDBuzz, keeping you updated as the picture comes more clearly into view.

Imagine battling a disease that not only affects your body but also causes your mind to lose touch with reality, making it hard to see the world as it really is. This is the heartbreaking reality for many people living with Huntington’s disease (HD) who also experience symptoms of psychosis. Professor Clement Loy and his inspiring team of researchers from the University of Sydney investigated how psychosis symptoms in HD may affect the lives of these people.

Breaking the Silence

HD can cause symptoms across three main areas: mood, mind, and movement. For some people with HD, one of these areas may be more impacted than the others. What’s important to remember is that each person with HD has their own unique journey, much like how every star in the sky is unique. Symptoms and progression can vary from one person to the next.

For some people with HD, mood and mind symptoms can be more intense, and this can sometimes lead to a set of symptoms known as psychosis. A person struggling with psychosis symptoms may experience hearing voices that aren’t there, having hallucinations, believing things that aren’t true, or feeling confused about what is real and what is not.

This can add an extra layer of difficulties for someone who is already struggling with other symptoms associated with HD. Psychosis can be a sensitive topic for some, but by opening up discussions around psychosis, it is hoped that the topic will become more widely understood and talked about.

Shining a Light

An important study by Professor Loy and his team investigated how psychosis symptoms may impact daily life and the progression of HD. They aimed to better understand the challenges faced by people with HD, who also suffer from psychosis symptoms. Beyond the mental toll, the researchers concluded that psychosis appears to have an impact on particular movement symptoms in HD.

The researchers gathered information from people who tested positive for the gene that causes HD – both individuals displaying movement symptoms, as well as individuals who were not yet displaying any movement symptoms.

Over 1,000 participants were invited to complete questionnaires and assessments to measure mood, mind, and movement symptoms, every year, for 5 years.

• Movement symptoms were measured by participants performing different motor tasks, such as walking in a straight line.
• Mind symptoms were measured through an interview with a researcher. This involved remembering and repeating words and following simple instructions.
• Mood symptoms were assessed through a questionnaire. Questions focussed on assessing mental health and behaviour in participants. For example, do they feel sad, nervous, or frustrated?

Different Stars, Different Paths

Around 1 in 6 people with HD, about 18%, in this study experienced psychosis symptoms at some point during their lives. In those people, the researchers found that they had less independence and ability to carry out day-to-day tasks, reduced cognitive ability, and increased behavioural symptoms. This is perhaps unsurprising given the intense effect that psychosis can have on a person’s ability to function, think, and behave.

One of the more surprising findings in this research was that people with HD who experienced psychosis symptoms appeared to experience less uncontrollable jerky movements or uncontrolled twitching. These very common movement symptoms – known as chorea – are often seen in people with HD.

To make sure there weren’t external factors contributing to reduced chorea, the scientists adjusted for the use of some medications, like antipsychotics and tetrabenazine, that can affect movement symptoms associated with HD. However, the authors acknowledge that a limitation of this study is the lack of detail around dose and duration of the use of these types of medications. Even still, this finding highlights how some people with HD will experience very different levels of mood, mind, and movement symptoms. This enlightening research by Professor Loy and his team, reflects back to how unique each person with HD is.

This research has raised interesting questions: Could those who experience psychosis symptoms in HD have different brain chemistry or genetics compared to those who do not experience psychosis symptoms? This is because those with psychosis symptoms did not seem to follow a similar pattern for movement symptoms, compared to those who do not experience these symptoms. Although this study did not provide definitive answers, it does support the idea that HD does not follow a ‘one-size-fits-all’ approach.

Guiding the Way

For individuals and families affected by HD, the presence of psychosis symptoms can be particularly distressing. Caregivers may struggle to understand the sudden paranoid thoughts or when their loved-one is hearing or seeing things that aren’t really there. The person with HD, who is also experiencing psychosis, may feel confused, frightened, or defensive when their reality does not align with others.

If you are a person with HD or if you are a caregiver for someone with HD and relate to some of the psychosis symptoms discussed in this article, you are not alone. There are a number of coping strategies that you can try to help to manage these symptoms better, which could improve quality of life.

Potential Coping Strategies for Psychosis Symptoms

• Medication Management: Antipsychotic medications may help, though their use must be carefully balanced as they can sometimes worsen movement symptoms. If you want to explore the use of antipsychotic medication, please consult a medical professional, such as your psychiatrist.
• Psychological Support: Therapy can help both people with HD and caregivers in managing distressing symptoms.
• Routine and Structure: Providing a predictable, supportive environment may help ease feelings of agitation and confusion for people with HD.
• Open Conversations: Recognising and discussing symptoms without judgment can help increase understanding and reduce stigma of psychosis symptoms.

