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We know that lifestyle factors – like exercise, sleep, and alcohol consumption – can have an impact on the onset of Huntington’s disease (HD). Another lifestyle factor that people frequently wonder about is diet. A recent review explores the idea that “time-restricted eating”, an approach that limits meals to a specific window each day, could have therapeutic potential for HD. The idea is that timed eating might impact several biological systems affected by HD to improve brain function. But don’t hold the dinner bell, because most findings reviewed in this paper are from animals that model the disease, not from people, and there are some real risks to consider with this approach for people living with HD. Let’s dig into what they found and why you should be cautious. 

Huntington’s Disease: A System-Wide Challenge

HD is a devastating inherited condition caused by a genetic change in the huntingtin gene. This change leads to the production of a faulty protein, known as expanded huntingtin, which can clump together and cause widespread damage in the brain and body.

The symptoms are broad and progressive: uncontrolled movements, trouble with balance, memory, and thinking, and a range of psychiatric symptoms. What makes HD especially hard to treat is how deeply it affects various systems of the body; not just the brain, but also muscles, the heart, and the digestive tract.

Many drugs currently being tested in clinical trials zero in on a single molecular aspect of the disease or are only designed to hit the brain. It’s possible that in order to effectively treat HD long term, we may need a system-wide shift, which is where diet could come into play. 

Some Caveats Up Front

We frequently get asked about the role that diet plays in HD: What’s the best diet to delay onset and dampen symptoms? Has anyone looked into the ketogenic diet? Or the Mediterranean diet? A high fiber diet? We also frequently get asked about intermittent fasting. 

While there have been clinical trials testing some dietary supplements, like creatine and coQ10, those trials were halted for futility. The bottom line is that there are limited robust studies in people around diet as it relates to HD, onset of the disease, or the impact on symptoms. Because of that, most of what we know around these questions is from animals that model HD, and this is the scope of what is reviewed in this paper. 

Thus, everything we discuss in this article must be viewed under that lens and considered within the context that mice aren’t people. What we learn from animals could be informative, but many findings from animal studies have gone on to not be replicated in humans. 

With that said, it’s widely known that how one eats greatly impacts their life. A healthy diet and lifestyle can improve immune function, mood, sleep, brain function, and more. So it’s reasonable to wonder if altering diet could impact HD. A recent review of the academic literature dug into what others have found around time-restricted eating. 

What is Time-Restricted Eating (TRE)?

Time-restricted eating (TRE) is a form of intermittent fasting. Instead of focusing on how much you eat, TRE focuses on when you eat. A typical schedule might allow meals only between 12 PM and 8 PM with nothing but water, tea, or black coffee outside that window.

Unlike long-term calorie restriction (which is notoriously hard to stick to), TRE is sustainable for many people. Interestingly, studies have shown that even without reducing total calories, TRE seems to lead to real physiological changes, like improved metabolism, reduced inflammation, and can promote better brain health.

In the context of HD, some work suggests that TRE might show promise in animal studies. But how can something as simple as when you eat affect something as complex as a neurodegenerative disease?

Despite the interesting science from animals that model HD, TRE isn’t a one-size-fits-all solution, especially for people with HD. A huge concern is weight loss. Many people with HD already struggle with unintentional weight loss and muscle wasting, so fasting is risky.

Autophagy: The Brain’s Cleanup Crew

One of the main ways TRE could help in HD is by kickstarting a cellular cleanup process called autophagy. Think of it as your cells’ garbage disposal system. Autophagy helps break down and recycle damaged cellular parts, including toxic protein clumps like expanded huntingtin.

In people with HD, autophagy doesn’t seem to work as well as it should. Some researchers think that this contributes to the buildup of harmful protein aggregates that damage neurons. But fasting, especially for long enough to deplete the body’s energy stores, could trigger autophagy.

In mice that model HD, TRE seemed to lead to a boost in this cellular recycling. One study suggested that mice fed on an 18:6 fasting schedule (18 hours fasting, 6 hours feeding) seemed to have more autophagy activity and lower expanded huntingtin levels in their brains. 

BDNF: Fuel for Brain Growth

Another key mechanism of TRE could involve a molecule called BDNF, or brain-derived neurotrophic factor. BDNF helps neurons grow, survive, and connect with one another. People with HD have lower levels of BDNF, especially in vulnerable brain areas like the striatum.

