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While Huntington’s disease (HD) primarily affects the brain, the genetic change that causes the disease is present in every cell throughout the body. Because of that, it has influences beyond the brain, including in the gut. Increasing evidence suggests that changes in gut microbes, leaky barriers, inflammation, and nerve signaling may contribute to HD progression. A recent review of published research maps the “gut–brain superhighway” in HD, highlighting where traffic flows smoothly, where it’s blocked, and where detours might offer new treatment options.

How Human Are You, Really?

If someone were to ask you what species you see when you look in the mirror, you would undoubtedly say human. But people are actually made up of more microbes than anything else. Shockingly, there are more microbial cells in your body than human cells. And 99% of the genetic material in your body is from microbes – only 1% of your DNA is of human origin! So it makes sense that when we think about human biology, we should seriously consider the role that microbes play in our health.

Microbes are microscopic organisms, like bacteria, viruses, fungus, or yeast. When we think of such things, we typically think of infections, but most microbes are harmless, and even helpful. The various microbes that live in our gut help us digest various foods, aid with nutrient absorption, and work to develop our immune systems. Increasing evidence also suggests that the gut, and the microbes that live there, can impact brain health. 

The gut is so closely tied to the brain that some scientists call it the “second brain”. This is because there is an extensive network of neurons within our gut that directly communicates with the brain through the vagus nerve. The vagus nerve is the main connection that controls the parasympathetic nervous system. Think of your parasympathetic nervous system as controlling “rest and digest” functions. It helps to regulate digestion, heart rate, and our immune system. 

From the Brain to the Belly: Why the Gut Matters in HD

We tend to picture HD as a one-way street, where the gene that causes HD produces a faulty protein that causes a decline in brain health. But it’s more like a two-way superhighway with lots of back and forth between the brain and the rest of the body, especially between the brain and the gut, referred to as the “gut-brain axis”. 

This road is busy with traffic lanes like the vagus nerve, immune cells, and the “second brain” of the gut. There are vehicles carrying chemical messengers made by gut microbes and border checkpoints such as the gut lining and the blood–brain barrier, which should only let safe travelers through.

In HD, problems at almost every point on this route can slow traffic, let dangerous cargo through, or disrupt communication entirely.

Roadwork and Weak Bridges: Barriers Breaking Down

HD’s faulty protein, expanded huntingtin (HTT), isn’t just in the brain, it’s everywhere, including the gut. This widespread presence may contribute to why people with HD often have symptoms in parts of their bodies beyond the brain, including gastrointestinal problems like chronic diarrhea, constipation, incontinence, and poor nutrient absorption.

Two major “bridges” on our superhighway are affected – the gut barrier and the blood-brain barrier. The gut barrier can become “leaky,” letting microbes or their components escape into the bloodstream. There is some evidence for this in people with the gene for HD before and after they start to show symptoms, seemingly at levels comparable to those in inflammatory bowel disease. 

The blood–brain barrier also shows signs of “loosened bolts” in HD, with fewer tight junction proteins holding it together. When both bridges are compromised, harmful substances from the gut could have a clearer route to the brain. Supporting this possibility, traces of bacterial and fungal DNA have been found in the brains of people with HD after death. While contamination is possible, it suggests that microbes, or at least parts of microbes, might be able to cross compromised barriers of the gut and brain.

Traffic Jams: Inflammation Along the Route

The gut is the body’s largest immune organ. In HD, this immune system seems stuck in overdrive, like a traffic jam of inflammatory signals. Cytokines, which play a role in regulating the immune response and inflammation, seem to be present at increased levels in blood from people with HD, years before symptoms start. Adding to that, higher levels of some cytokines appear to be linked with worse symptoms and lower scores that chart someone’s ability to carry out day-to-day tasks. 

But encouragingly, it seems that some beneficial gut bacteria may be able to dampen this inflammation, acting like traffic police to keep things moving. However more work is needed to understand the exact type of bacteria that could provide a benefit and if we could harness this as a future treatment option for people with HD. 

Inflammation is also seen inside the gut itself, with high levels of a biomarker that signals stress on the gut lining. 