Shattering Stigma

Psychosis, particularly when linked to a condition such as HD, remains a difficult topic to discuss. There is often fear and misunderstanding surrounding psychosis symptoms. However, studies like this remind us that mental health is just as important as physical health in HD care. By talking openly and honestly about psychosis symptoms, we empower people with HD, their loved-ones, and medical professionals to provide better support and reduce misconceptions.

HD effects both body and mind in deeply intertwined ways. As research continues to unravel the mysteries of HD, understanding the mood and mind aspects, including psychosis, will be key to providing compassionate and effective care. For people navigating the journey of HD, one message remains clear: you are not alone, and your experiences, both physical and emotional, are valid and worthy of support.

Remember, each person living with HD shines in their own unique way, like a star in the sky, adding their light to the world in ways only they can. As we continue to learn and grow together, let this article be a source of strength, compassion, and hope, illuminating the path for others facing similar challenges.

Two recent studies offer fresh insights into how antidepressants, often prescribed to help manage mood and anxiety, are prescribed in Huntington’s disease (HD) and might also influence cognitive decline. One study zooms in on medication use in HD, while the other takes a broader look at dementia and antidepressants. Together, they reveal a complex and evolving map of treatment decisions.

Evolving HD Medication Landscape

The first study examined medication use among people with HD, using data from thousands of people in Enroll-HD, the largest observational study of the disease. Among other things, Enroll-HD collects data on what medications are most commonly used during HD care. One striking finding? A staggering 84% of people with HD use at least one medication, with this number climbing as the disease progresses.

In the early stages, people with HD take an average of 2.5 medications. But as the disease advances, that number more than doubles to 5.2. This really highlights just how much a person’s medical needs change as HD progresses.

So, what medications are people taking? The study found that antipsychotics (used to manage movement symptoms and psychiatric issues), selective serotonin reuptake inhibitors (SSRIs, a common class of antidepressants), and painkillers (for chronic discomfort associated with HD) top the list.

Surprising Factors

But here’s where things get really interesting—prescription patterns vary based on factors like disease stage, gender, and location. For instance, men with HD are more likely to be prescribed antipsychotics, while women tend to use more antidepressants and painkillers.
The geographical divide is equally fascinating: In North America, SSRIs are the go-to choice, whereas in Europe, doctors are more likely to prescribe antipsychotics.

Why? It could be differences in treatment guidelines, cultural attitudes toward medications, or even drug cost and availability. Whatever the reason, this variation suggests that medication choices might be influenced by more than just individual patient needs.

What’s important here is that this study actually looked at what medications people were using, not just what their doctors recommended. So this gives us a much more realistic picture of what’s actually happening. This is valuable because it gives us a peek into the real world, the lived experience of these folks who are dealing with HD on a day-to-day basis.

Treatment Shift

Another crucial takeaway from the study is how medication use shifts over time. Early on, doctors may focus on medications that aim to manage mood and anxiety. But as involuntary movements and challenging behaviors become more prominent, treatment shifts toward managing these more disruptive symptoms.

This shift is particularly evident in the use of antipsychotics, which increase significantly as HD progresses.

Meanwhile, people who develop the rare form of juvenile HD show different medication patterns altogether, often requiring more treatments for aggression and irritability rather than for movement symptoms.

These findings highlight the need for personalized treatment approaches that consider unique disease trajectories and needs of different patient groups, particularly for those with juvenile HD.

Antidepressant Use in People with Dementia

A second study steps back from HD specifically and looks at a broader question: Do antidepressants influence cognitive decline in people with dementia? Antidepressants are often prescribed for people with dementia to help manage the psychological symptoms that come with the disease, like anxiety and depression.

Using data from the Swedish Registry for Cognitive Dementia Disorders, researchers examined whether certain antidepressants might actually accelerate cognitive deterioration. And the findings are raising eyebrows.

Among people with dementia, those taking antidepressants—especially SSRIs—experienced faster cognitive decline. The effect was particularly pronounced in individuals with more severe dementia at the study’s start.

However, it’s critical to note that some other studies have shown conflicting results, which just goes to show how complex this issue is. These findings add layers of complexity for the decision-making process for doctors and patients around the use of these medications, particularly for the most vulnerable groups of people with severe dementia.

More Medicine, Faster Decline?