However, some research suggests that TRE might trigger the production of ketone bodies that could prompt brain cells to make more BDNF.

In HD mouse models, intermittent fasting seemed to lead to a 3- to 4-fold increase in BDNF and may have produced benefits, like delayed symptom onset, better motor skills, reduced brain atrophy, and fewer protein clumps. In mice, these changes hint at a potential multi-pronged impact from something as basic as adjusting your eating schedule.

Powering Up: Mitochondria and Metabolism

Changes to cellular energy production is another known effect of HD. Mitochondria, the energy factories of cells, appear to undergo fatigue and damage that causes them to not function properly. TRE may help here too.

Fasting activates a certain protein that could help to build new mitochondria and defend against stress that damages them. In HD models, this activation seemed to lead to more energy production and better protection from cellular damage.

There’s even an early case report of a person with HD who tried a combined TRE and ketogenic diet for nearly a year. He reported improved motor function and fewer psychiatric symptoms. However, this is just one case with a self-reported outcome. The placebo effect can be incredibly strong, so this report should be taken with a healthy pinch of salt. 

Resetting the Clock: Circadian Rhythm in HD

Increasing evidence suggests that sleep disturbances and disrupted daily rhythms appear to be common and worsening symptoms in HD. The body’s internal clock, especially in brain areas like the hypothalamus, seems to be impacted by HD, affecting mood, cognition, and overall health.

TRE could help realign these biological clocks. While light resets the brain’s “master clock,” food timing resets “peripheral clocks” in organs like the liver and muscle. In HD mouse models, TRE seemed to improve sleep patterns, activity rhythms, and even heart rate variability, which all suggest better circadian health.

By aligning these clocks, TRE may ease some of the non-motor symptoms that make HD hard to manage.

Diet clearly plays an important role in overall health, but we don’t yet have enough evidence to prescribe specific eating schedules or meal plans to control HD. For now, food should be seen as a supportive tool, not a stand-alone treatment.

Real-World Concerns 

Despite the interesting science from animals that model HD, TRE isn’t a one-size-fits-all solution, especially for people with HD. A huge concern is weight loss. Many people with HD already struggle with unintentional weight loss and muscle wasting, so fasting is risky.

While the average person needs to consume about 2000 calories per day, people with HD may need to consume 5000 to 8000 calories per day. That’s a massive increase! So while someone without HD might be able to consume 2000 healthy calories in a 6 to 8 hour window, consuming 3 to 4 times that amount would be incredibly challenging for anyone. 

Additionally, TRE may be realistic for people in the early stages of HD, or those who carry the gene but haven’t developed symptoms yet, but those with more advanced HD are likely to experience increased episodes of choking. Combining that with trying to consume a large amount of calories in a short amount of time could induce unneeded stress, pressure, and undue risk.

Food as a Tool, Not Yet a Treatment

While it would be nice to believe we can one day delay or control the onset and symptoms of HD simply by adjusting when or what we eat, we’re not there yet. Diet clearly plays an important role in overall health, but we don’t yet have enough evidence to prescribe specific eating schedules or meal plans to control HD. For now, food should be seen as a supportive tool, not a stand-alone treatment.

Regardless of when you eat, whether you carry the gene for HD, are a caregiver, or just care about brain health, what you eat matters too. Food is medicine. A Mediterranean-style diet, rich in protein, fiber, healthy fats, and antioxidants, has been shown to support gut and brain health, and has been shown to support broader benefits outside the context of HD.

To truly understand the effects of diet on HD, blinded clinical trials would be needed. We would need carefully designed human studies to explore whether TRE is truly safe, sustainable, and effective for people with HD, especially in light of the challenges around calorie intake and choking risks. Until then, the science is compelling, but not yet conclusive.

TL;DR – Key Takeaways

• TRE = Time-Restricted Eating, where all meals occur within a set daily window (e.g., 12pm–8pm).
• TRE is not about eating less, but eating on a schedule without reducing calories.
• In HD mouse studies, TRE was suggested to reduce toxic huntingtin protein levels and improve brain health.
• TRE may boost autophagy (cell cleanup), BDNF (brain growth), and cellular energy and defense.
• TRE studies suggested in mice it could help reset circadian rhythms, potentially improving sleep and HD-related behaviors.
• Major concern: weight loss and choking, which are both associated with HD. 
• Human trials are needed to test safety and effectiveness of any diet-related change for HD.