Faulty Signaling: Vagus Nerve Disruptions

The vagus nerve is the main fiber-optic cable of the gut–brain superhighway. It carries both sensory updates from the gut to the brain and calming “anti-inflammatory” signals back down. In HD, low vagal tone, a sign of reduced nerve activity, seems to be present even 20 years before motor symptoms. 

Low tone could worsen inflammation and has been linked to depression, a common symptom of HD. Researchers are asking whether stimulating the vagus nerve could one day be a therapeutic on-ramp.

The Microbial Passenger List: Who’s in the Vehicles?

Studies are suggesting that the gut microbiome in HD has a different passenger list than in healthy individuals. Diversity may be lower, meaning fewer types of microbes, and certain species might be missing or reduced. Less diversity in the gut microbiome has been linked to lower immune function, poorer digestion, and fatigue.

While more work is needed, researchers are starting to tease apart the microbial differences in the gut of people with HD. For example, the presence of certain microbes may be linked to better thinking skills but worse motor symptoms. And there appears to be sex-specific differences in both humans and mice, suggesting men and women may have different microbes present. 

Possible Road Repairs: Interventions in the Works

If the gut–brain superhighway in HD has traffic jams and potholes, the big question is, can we fix it? Scientists are exploring various ideas to get traffic flowing more smoothly. One option is probiotics (adding “good” bacteria) or prebiotics (feeding the good bacteria already there). These are generally safe, but the first HD trial testing probiotics didn’t show big changes in gut health or thinking skills, so more work is needed in this area to know if this might be beneficial. It might be that we need longer treatment or different combinations of probiotics are needed to see an effect.

Food itself could be a powerful repair tool. In HD mouse models, a high-fiber diet seemed to boost thinking skills, lift mood, and improve gut health. But the most striking findings from this study compared a high-fiber diet to a no-fiber diet in mice, which isn’t realistic for people, who are more likely to consume a low-fiber diet by comparison. So more work would be needed to test this theory.

In people, following a Mediterranean-style diet that is rich in fruits, vegetables, whole grains, and healthy fats has been reported by some to improve quality of life and perhaps allow for fewer movement problems. Other diets, like the ketogenic (very low-carb, high-fat) approach or intermittent fasting, have shown mixed results and come with serious risks. It’s a reminder that there’s probably no one-size-fits-all diet for HD.

It’s not just about food, how we live also shapes the gut–brain connection. In HD mice, physical activity and a stimulating environment seem to delay disease onset and slow progression, while also changing the gut microbiome. Even certain antibiotics, if chosen carefully, have shown reduced inflammation and protected nerve cells in lab models. But broad-spectrum antibiotics, the kind that wipe out a wide range of bacteria, can cause long-term damage to gut diversity, so they’re not a realistic option for intervening with the microbiome.

An Overlooked Exit: Oral Health

After the gut, the mouth has the second largest microbial population within the body. While the effect of HD on the microbes in the mouth hasn’t been studied, we do know that as HD progresses, it can become harder to keep up with oral hygiene. This can lead to gum disease, cavities, and inflammation in the mouth.

That might sound like a small problem compared to the challenges of HD, but oral health affects the whole body. Inflammation from the mouth can spill over into the bloodstream, adding to the overall “traffic jam” of inflammation we already see in HD. Over time, this could make gut and brain problems worse.

The good news is that this is an area where we already have easy tools. Regular dental care, help with brushing and flossing, and even specially designed oral probiotics could all help keep the mouth’s microbial community balanced. These simple steps might not just improve comfort and quality of life, they could also help reduce inflammation that feeds into HD’s wider effects.

It’s a reminder that in a complex condition like HD, the most effective “road repairs” might come from surprising places. From the microbes in our gut to the health of our mouth, every stop along the gut–brain superhighway could hold clues, and opportunities, for improving life with HD.

Summary

• The gut–brain axis is a busy two-way superhighway of nerves, immune cells, and chemical messengers.
• In HD, barriers leak, inflammation surges, and microbial balance shifts, potentially influencing disease progression.
• Early studies suggest diet, probiotics, or exercise could one day help, but more research is needed.
• Oral health may be an underexplored but important off-ramp in managing HD’s systemic inflammation.