Interestingly, they also suggest there is a dose-response relationship—meaning that higher doses of SSRIs were linked to an even greater rate of cognitive decline.

Medications like sertraline, citalopram, and escitalopram—widely used SSRIs—were the most strongly associated with cognitive decline. This raises important questions: Are these medications helping more than they’re harming? Should doctors rethink how and when they prescribe them to people with dementia?

Another intriguing twist? The study found that men experienced a steeper cognitive decline on antidepressants compared to women, despite the fact that women are more likely to be prescribed these medications. Additionally, people who were not taking anti-anxiety or sleep medications alongside their antidepressants showed a more pronounced decline. Could other medications be offering some kind of protective effect, or is this just a coincidence? The answers remain unclear, highlighting the limitations of this study and the need for further research.

Things to Keep In Mind

There are some critical caveats for the study that links accelerated dementia to antidepressant use that people need to keep in mind, because this study isn’t a one-to-one comparator for people from HD families.

• First, depression itself is associated with dementia and cognitive impairment, so we can’t really tease apart the chicken-and-egg problem here. The associations between antidepressant use and cognitive decline could be due to the underlying psychiatric condition rather than the drug itself. In other words, people may be prescribed antidepressants because their symptoms are worse or progressing more rapidly – the underlying cause of decline is the brain disease, not the drug. Although the researchers tried to account for this, it’s not something we can entirely rule out.

• Second, dementia severity could itself be contributing to cognitive decline, making it difficult to conclusively say the results they saw were because of the antidepressants. The relationship between antidepressant use and dementia severity is complicated. From the Enroll-HD data described here, we know that treatment and medication use evolves as HD progresses, which should likely be the case for other diseases as well, like dementia.

• Third, different forms of dementia have very different biological causes, like Alzheimer’s, Lewy body dementia, or frontotemporal dementia. But this study grouped these various types of dementia together. This could be masking some of the disease-specific effects that may be at play between the effects of antidepressants and these specific types of dementia. To add to this, HD is also a unique disease which likely has its own individual effects with specific medications. For that reason, it’s important to assess medication effects at the individual disease and patient level, rather than drawing conclusions broadly across a group of diseases.

• Lastly, and perhaps most importantly, this study looked at association, not causation. These types of study designs that aren’t testing medications in a blinded clinical trial have major limitations. They just don’t have the power or rigor to draw black-and-white conclusions about what is happening biologically. However, they are good at making associations between events, like the use of antidepressants and cognitive decline, that can be examined in more detail in future studies.

Don’t Toss Your Meds!

Both studies highlight the delicate balancing act of prescribing medications for neurodegenerative diseases based on the individual. For people with HD and other forms of dementia, medications can provide crucial relief from psychiatric and motor symptoms.

A critical takeaway is that these recent findings don’t mean antidepressants should be abandoned for HD! Rather, they underscore the need for a thoughtful, individualized approach through collaborative relationships between clinicians, patients, and caregivers. Often people close to us know us better than we know ourselves, and this is particularly true for caregivers.

For many people with HD, the short-term risk from depression or challenging behaviours is huge – these are symptoms that can all too easily lead to injury, self-harm, and premature death. Balancing short-term and long-term risks, and the potential harms and benefits from treatment options, is a delicate business demanding full engagement between patients, their loved ones, and medical professionals.

Conversations between HD families and doctors should be open and honest, so that clinicians can remain vigilant, adjusting treatment plans based on the latest research and the evolving needs of each patient. This could also include helping people find access to non-drug treatments, like therapy, support groups, and lifestyle changes.

The Road Ahead

The studies discussed here are a reminder that medicine is never one-size-fits-all. Particularly for HD, medication use is incredibly common and just gets more frequent and more complicated as the disease progresses. Treatment patterns can be so different for various groups, which really highlights the need for open and honest dialog between patients and doctors to develop personalized care plans.

This work also highlights how much we still have to learn about the brain and the interplay between medications and neurodegeneration. More research is needed to untangle these complex relationships, but one thing is clear: Whether in HD or broader dementia care, the goal remains the same—to create a smoother, safer journey for those navigating these difficult conditions.

For now, patients and families should stay informed, ask questions, and work closely with their doctors to ensure that treatments align with their individual needs. Because when it comes to the brain’s roadmap, careful navigation is key to getting where we want to go.

Over the past year, HDBuzz has been evolving, growing, and delivering on its mission—bringing clear, accessible, and accurate Huntington’s disease (HD) research news to families and researchers around the world. From major clinical trial updates to scientific breakthroughs, we’ve been at the forefront, translating complex science into clear, understandable insights. But as HD research advances, so must we. Today, we’re launching our Spring Giving Campaign: “Hope in Full Bloom”—an opportunity for our community to come together and ensure that HDBuzz remains the trusted source for HD research news.