Learn More

Full research article, “Dietary fasting and time-restricted eating in Huntington’s disease: therapeutic potential and underlying mechanisms” (open access).

This month, Huntington’s disease (HD) research offered powerful insights into how the brain changes over time, and how we might slow or track that progression. From using brain scans, smartphone tests, and even sleep patterns to detect early changes, to exploring new treatment angles like glial cell support, gene editing, and energy repair, scientists are uncovering new ways to fight HD at every stage. Even with the recent regulatory rejection of Prilenia’s pridopidine, studies from this month bring real hope that earlier detection, better monitoring, and smarter treatments may all soon be within reach.

Peeking at huntingtin and learning from a PET study

Researchers recently tested a new brain scanning tool called a PET imaging tracer, basically a tiny molecule that “lights up” when it sticks to the harmful huntingtin protein, which causes HD. By tracking this glow in brain scans, scientists hoped to see how much of the harmful protein builds up in people with HD. While the tracer was safe and didn’t cause side effects, it was a little too “sticky,” attaching to places it shouldn’t, kind of like glitter getting everywhere, which made the results harder to interpret.

Even though this particular tracer didn’t produce the results they hoped for, the study taught scientists a lot about how to design better ones. They found that comparing brain regions to the cerebellum (a part of the brain that’s usually spared in HD) helped reveal some meaningful patterns, and that spacing scans a week apart gave more reliable results than doing them back-to-back. For HD families, the big takeaway is this: scientists are getting closer to creating a tool that can track the huntingtin protein in real time, which could one day help monitor how well huntingtin-lowering treatments might be working.

Energy off balance: How Huntington’s disease influences the cell’s powerhouse

Scientists used tiny 3D brain models made from HD stem cells to study how the disease affects early brain development. They noticed that even before brain cells were fully formed, something was off, especially in the way cells made and used energy. A key energy gene called CHCHD2 wasn’t working well, which led to stressed-out mitochondria, the parts of the cell that act like power plants, supplying all the energy.

This matters because if brain cells can’t manage energy properly from the very beginning, they may not grow and develop the way they should, which could make them more likely to break down later. But the exciting part was that the researchers found that boosting the CHCHD2 energy gene seemed to fix the problem in these 3D mini-brains, pointing to a new way scientists might protect brain cells early in the disease.

Simon Says Stop: What a Children’s Game Can Teach Us About Early Huntington’s Disease

Scientists turned the childhood game “Simon Says” into a grown‑up test to see how early HD impacts attention and impulse control. People with early‑stage HD played a computer version: shapes flashed on the left or right and they had to press a button based on colour, not location. Tiny sensors on their thumbs detected even the smallest of muscle twitches, sometimes before a person could stop themselves. It turns out, those with early HD weren’t overly impulsive, but they did take longer to react and had trouble paying attention.

This work suggests that early HD doesn’t seem to make people act on impulse, but it does slow down their thinking and makes it harder to stay focused. Spotting these subtle changes could help doctors recognize HD sooner and guide better support strategies. Most importantly, for families dealing with HD, the study is hopeful because it shows that the brain can still control impulses and that early interventions, like therapies or exercises targeting attention, could help people stay more “in the game.”

This month, Huntington’s disease (HD) research offered powerful insights into how the brain changes over time, and how we might slow or track that progression.

Unsung Heroes: Could Glial Cells Treat Huntington’s Disease?

Scientists tested whether healthy human glial cells, the brain’s support crew, could help repair damage from HD. They transplanted glial progenitor cells into the brains of adult mice that model HD. The results were impressive – treated mice seemed to move better, remember more, live longer, and their neurons seemed to behave more like healthy ones.

This work suggests that by boosting the cells around neurons, we may be able to support and improve neuron function, even after symptoms have started. These “helper” cells might release repair signals or improve the brain environment, giving neurons a much-needed boost. It’s early days, but this type of research opens an exciting new potential route harnessing glial cells to heal the brain and using teamwork to fight HD.

Cracking the Case: How a Smartphone “Detective” is Helping Track Huntington’s Disease Progression

Scientists have created a new tool called the HD Digital Motor Score (HDDMS) that turns a smartphone into a “detective” for tracking HD progression. By using simple phone-based tests, like tapping, walking, balancing, and measuring involuntary movements, data is collected right from home. The HDDMS proved to be about twice as sensitive as traditional clinic tests, which means it could spot subtle changes in movement earlier and more reliably.

