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.

March 2025 was packed with groundbreaking discoveries in Huntington’s disease (HD) research, and we’re here to bring you the biggest highlights! From the cutting-edge CRISPR delivery system RIDE, which could rewrite the playbook on gene editing, to major advances in drug development, biomarker breakthroughs, and fresh insights into HD biology, this month was a whirlwind of progress. Scientists are pushing the boundaries of what’s possible, inching closer to real solutions for HD families. March not only brought us scientific progress, but also community events, like HDYO’s International Young Adult Congress and Factor-H’s Gratitude Day, that raise awareness about HD, provide a platform of support, and bring the community together. If you missed any of the exciting updates, don’t worry—we’ve got you covered. Dive into our March recap and catch up on all the HD news you need to know!

CHDI

Every year CHDI hosts one of the largest HD research conferences. The 2025 HD Therapeutics Conference showcased significant advancements in research and potential therapies for HD. Over three days, more than 400 scientific experts from around the world convened to discuss clinical trial updates, genetic modifiers, and innovative technologies.

Day 1: Progress in Clinical Trials

The conference began with updates on therapeutic trials targeting huntingtin (HTT), the protein responsible for HD. Researchers shared data on ongoing efforts to reduce HTT levels safely, including small molecule drugs and gene therapies. Discussions also focused on refining clinical trial design, selecting meaningful biomarkers, and ensuring that future trials are better equipped to detect therapeutic benefits.

Day 2: Genetic Modifiers and Disease Progression

The second day explored genetic factors that influence when HD symptoms begin and how the disease progresses. Scientists presented findings from large-scale genetic studies identifying key modifiers that may delay disease onset, offering promising new therapeutic targets. Advances in understanding DNA repair pathways and their role in HD progression were also highlighted, providing new directions for potential treatments.

Day 3: New Technologies and Future Directions

The final day spotlighted cutting-edge technologies that could revolutionize HD research and treatment. Talks covered advances in gene editing, innovative drug delivery methods, and AI-driven approaches to analyzing HD progression. Researchers emphasized the importance of collaboration and continued innovation to translate these discoveries into real-world therapies.

The conference reinforced the growing momentum in HD research, with scientists and industry partners working together to turn breakthroughs into meaningful treatments for families affected by HD.

Wake up call: Sleep is impacted before Huntington’s disease symptoms appear

A recent study, highlighted during Sleep Awareness Week, reveals that sleep disturbances can occur in individuals carrying the HD gene up to 15 years before the onset of other symptoms. Researchers observed that those less than 15 years from predicted symptom onset experienced fragmented sleep and increased nighttime wakefulness, while those more than 15 years away may not show significant sleep issues. These findings suggest that early sleep disruptions may contribute to thinking and mood impairments associated with HD, highlighting the potential of sleep-focused interventions to improve quality of life and possibly slow disease progression.

Listening for Whispers: How a Tiny Protein Could Transform HD Research

A recent 14-year longitudinal study has demonstrated that neurofilament light (NfL), a protein released by damaged brain cells, can serve as an early indicator of HD progression. Elevated NfL levels were detected in individuals carrying the HD gene many years before the onset of symptoms, correlating with disease advancement. This finding suggests that monitoring NfL through simple blood tests could revolutionize HD research by predicting symptom onset, enhancing clinical trial design, and enabling earlier therapeutic interventions to potentially slow or halt disease progression.

The Huntington’s Disease Youth Organization’s World Congress: Supporting Young People Affected by HD

The Huntington’s Disease Youth Organization (HDYO) supports, educates, and empowers young people affected by HD. HDYO’s recent biennial International Young Adult Congress provided a unique space for connection and learning. At the 2025 Congress in Prague, attendees engaged in workshops, heard from leading researchers, and shared personal experiences, fostering a strong sense of community.

HDBuzz gave two presentations, firstly setting the stage with HD research terminology 101, then diving into an overview of important research going on at the benchside and in the clinic. Key themes in other talks included mental health, genetic testing decisions, and navigating family dynamics, with experts offering guidance tailored to young people facing HD. The event underscored the importance of youth involvement in research, advocacy, and peer support, reinforcing HDYO’s mission to empower the next generation of HD families.