A Year of Growth and Impact

It’s been one year since HDBuzz transitioned to new leadership. In that time, we have:

• Doubled article output on critical HD research developments. If you feel like you’ve been seeing more HDBuzz content than ever before, you’re not imagining it! As the pace of HD research has accelerated, we’ve matched it. In past years, HDBuzz was churning out about 2 articles a month, and recently we’ve settled in to publishing about an article a week. But we’re not stopping there! HD researchers keep cranking out amazing science and clinical trial updates are on a roll, so we’re ramping up too! You may have noticed our Monday/Thursday publication schedule in March, which will be our new norm, so prep your inbox for HDBuzz emails twice a week moving forward.

• Expanded our team by bringing in new writers from top research institutions. As our output has grown, so has our writing team, offering readers perspectives from fresh voices within the HD research community. And we’re excited to expand this initiative too! We’re bringing back the HDBuzz Prize for Young Science Writers this summer, so stay tuned.

• Launched new social media channels (Instagram, Bluesky) to reach more people in new ways. The way people read and receive information is evolving, so we’re meeting people where they are—on new social media platforms. This will help us bring you our same great content in a fresh way while reaching a broader audience across multiple platforms to keep the global community up to date on HD research breakthroughs.

• Strengthened our funding model, raising over $23,000 through direct reader donations since October. Thank you! We’re still working toward financial independence and sustainability, but because of loyal readers and supporters, we’re headed there.

Every article, every update, every social media post represents our commitment to free, accurate, and accessible HD research news—because knowledge is power.

Why This Matters Now

2025 is shaping up to be a pivotal year in HD research!

Major clinical trials are reaching key milestones. The second quarter of this year will bring long-awaited data from multiple trials testing potential disease-modifying treatments. This includes both uniQure and PTC Therapeutics, who are both expected to report critical results by the end of June. Families, advocates, and researchers around the world will be looking for trusted, clear, and independent analysis—the kind of reporting that HDBuzz specializes in.

New discoveries are transforming the field. Researchers are learning more than ever about HD biology, from biomarkers that could get us to preventative trials to the reason behind why HD symptoms takes so long to show up. HDBuzz ensures these breakthroughs are translated into plain language, making cutting-edge science accessible to everyone.

The global HD community depends on accurate, unbiased information. With so much at stake, it’s critical that families have a source they can trust—one that cuts through jargon and provides clear, relevant updates.

The Challenge: Keeping HDBuzz Strong

While our impact is growing, so are the challenges of sustaining independent science journalism.

HDBuzz is funded entirely by donations from HD community organizations and readers. Unlike traditional media, we don’t sell ads or operate behind a paywall. We believe research news should be free to everyone, no matter their location or financial situation.

Importantly, HDBuzz has never accepted funding or support from drug companies. We love drug companies—we’re hoping they help us cure HD! But taking money from any organization dedicated to a particular therapy could give the impression of bias in our reporting, which we diligently aim to avoid.

Our goal is to raise $30,000 by May 27 to keep HDBuzz thriving, expand our reporting, and prepare for the biggest HD research updates of the year.

Here’s how you can help:

• Make a donation today—whether it’s a one-time gift or a monthly contribution. Every dollar fuels HD research news that remains free for all.

• Share our campaign with your network—on social media, in HD support groups, or with friends and family.

• Stay engaged—follow our updates, comment on our posts, and help amplify trusted HD research news.

• Follow us on social media and spread the word—like, share, and invite your friends and family to follow us too. We’re on Facebook, Instagram, LinkedIn, and Bluesky. Every new follower helps expand awareness and support for HD research.

What Your Support Makes Possible

• $10/month helps us translate articles into multiple languages, reaching HD families worldwide.

• $50 supports real-time reporting from major HD research conferences.

• $200 funds an in-depth, expert-written article breaking down the latest scientific data.

If just 5% of our readers gave $20/month, we would be independently sustainable by the end of the year.

Join Us—Hope in Full Bloom for HD Research

Now is the time. With major trial results on the horizon, groundbreaking research happening now, and a growing community that relies on our reporting, we need your support more than ever.

Every donation, every share, and every engagement strengthens our ability to deliver trusted, timely, and independent HD research news.

Donate today to nurture knowledge, grow hope, and advance understanding of HD research.

Thank you for letting us be a part of your journey.