This could be a breakthrough because implementing the HDDMS would mean fewer clinic visits, smaller and faster clinical trials, and better tools to see if treatments are working, all without leaving your house. For HD families, that’s huge. It’s like having a superpowered magnifying glass in your pocket, potentially helping doctors and researchers catch disease progression sooner and tailor care more precisely.

Stopping the Genetic Snowball: How a simple genetic interruption slows Huntington’s disease

HD is caused by a repeating stretch of the genetic letters C-A-G that gets bigger over time, like a snowball rolling downhill. Scientists used a modified version of CRISPR, a powerful gene-editing tool, to insert a small genetic change in this repeat sequence. In cells and mice, this simple interruption appeared to slow the dangerous expansion and protect brain cells from damage.

This approach tackles one of the root causes of HD, not just the symptoms. By stopping the genetic snowball from gaining speed, this strategy could lead to long-lasting, effective treatments. It’s still too early to know for sure if this approach will work, but this gives real hope that slowing or even halting disease progression may be possible.

When the Brain’s Orchestra Falls Out of Tune: A New Map of Huntington’s Disease Progression

Scientists used a powerful brain imaging tool to map how HD changes the brain’s communication networks over time, and the results look a lot like a symphony falling apart in three acts. In the earliest stages, the brain actually becomes too connected. The team found that different regions talk over each other, like an orchestra playing too loud and out of sync. This “hyperconnectivity” seems to show up decades before symptoms and may be the brain’s way of trying to compensate for early damage.

As HD progresses, those connections unravel. The disease seems to spread along brain circuits, like a bad note jumping from section to section. Eventually, most of the brain’s communication seems to quiet down dramatically, leading to widespread disconnection. Each stage appears to be driven by different biological processes, from early chemical signaling issues to later energy and genetic breakdowns. The big takeaway is that HD doesn’t follow a straight line, it unfolds in stages, and knowing when and how the brain’s “music” starts to falter could help doctors time future treatments more precisely.

Together, these studies bring real hope that earlier detection, better monitoring, and smarter treatments may all soon be within reach.

Pridopidine Hits a Roadblock: EMA Says No to Approval for Huntington’s Disease Treatment

On July 25, 2025, Prilenia and its partner Ferrer received confirmation that the European Medicines Agency (EMA) has rejected their marketing authorization application for pridopidine as a treatment for HD in Europe. The decision aligns with earlier clinical trial outcomes showing that while pridopidine was generally safe and well tolerated, it failed to meet its primary endpoints in key trials, including the most recent PROOF‑HD trial. Although subgroup analyses hinted at modest benefits in Total Functional Capacity (TFC) among participants not on dopamine-affecting medications, those signals were not deemed robust enough to support approval.

Despite this setback, Prilenia and Ferrer have signaled their continued commitment to developing pridopidine, not only for HD but also for ALS. They plan to initiate a new global registrational study, aiming to further evaluate the drug’s clinical benefits across functional, cognitive, and motor domains. While a regulatory refusal represents a significant disappointment for HD families, the broader landscape of HD research remains dynamic and hopeful in 2025 with good news abounding and more trial news expected before the end of the year.

When the Brain’s Clock Breaks: Sleep Disruption and Circadian Chaos in Huntington’s Disease

A 12-year study followed people with the HD gene to see how their sleep changed over time and the results were eye-opening. Before symptoms even appeared, their sleep became unstable, like a broken clock that couldn’t keep time. Closer to disease onset, many had trouble staying asleep through the night. These sleep problems were tied to slower thinking, mood issues, and signs of nerve damage in the brain.

This study suggests that sleep may not just be a symptom of HD, it might play a role in how the disease progresses. Tracking sleep could help spot early warning signs years before symptoms begin, and improving sleep might even help protect brain health. For HD families, the message is clear – sleep is powerful, and it could become part of future strategies to slow or better manage HD.

Sleep is more than a nightly recharge, it is fundamental to brain health. A landmark 12-year study tracking people with the gene for Huntington’s disease (HD) suggests how specific sleep disturbances could be used to predict disease onset and related cognitive decline. Early sleep changes appear to emerge years before symptoms, while insomnia during the night seems to worsen near disease onset. These findings highlight sleep’s contribution to HD and suggest potential new paths for early detection and treatment.