Gratitude Day

Factor-H is a nonprofit dedicated to supporting HD families in Latin America, where extreme poverty and lack of resources make the disease even more devastating. This month, HDBuzz caught up with Factor-H founder, Dr. Ignacio Muñoz-Sanjuán, in an interview that details the unique problems that people with HD there face, and how they help and support these vulnerable families.

The organization provides humanitarian aid, medical care, housing improvements, education, caregiver training, and legal advocacy to some of the most vulnerable HD communities in Venezuela, Peru, and Colombia. These same communities played a crucial role in the discovery of the HD gene in 1993, yet many still lack basic necessities. Factor-H also works to combat stigma, educate the public, and advocate for sustainable, long-term support.

A key initiative is Gratitude Day, held this year on March 23rd, which honors HD families’ contributions to research while raising awareness of their ongoing struggles. The 2025 event included a live stream from Venezuela, candlelight vigils, and medical outreach, reinforcing the importance of global solidarity. Factor-H’s mission highlights the need for both immediate relief and systemic change, ensuring that hope and humanity—not just hardship—define the future for HD families.

Molecular Surgeons for Huntington’s Disease Catch a RIDE with CRISPR Advancements

A groundbreaking gene-editing technology called RIDE (Ribonucleoprotein Delivery) is showing promise for treating HD. RIDE uses CRISPR, a powerful tool to edit DNA, and delivers it precisely to targeted cells in the brain, overcoming key challenges like off-target effects and immune responses. Early tests in mice and monkeys have demonstrated that RIDE can effectively reduce harmful HTT protein levels in the brain, leading to improved behavior and motor function. This system offers lasting effects from a single injection and is designed to minimize the risks of unintended genetic changes. While still in early stages, RIDE’s targeted approach brings new hope for HD treatments, with the potential for broader applications in genetic diseases.

March was an exciting month for HD research, filled with groundbreaking discoveries, inspiring community events, and promising advancements toward better treatments. We hope you enjoyed this recap and feel as energized as we do about the increased pace of progress being made. Science is moving fast, and every step forward brings us closer to real treatments for HD families. Stay tuned to HDBuzz for the latest updates in HD research, and as always, thank you for being part of this journey with us!

Imagine a tiny, microscopic surgeon moving through the body, making precise genetic repairs exactly where they’re needed. That’s the vision behind a groundbreaking new gene-editing delivery system called RIDE—Ribonucleoprotein Delivery—recently featured in Nature Nanotechnology. This system offers a novel way to deliver CRISPR, a powerful gene-editing tool, to specific cells in the body. Researchers have tested RIDE in mice and monkeys, with promising results for diseases like Huntington’s disease (HD). Let’s dive into how this innovative system could shape the future of HD treatments.

CRISPR Challenges

CRISPR has revolutionized the way scientists approach genetic diseases, acting as a molecular “find and replace” tool for DNA. For HD, where an expanded CAG repeat in the huntingtin (HTT) gene leads to breakdown of brain cells, CRISPR could potentially correct or silence the faulty gene. However, several key challenges have stood in the way:

• Off-Target Effects – CRISPR must be highly precise to avoid accidental edits in unintended parts of the genetic code.

• Immune System Response – The body may recognize the CRISPR components as foreign invaders and attack them.

• Targeted Delivery – The therapy must reach the right cells in the brain, specifically nerve cells in the very center of the brain that’s most affected in HD, without affecting other tissues.

RIDE aims to overcome these hurdles by packaging CRISPR into engineered particles that have been given brain-specific navigation systems that lets them go to specific cell types.

How RIDE Works

RIDE delivers CRISPR in the form of ribonucleoproteins , which are pre-formed complexes of the editing enzyme and guide RNA—think of this like the genetic navigation system that directs RIDE exactly where to go. The complex is packaged inside a virus-like particle, which acts as a protective car. These particles can be engineered with molecular tags, similar to putting a precise street address in your car’s navigation system, so that they target specific cells, ensuring precise delivery.