Learn More

Original research article, “The microbiota–gut–brain axis in Huntington’s disease: pathogenic mechanisms and therapeutic targets” (open access).

For many people raised in families affected by Huntington’s disease (HD), childhood isn’t just about scraped knees and schoolbooks. It can also mean living with uncertainty, emotional turbulence, and a silence that’s hard to navigate. While much of the focus is on the person with HD, a growing body of research is beginning to ask a different question: what about the children in these families? A recent study led by Dr. Ferdinando Squitieri and his team based in San Giovanni Rotondo, Italy, explored how growing up with a parent who has HD, may affect a child’s mental health later in adulthood. Sadly, the answer is yes, and this is a truth that requires our attention.

A Different Kind of Trauma

When we hear the word trauma, we might picture big, dramatic events that are easy to single out and identify. However, trauma can also come from smaller, repeated emotional experiences, especially in childhood, when we are still learning how to understand the world and our feelings.

It is important to remember that HD doesn’t just affect a person’s movement and mind (their ability to think, remember, and concentrate). It can also change how someone reacts emotionally, making them more irritable, withdrawn, or emotionally unpredictable. For some individuals with HD, these changes can appear before an official diagnosis.

For a child, this kind of environment can be deeply unsettling. A parent may lash out or become unusually distant. Imagine a child accidentally spilling their drink and being met with an outburst of anger or sharp criticism. Over time, the child learns to tread carefully, navigating the emotional landscape of the home like a minefield. 

They may not understand why their parent acts this way, and often, no one explains. Families might not know what is happening themselves, or may avoid talking about it out of fear, shame, or stigma.

Looking Back with Adult Eyes

In the study, Dr. Squitieri and his team recruited two groups of adults. One group included 38 people who had grown up with a parent with HD. The other group had 20 people who had no family history of HD or similar conditions.

Each person was asked a series of questions about their background, questions like their parent’s health (if they came from a family with HD), their childhood experiences, and their current emotional wellbeing. The questions gently explored whether someone had experienced abuse or neglect. They also asked about topics surrounding mental health, including anxiety, low mood, or stress, specifically focussing on how each person felt in the present day.

Researchers used statistics to look for patterns in the answers people gave in the questions. They compared different people who were in the same group, to see how people from different families with HD responded. They also compared responses between the two groups (people from families with HD and people from families who did not have HD). This enabled the researcher to understand whether there were links between childhood experiences and adult mental health.

People who had grown up in families with HD were more likely to experience emotional and psychological challenges in adulthood. This included feelings of low mood or overwhelm, and in some cases, trouble with thinking clearly or feeling connected to reality.

Emotional Echoes That Last

People who had grown up in families with HD were more likely to experience emotional and psychological challenges in adulthood. This included feelings of low mood or overwhelm, and in some cases, trouble with thinking clearly or feeling connected to reality.

However, what really stood out was why people from families with HD were struggling with their mental health in adulthood. The researchers found that it wasn’t always physical abuse or big, traumatic events that predicted mental health difficulties later in adulthood. 

More often, it was emotional abuse or neglect, things like constant criticism, hurtful words, or growing up in a home where emotions felt unsafe, unpredictable, or simply too difficult to talk about.

For children from families with HD, emotional experiences may shape how a person feels for decades to come.

Putting Feelings into Words

It is easy to read findings like this and feel a sense of heaviness. However, this research provides our HD community with understanding. It names what many people raised in families with HD have felt for years but could not always explain. This reminds us that emotional wellbeing matters, and that children in these homes may need more than just physical or practical support. They may need someone to listen, to believe them, and to help them make sense of what they are experiencing.

For adults who grew up in this kind of environment, it offers validation. If you’re struggling with mental health today, it may not be a personal weakness, or something random. It could be something rooted in your past, something that started subtly, and has stayed with you. But that also means healing is possible. Support is possible, and available.