Understanding Huntington’s Disease and Sleep: A Broken Clock in the Brain

HD is a genetic neurodegenerative condition causing progressive nerve cell damage, usually starting in midlife. It brings a mix of movement problems, cognitive decline, and emotional symptoms. Because HD’s genetic cause and typical timeline are known, it provides a rare “model system” to study early changes caused by brain diseases, including sleep disruptions.

Sleep is often overlooked as just passive rest. But imagine your brain’s sleep system as a finely tuned clock. In HD, this clock begins to break down long before symptoms appear. Scientists have known that sleep quality worsens in HD, but the exact timing, causes, and consequences have been elusive. This new study offers a rare, detailed glimpse into the brain’s broken clock and its potential connection to disease progression.

The Study: Following Sleep, Cognition, and Disease Over 12 Years (!)

Researchers followed 28 people with the HD gene but no symptoms (pre-manifest) and 21 people without the HD gene (controls) matched by age and sex. But this wasn’t a one-and-done study – they followed these people for 12 years! That’s a long time! Participants underwent rigorous sleep studies twice in a lab and wore wrist monitors at home for two weeks, providing detailed short- and long-term sleep data.

They also took tests measuring attention, memory, and executive function, and completed mood questionnaires. A blood test was used to measure neurofilament light (NfL), a protein released by damaged nerve cells that research strongly suggests tracks with HD progression. 

Crucially, after 12 years, 15 gene carriers had “phenoconverted”, meaning they developed clear HD symptoms. Comparing their sleep and cognitive trajectories to those who remained symptom-free gave powerful insights.

Sleep is often overlooked as just passive rest. But imagine your brain’s sleep system as a finely tuned clock. In HD, this clock begins to break down long before symptoms appear.

Key Findings: Sleep Disturbances Mirror and Predict Brain Decline

At the study’s start, there seemed to be no major differences in sleep or cognition between gene carriers and controls. But over time, particularly in those who went on to develop clinical signs and symptoms of HD, sleep problems appeared to emerge.

Sleep seemed to become highly fragmented, as if the clock was literally ticking off time, unable to settle into stable stages. Almost 90% of converting participants had “sleep maintenance insomnia”, meaning they were waking frequently after falling asleep and had disrupting restorative rest.

This insomnia seemed to be strongly linked to worse cognition, particularly attention, processing speed, and executive function, skills vital for planning and multitasking. It also seemed to track with higher depression scores and elevated NfL levels, suggesting a potential tie to ongoing nerve damage.

Interestingly, sleep stage instability, the “ticking” disruptions, seemed to start earlier, even before symptoms, and apparently could predict who would develop HD over the next decade with about 70% accuracy. In contrast, insomnia appeared closer to symptom onset but couldn’t be used to predict future conversion.

These findings suggest different sleep problems play distinct roles across the disease timeline, some as early warnings, others as markers of active disease progression.

What Does This Mean? Sleep as a Window and a Target for HD

This study suggests that sleep issues might not just be a symptom but possibly a contributor of brain decline in HD. If sleep maintenance insomnia participates in cognitive problems and nerve damage, treating it early might slow progression or improve quality of life.

Sleep changes, like instability and insomnia, could become valuable early biomarkers, helping identify who is at highest risk before symptoms appear. This opens exciting possibilities for monitoring and intervention.

Strengths and Limitations of the Study

The 12-year follow-up is an extraordinary commitment, offering rare long-term data in a genetically defined population. Combining lab-based sleep measurements with home readings strengthened confidence in the sleep findings.

Grouping participants by actual symptom onset instead of predicted timing improved accuracy in this study. Depth was added with the comprehensive cognitive, mood, and biomarker assessments.

Limitations were that this was a small study of only 28 people, which got smaller at the 10- and 12-year follow ups. This is to be expected with such a long-term study, but this limits statistical power. It’s also important to remember that correlation does not prove causation, so sleep problems could be parallel effects of the disease rather than causes of changes to brain health. It’s also important to remember that this study focused on early stages, so findings might not apply to people with later stages of HD.

These findings suggest different sleep problems play distinct roles across the disease timeline, some as early warnings, others as markers of active disease progression.

Final Thoughts: Fixing the Broken Clock Could Change Everything

This study is a fantastic reminder that sleep is deeply woven into brain health and disease, for people with HD but also for everyone else. We all need a good night’s sleep for optimal brain function, but this is particularly true for those under stress, like caregivers and folks with diseases like HD. In HD, a broken sleep clock seems to precede and parallel nerve cell damage and cognitive decline.

