October 2026: This Month in Huntington’s Disease Research

October was another busy month in Huntington’s disease (HD) research! We learned more about often-overlooked symptoms, explored new ways to track HD progression, uncovered clues about what drives the disease, and heard encouraging early results of a trial of a huntingtin-lowering drug. Here’s our round-up of the research you might have missed.

Beyond Movement: Understanding HD Symptoms

HD is often associated with movement symptoms, but changes in thinking, behaviour and mental health can be just as challenging.

Ever had a song stuck in your head? Now imagine struggling to move on from a thought, question or behaviour, even when you want to. This is called perseveration, a symptom of HD that can cause people to get stuck in repetitive patterns. Recognising that these behaviours result from changes in the brain, rather than deliberate choices, can help families better understand and manage them.

We also learned about catatonia, an uncommon condition that can occur alongside HD. Catatonia can affect movement, speech and behaviour, making it difficult to distinguish from HD symptoms. This matters because catatonia may require different treatment. The key message? Not every new symptom in someone with HD is necessarily caused by HD.

Both stories highlight why recognising the full range of symptoms matters for improving care for people with HD.

Better Ways to Measure and Model HD

How can we better track HD progression and measure whether treatments are working? Two studies explored different ways to improve our understanding of the disease.

One looked at whether changes in speech could help monitor HD. Speaking requires complex coordination across different parts of the brain, and subtle changes may provide useful clues about disease progression. Measuring these changes could eventually offer a simple, non-invasive way to track HD alongside existing clinical assessments.

Another study turned to an unexpected animal model: pigs! Mice have taught us a great deal about HD, but they don’t capture every aspect of the human condition. Studying HD in larger animals may reveal changes that mouse models miss, giving researchers a more complete picture of the disease.

Both approaches could help researchers better understand HD and improve how potential treatments are tested.

Getting to the Root of HD Biology

October also brought new insights into the biology driving HD, particularly the role of DNA repair. The CAG repeatCAG repeat The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD in the huntingtin gene can get longer in certain cells as we age, through a process called somatic expansionsomatic expansion A process in which the CAG repeat in the Huntingtin gene can change over a person’s lifetime in some cells of the body, particularly in the brain.. This is thought to play an important role in HD progression. Surprisingly, some of the DNA repair machinery that normally protects our genes can actually make these expansions worse.

One article explored the complicated relationship between DNA repair and HD, highlighting how processes designed to maintain our DNA can sometimes contribute to disease. Another focused on MSH3, a DNA repair protein involved in CAG repeatCAG repeat The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD expansion. By learning more about its structure and how it works, researchers hope to identify ways to interfere with its activity and potentially slow repeat expansion.

Together, these findings point towards new treatment strategies that could tackle some of the processes driving HD, rather than just its symptoms.

Exploring New Treatment Approaches

Two stories this month explored very different approaches to treating HD: improving disrupted brain circuits and lowering huntingtin proteinhuntingtin protein The protein produced by the HD gene..

Researchers investigated whether adjusting the brain circuits that help control movement could improve movement symptoms in HD model mice. While many experimental treatments aim to address the underlying genetic cause of HD, understanding how changes in brain signalling contribute to symptoms could provide other ways to improve quality of life.

We also heard encouraging early results from a human safety trial of Alnylam’s experimental huntingtin-lowering drug, brezosiran. Brezosiran uses RNA interferenceRNA interference A type of gene silencing treatment in which specially designed RNA molecules are used to switch off a gene to reduce the production of huntingtin proteinhuntingtin protein The protein produced by the HD gene.. In an ongoing Phase 1b trial, a single dose reduced expanded huntingtin levels in cerebrospinal fluidCSF A clear fluid produced by the brain, which surrounds and supports the brain and spinal cord. by around 60% after three months in the highest-dose group.

The early safety results were also encouraging, and Alnylam plans to move directly to a pivotal trial, designed to test whether the drug provides meaningful clinical benefits. This is promising news, although we still don’t know whether lowering huntingtin with brezosiran will slow HD progression. Larger trials will be needed to answer that important question.

The Bigger Picture

October’s research highlights the many different ways scientists are working to better understand and treat HD. From recognising overlooked symptoms and finding better ways to track disease progression, to uncovering new drug targets and advancing treatments through clinical trials, each discovery adds another piece to the puzzle. There’s still plenty of work to do, but progress on so many fronts gives us lots to look forward to!

Summary

• October brought new insights into overlooked HD symptoms, including perseverationperseveration The inability to to change thoughts or actions to match changed plans and catatonia, highlighting the importance of recognising changes beyond movement.
• Researchers explored how speech changes and animal models, including pigs, could help us better understand and track HD.
• New findings about DNA repair and MSH3 offer clues about what drives CAG repeatCAG repeat The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD expansion and how we might slow it.
• Promising early results from Alnylam’s huntingtin-lowering drug brezosiran, alongside research into brain circuits, highlight different approaches to treating HD.