If you would like to learn more about support systems and resources available for young people impacted by HD, we encourage you to reach out to the Huntington’s Disease Youth Organization (HDYO), who has made available a wide range of resources, including access to peer support and connections to professionals in the community. You can also reach out to the Huntington’s Disease Society of America (HDSA) National Youth Alliance (NYA), who provides youth support groups, education days, and HD awareness. You are not alone, and support is available. 

It is easy to read findings like this and feel a sense of heaviness. However, this research provides our HD community with understanding.

A Quiet Kind of Bravery

Growing up in a family with HD can require a quiet kind of bravery, the kind that doesn’t always get recognised by others. The child who carefully tiptoes around a parent’s mood. The teenager who keeps the family secret. The adult who is still trying to make sense of it all.

This study reminds us that early emotional experiences matter for children growing up in families with HD. “The Things We Carried from Childhood” is not just a metaphor. For many in families with HD, it is a truth they live with every day. 

But carrying something for a long time doesn’t mean you have to carry it alone, or forever. With support, healing is not just possible for adults from families with HD, it is within reach.

Summary

• Growing up with a parent who has HD often means living with emotional unpredictability and silence.
• A study of 38 adults from HD families found higher rates of depression, anxiety, and overwhelm than from people not from HD families.
• Emotional abuse or neglect, not major traumatic events, was the strongest link to adult mental health struggles.
• The findings validate lived experiences and highlight the need for emotional as well as practical support.
• Support and healing are possible through resources like HDYO and HDSA’s NYA.

Learn More

Original research article, “Childhood trauma and psychological distress during adulthood in children from Huntington’s disease families: An exploratory retrospective analysis” (open access).

Huntington’s disease (HD) is typically viewed as a brain disorder, but new research highlights its lesser-known effects on the body, especially on muscles, fat, and nutrition, even in the early stages. A recent study found that people with early HD seem to already show signs of muscle loss, altered fat distribution, and malnutrition, which could contribute to increased dependence on others for day-to-day tasks and cognitive decline. These findings suggest the importance of viewing HD as a  whole body condition and point to new opportunities for earlier interventions and possible biomarkers to track disease progression.

More Than a Brain Disease

HD is known as a genetic brain disorder, caused by an expansion of a DNA repeat sequence in the huntingtin gene. This leads to the production of a toxic protein, which accumulates and causes the well-known symptoms associated with changes in brain function: involuntary movements (chorea), behavior changes, and cognitive decline.

But the genetic change that causes HD is present in every cell within the body, so the disease’s reach goes beyond the brain. Changes in the heart, muscles, and even fat tissue have been documented. These so-called “peripheral” effects, that occur outside the brain and spinal cord, may begin early, chipping away at physical health before obvious symptoms appear.

Digging Into the Data: Muscles, Fat, and Function

A recent paper from a group in Austria explored the effects of HD on the body. The researchers studied 20 people living with early-stage HD (stages 1 and 2) and compared them with people who don’t have the gene for HD. They assessed body composition and strength using tools that measure fat to muscle ratio and handgrip strength. 

They found that sarcopenia, or loss of muscle mass, strength, and function, seemed to be rare and found in only 15% of people with HD. Sarcopenia is age-related and common in elderly folks, which can contribute to their reduced mobility and increased falls. While sarcopenia itself seemed to be rare for people with HD, certain aspects of sarcopenia appeared to be more common: reduced muscle mass was seen in 60% of people with HD and reduced strength was present in 45%.

Despite these changes, most people with HD still had preserved walking speed, a potential sign that loss of muscle and strength could begin silently, before functional decline is visible.

Shedding Fat, and Weight

People with HD also seemed to show progressive fat loss, especially as they moved from early stage 1 to stage 2, which isn’t surprising as people begin to experience increased movements because of chorea. Body weight, body mass index (BMI), and visceral fat (fat around organs) all declined with disease progression.

There was unintentional weight loss reported from 25% of people with HD. This suggests the decline wasn’t due to reduced appetite or difficulty eating alone, and is likely part of the disease process. 

Aside from an increase in calories burned because of chorea, molecular influences could also be at play. Weight loss could be contributed by the expanded huntingtin protein itself. Mitochondria are the cell’s powerhouse, and molecular changes that result from HD have been shown to impact the mitochondria’s ability to produce and store energy, in the brain as well as other tissues of the body. Additionally, expanded huntingtin may directly harm fat cells, alter metabolism, and trigger a form of programmed cell death.