When we recognize sleep as an active player in our brain health, not just a passive symptom of disease, it invites new research and therapeutic strategies. Could improving sleep quality delay HD symptoms or protect the brain? Might sleep measures become early warning signals for multiple neurodegenerative diseases?

The clock is ticking for people with HD. But understanding how it breaks, and how to fix it, could offer new hope in this devastating disease.

TL;DR – What You Need To Know

• A 12-year study tracked sleep, cognition, mood, and nerve damage biomarkers in people with the HD gene.
• Early sleep instability predicted who would develop HD symptoms years later.
• Sleep maintenance insomnia emerged near symptom onset and suggested a link to worse cognition and nerve injury.
• Sleep disruptions seemed to be closely tied to HD progression and might drive brain decline.
• Treating sleep problems could improve outcomes and slow disease progression.
• Sleep measures might serve as early biomarkers for HD and other neurodegenerative diseases.
• The study’s long follow-up and multi-method approach strengthen findings, but sample size was limited.

Learn More

Original research article, “Sleep abnormalities are associated with greater cognitive deficits and disease activity in Huntington’s disease: a 12-year polysomnographic study” (open access).

We learned on July 25, 2025 that Prilenia’s application to the European Medicines Agency’s (EMA) for pridopidine was not accepted for marketing authorization. While this is perhaps not surprising given the data around this drug in clinical trials thus far, it still comes as a great disappointment for the HD community. So what does this mean for the future of pridopidine? Let’s discuss. 

What is Pridopidine?

Pridopidine (previously called huntexil) is an experimental oral drug being developed primarily for Huntington’s disease (HD), and now also for ALS. It was originally thought to act by influencing dopamine signalling with the hope of improving movement symptoms for people with HD.

However, continued scientific research suggested that its effects seem to be mediated by activation of the sigma‑1 receptor (S1R), a protein found in nerve cells that helps manage cellular stress to maintain healthy cellular function. 

Pridopidine Clinical Trials

Multiple trials including HART, MermaiHD, and PRIDE‑HD found that while pridopidine was safe and well tolerated, it failed to meet its primary motor endpoints. Yet post‑hoc analyses, which is a way to examine data after the trial is run, suggested there might have been possible benefits in Total Functional Capacity (TFC) in some people with HD. TFC scores measure how well people can function at tasks like managing their households and finances, ability to work, drive, cook, and do other day-to-day activities. 

Pridopidine works through activation of the sigma‑1 receptor (S1R), a protein found in nerve cells that helps manage cellular stress to maintain healthy cellular function. 

That possibility of a benefit in TFC led to the Phase 3 PROOF‑HD trial focusing on function rather than motor symptoms. Post hoc analyses, like this one which pointed to TFC, are generally not sufficient for drug approval but can give insight into a subgroup of people or a dosage where the drug might be working. 

So while PROOF‑HD did not meet its pre‑specified primary endpoints in the overall population, exploratory subgroup analyses (especially excluding participants on dopamine‐altering medications) showed there may have been some favorable signals on function, cognition, and motor measures, though those results remain inconclusive.

Applying for EMA Marketing

Based on these potential favorable data in a subset of people with HD not on certain medications, Prilienia applied to the EMA for marketing approval in September of 2024. 

This application involved putting together a massive dossier of information that contained all the previous data around pridopidine. If it was approved, that would mean Prilenia would have the right to sell pridopidine in Europe for the treatment of HD. If it was rejected, that would send Prilenia back to the drawing board. 

After Prilenia submitted their application to the EMA, they announced a partnership with Ferrer, a Spanish pharmaceutical company. Their partnership was intended to further develop and commercialize pridopidine.  

So where do we stand?

July 2025 Update

In their most recent update, Prilenia and Ferrer shared that the EMA refused authorization for pridopidine’s marketing authorization application for HD. This means pridopidine will not be sold for the treatment of HD in Europe. 

Despite what will undoubtedly come as a disappointment for many in the HD community, Prilenia and Ferrer emphasized their continued commitment to advancing pridopidine for the HD and ALS communities. In their statement, they said their plan is to initiate a “potentially registrational global HD study” in the near term. 

So it appears that while Prilenia and Ferrer have been dealt a setback, they don’t have plans to discontinue advancing pridopidine for HD. Like you, we’ll have to wait to hear more from these companies about their specific plans. 