The key innovation of RIDE lies in its ability to be customized for different cell types. By modifying the outer shell of these nanoparticles with specific molecular tags, scientists can direct them toward desired cells, ensuring that the CRISPR machinery reaches the correct targets. This is a big leap forward for CRISPR-based gene editing.

To visualize the process, imagine a package being delivered. Current CRISPR approaches can make deliveries to the right neighborhood, but RIDE is a door-to-door service that drops the package at the exact address. RIDE’s customization allows the CRISPR machinery to be sent exactly where it’s needed, reducing off-target effects and improving efficiency.

Testing RIDE for HD

Researchers tested RIDE in mice that model HD, focusing on neurons in the striatum—the central brain region most affected by HD. The goal was to silence or edit the mutated HTT gene that causes HD to slow or stop disease progression.

The results were striking: treated mice showed a reduction in HTT protein levels and improved behavior compared to untreated HD mice, such as their movement control on obstacle courses. Importantly, the editing efficiency was much higher than what has been achieved with other delivery methods that don’t have a cellular navigation system, and there were fewer signs of unwanted genetic changes or immune responses.

Another promising aspect of RIDE is its potential to provide long-lasting effects. All the results in these mice were achieved with just a single injection of RIDE; they didn’t need to continuously administer the treatment. They monitored the mice for over 110 days (which is quite a long time in a mouse’s lifespan!), and the improvements persisted.

An important safety component of the RIDE system is that the gene-editing tools are delivered as an assembled complex rather than as genetic material. This means that it’s only around for a short time, long enough to do its job, before being quickly degraded by the cell’s natural processes—another big leap forward for this CRISPR-based gene editing approach. This reduces the risk of persistent off-target effects that could arise from prolonged CRISPR activity.

Beyond Mice

To really assess the potential of RIDE for treating HD in humans, the researchers needed to move beyond mice. That’s where the monkey studies come in. These studies help get a better understanding of how RIDE might behave in a system that’s more closely related to humans.

Safety was the top priority considering this treatment involves injecting something directly into the brain. They used MRI scans to look for any signs of brain damage after a RIDE injection, and they didn’t find any. They analyzed brain tissue samples and found that RIDE was in fact able to reduce levels of the non-expanded HD protein in the targeted areas. So they’re seeing consistent results in both mice and monkeys, which is a good sign.

The researchers also went a step further to confirm that RIDE could work in human cells. To do this, they used stem cells that they turned into neurons. These studies checked many of the boxes that suggested this technology is working: they were able to target and edit the HD gene and there were surprisingly minimal off-target effects. So they got the green light for RIDE in a human-based model as well.

What This Means for HD Families

While these results are promising, RIDE is still in early stages of development. Further studies in larger animals, and eventually human trials, will be necessary before this approach can be considered for clinical use.

However, this study is a major step forward in the field of gene therapy. It demonstrates that RIDE has the potential to be a safe, effective, and highly targeted method for delivering CRISPR-based drugs. And the researchers are already exploring ways to expand RIDE’s capabilities, including the potential to use systemic delivery.

Systemic delivery could mean scientists would be able to inject RIDE into the bloodstream and have it reach cells within the brain. This would be incredible, and a game-changer for HD and many other genetic diseases. Research breakthroughs around CRISPR are moving quickly—this technology has the potential to change the landscape of medicine as we know it.

Looking Ahead

RIDE represents an exciting step forward in the search for effective HD treatments. By combining the precision of CRISPR with an advanced delivery system that targets specific cell types and shuts off after editing, scientists are getting closer to making genetic therapies for HD a reality. And this team isn’t the only one working on this type of approach.

While we’re still in the early stages of this research, this breakthrough brings new hope to the HD community. This study offers a glimpse into a future where we might be able to treat genetic diseases, like HD, with unprecedented precision and effectiveness.
Stay tuned for more updates on how gene-editing technologies like RIDE continue to evolve and push the boundaries of what’s possible in HD research.