Perhaps the most alarming finding from this recent study was the high rate of malnutrition in people with early HD. Using a standard assessment tool, the researchers found that 55% of people with HD were at risk for or already experiencing malnutrition.

Malnutrition: The Overlooked Risk

Perhaps the most alarming finding from this recent study was the high rate of malnutrition in people with early HD. Using a standard assessment tool, the researchers found that 55% of people with HD were at risk for or already experiencing malnutrition.

And this may not just be a side effect of weight loss, because it was linked to worse outcomes across the board:

• Lower muscle mass and fat
• More severe motor symptoms
• Higher levels of dependence on others for day-to-day tasks
• Executive function deficits (trouble planning or organizing)

This suggests that malnutrition could be a driver of decline, not just a consequence, underscoring how imperative it is to ensure that folks with the gene for HD focus on healthy diet and lifestyle choices that will allow them to maintain muscle mass and nutrition. 

Why Nutrition Is So Hard in HD

However, there are many factors that contribute to nutritional challenges for people with HD. Motor symptoms like chorea can make eating and cooking difficult. Swallowing problems (dysphagia) can begin early and can be subtle. And increased calorie burn, especially in people with more movements, raises daily energy demands.

Together, these factors can create a vicious cycle: less intake, more energy burned, and faster decline. These challenges are further heightened by the lack of research in some of these areas, like dysphagia, which remains understudied in HD despite its importance.

So What Can Be Done?

Thankfully, this study doesn’t just point out problems, it offers solutions too. 

Firstly, people with the gene for HD should seek nutritional support so that they can be screened early and often for malnutrition risk. Food textures can also be selected based on those that are easier to swallow. High-calorie diets and supplements can be considered for those with higher energy demands or those with trouble keeping weight on. And nutrient-rich diets, like the Mediterranean diet, may be beneficial for avoiding malnutrition. 

Secondly, people with the gene for HD should focus early on physical activity to grow and maintain muscle mass. Resistance and endurance training, like walking or cycling, can help maintain strength. Exercise is known to improve motor function, walking, and balance, and may even help preserve brain volume and cognitive abilities.

Focusing on nutritional support and physical activity are more than just quality-of-life interventions, as this new research adds to a growing body of evidence suggesting they could delay functional decline and extend independence.

A Surprising New Tool: Muscles as a Biomarker?

Another exciting possibility raised by this study suggests that muscle mass or strength could potentially serve as a future biomarker for HD progression

Because measuring someone’s fat to muscle ratio is simple and widely available, tracking body composition might one day offer a non-invasive way to monitor this aspect of disease and test the peripheral effectiveness of new therapies, particularly those designed to target huntingtin outside of the brain.

Focusing on nutritional support and physical activity are more than just quality-of-life interventions, as this new research adds to a growing body of evidence suggesting they could delay functional decline and extend independence.

Looking Beyond the Brain

This study begins to reframe how we could think about HD. It’s not just a disorder of neurons in the brain, but rather a systemic condition that impacts every cell, affecting the body and brain in parallel.

And importantly, many of these physical symptoms, like muscle loss and malnutrition, could be impacted in a positive way through nutritional support and physical activity. Weight loss, reduced muscle mass, and malnutrition for people with HD don’t have to be inevitable. With early screening, proper support, and proactive care, we may be able to improve not just longevity, but quality of life.

TL;DR – Key Takeaways

• HD isn’t just a brain disease as it impacts every cell in the body, causing early changes in muscles, fat, and nutrition.
• Even in early stages, 60% of people with HD appeared to have reduced muscle mass, and 25% appeared to have unintentional weight loss.
• Over half were at risk of or already experiencing malnutrition, which was linked to worse motor and cognitive symptoms.
• Exercise and diet are promising interventions with both physical and cognitive benefits.
• Body composition could one day serve as a biomarker for HD progression in future trials.

Learn More

Original research article, “Silent destruction: hidden muscle wasting and body decline in early Huntington’s disease” (open access).

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.