Looking Forward

The failure of advancement for any HD drug is a massive disappointment. However, the data around pridopidine suggested this was the likely outcome, at least for now. While we did our best to temper expectations within the community, we understand that many HD families were still holding onto hope. That hope is never misplaced; it’s what drives the entire research effort forward.

At HDBuzz, our job is to share not just the excitement, but also the realities based on the best available science. We don’t take lightly the responsibility of being your trusted source, and we’ll continue to bring you the clearest, most objective updates possible — no hype, no false hope, just real science.

In their most recent update, Prilenia and Ferrer shared that the EMA refused authorization for pridopidine’s marketing authorization application for HD. This means pridopidine will not be sold for the treatment of HD in Europe.

Even with setbacks like this one, 2025 has already been a remarkable year for HD research with positive updates from uniQure and PTC Therapeutics, a trial from Skyhawk Therapeutics advancing, and the first doses being given in Phase 1 trials by Spark Therapeutics and Alnylam. And there’s still more news expected to come! 

Promising trials, innovative approaches, and new insights are on the horizon, all pushed forward by you, the HD community. So don’t give up hope, because the path to progress is rarely straight, but it is still moving forward. And we’ll be here to walk it with you, every step of the way.

TL;DR

The European Medicines Agency (EMA) has rejected Prilenia’s application to approve pridopidine for treating Huntington’s disease (HD) in Europe.

Although safe and well-tolerated, pridopidine failed to meet primary endpoints in several trials, including the Phase 3 PROOF-HD study, though some exploratory subgroup data showed modest signals.

Despite the setback, Prilenia and Ferrer remain committed to developing pridopidine.

Learn more

Original press release (open access).

An international collaboration between world leaders in Huntington’s disease (HD) that spans both academia and pharmaceutical companies is giving us new insight into how HD progresses. This study has given researchers a detailed timeline of how brain connectivity changes in HD. Using an advanced technique called MIND, researchers traced how brain communication networks shift over decades, from a chaotic overdrive to widespread breakdown. They found that these shifts aren’t random, they’re shaped by disease stage-specific changes that unfold in a dynamic, evolving way. Picture the brain as an orchestra, desperately trying to keep the music going, only to fall out of sync as the HD progresses.

Act I: The Brain’s Opening Crescendo – Hyperconnectivity

In the earliest stages of HD, years, even decades before symptoms arise, the brain isn’t going quiet. In fact, it’s playing louder. A new study used a large collection of data from the observational studies TRACK-HD, TrackOn-HD, and the HD Young Adult Study (YAS). These studies aren’t testing a drug, but are rather designed to follow people with HD as they naturally live and age. They have followed hundreds of people without and with HD for many years, spanning people aged 18 to 65 in all stages of HD. This is a huge dataset!

A major finding of this study is that hyperconnectivity, a state where brain regions are over-communicating, is one of the first detectable features of HD. It can emerge more than 20 years before motor symptoms begin, sometimes even in childhood.

You might expect that a brain with HD would steadily lose function over time. But that’s not what this research showed. Instead, the early HD brain looks like an orchestra where multiple sections begin to play too loudly, as if trying to compensate for someone in their section who was a no show. This might be the brain’s attempt to maintain performance despite early, subtle losses in some neurons.

However, just like an orchestra playing too loudly and out of sync, this early overactivity isn’t necessarily healthy. It was linked to changes in neurofilament light (NfL) levels, a marker that tracks with brain health and nerve cell breakdown and can be measured in blood or brain fluid. So while the early hyperconnectivity might reflect compensation, it’s also a sign of stress, suggesting the brain might be straining to keep the music going.

Act II: The Middle Movement – When the Conductor Walks Out

As HD progresses toward the late pre-manifest stage, a sharp transition appears to occur. That initial hyperactivity doesn’t seem to last. The overactive brain networks begin to falter, and the orchestra loses its timing. This is the point in the concert where the conductor might walk offstage, leaving the musicians to drift out of sync.

The study found that in this mid-stage of HD, a new mechanism kicks in: trans-neuronal spread. This is the idea that the disease-causing HD protein might propagate from one brain region to another along neural connections, almost like a bad note spreading from section to section. The brain’s communication network becomes a route for the disease to move and intensify.

Interestingly, researchers identified specific “epicenter” regions of the brain that seemed to play a role in this trans-neuronal spread only in this mid-stage. It’s as if the disease chooses a few critical players in the orchestra to sabotage the rest. But this is a limited window; the epicenter-driven spread fades as the disease continues, reinforcing the idea that HD progresses in distinct stages.

Using an advanced technique called MIND, researchers traced how brain communication networks shift over decades, from a chaotic overdrive to widespread breakdown.

Act III: The Finale in Dissonance – Hypoconnectivity and Breakdown

By the time someone reaches the stage of HD where symptoms are outwardly visible, the music has largely fallen apart. The orchestra is no longer too loud, instead it’s eerily quiet. The study revealed widespread hypoconnectivity, a dramatic reduction in communication across the brain’s major networks. This was observed in 48 out of 68 brain regions, suggesting a systemic breakdown.

The instruments, or more precisely, the brain’s long-range brain cell connections, appeared to no longer be functioning. Think of the violins missing half their strings, the wind section gasping for air, the percussion fading into silence. This breakdown strongly correlates with high levels of NfL, indicating extensive damage to the brain’s wiring.

Yet even here, a few sections persist. The occipital cortex, responsible for visual processing, showed some pockets of increased activity. Unlike the rest of the brain, these changes didn’t correlate with NfL, raising the possibility of resilience or compensation. Maybe a few musicians are still trying to play, even after the rest of the orchestra has gone silent.

Behind the Music: The Cellular Players and Their Shifting Roles

So what drives this shifting performance? The study points to a fascinating interplay between different biological mechanisms that dominate at different stages. Early on, the disruptions are primarily driven by toxic processes within individual neurons. It’s like certain musicians playing the wrong notes, regardless of what the conductor says.

These early-stage disruptions were closely linked to neurotransmitter systems, the brain’s chemical messengers. The study suggested changes in specific systems particularly involved in the brain’s initial hyperconnectivity. These neurotransmitters play crucial roles in learning, memory, mood, and adaptation, suggesting that the brain’s most flexible systems may be first to respond, and first to fail.

As the disease progressed, these players also changed. Neurotransmitters that regulate pain, mood, and reward seemed to be affected in early pre-HD. And in late pre-HD, systems around mood regulation and impulse control seemed to be affected. These findings match with what we know about some of the earliest changes people with HD start to experience.  

In the mid- and late stages, the dominant mechanisms seemed to shift toward genetic disruptions and mitochondrial dysfunction, more systemic issues that impair cellular function across the board. The music becomes not just off, but increasingly impossible to play.

What makes this study so valuable is the large collection of data used from 3 observational studies (TRACK-HD, TrackOn-HD, and HD-YAS), providing a layered and time-sensitive understanding.

A Stage-Specific Symphony of Decline

What makes this study so valuable is the large collection of data used from 3 observational studies (TRACK-HD, TrackOn-HD, and HD-YAS), providing a layered and time-sensitive understanding. So while clinic visits for these observational studies can be laborious, each blood draw, clinical assessment, and research visit provides incredibly valuable information that scientists are putting to good use to better understand HD. It’s time very well spent!

From this work, we’re learning that HD is not a simple, straight-line descent, it’s a multi-act drama with distinct biological players, turning points, and feedback loops. The research suggests that each stage of HD is defined by different mechanisms, from neurotransmitter disruption to cellular communication spread to full-scale network collapse.

It also shows that these changes are trackable over time, with brain imaging and blood-based biomarkers like NfL helping pinpoint when things go wrong. That means future treatments might not just focus on slowing decline, but on targeting the right process at the right time, catching the brain when it’s still trying to play, even if off-key.

TL;DR: The Big Takeaways

• Early HD isn’t quiet, it’s loud. Hyperconnectivity (over activation) appears decades before symptoms, likely as a mix of compensation and early damage.
• The brain acts like an orchestra, first overplaying to seemingly compensate, then falling apart as coordination fails.
• Disease progression is stage-specific. Early on, issues within cells seem to dominate; later, disease spread and systemic breakdown appear to take over.
• Different neurotransmitters seem to play key roles at each stage, with what appears to be distinct impacts on brain connectivity.
• NfL levels track with connectivity loss, making it a useful marker for identifying when the music begins to falter.
• This model opens the door to earlier, more precise interventions, targeting specific processes before full-blown symptoms appear.

Learn More

Original research article, “Cell-specific mechanisms drive connectivity across the time course of Huntington’s disease” (open access).