July 2026: This Month in Huntington’s Disease Research

July was a month of hard news and continuing progress in Huntington’s disease (HD) research. The tominersen story, a decade long and with more than 1,500 families behind it, came to a close. Meanwhile, in labs and clinics, researchers kept building the tools and the knowledge that will shape what comes next. Both developments are part of this month’s recap.

Themes that unified the month

The end of a chapter, not the end of the book 

Roche’s announcement that they were ending two of their HD programs was genuinely disappointing, and it leaves behind some unanswered questions. Was huntingtin lowered enough in the brain regions that matter most? Was 16 months long enough? How did participants fare who were on the drug longer? Would a different lowering approach do better? Hopefully we’ll have the answer to these questions, and more, once the full dataset is shared.

Better tools to see what’s actually happening

Two of this month’s articles highlighted the problem raised by Roche’s results: we still can’t directly see toxic huntingtin in a living brain. A new PET tracer and a new set of molecular “grappling hooks” both move that needle. When the central question of a trial is did the drug do enough in the right place, the ability to visualize the target brings a new level of clarity.

One perspective is never the whole picture

Two studies this month, on eating problems and on symptom awareness, landed on the same conclusion from different directions: what a person with HD reports, what a caregiver observes, and what a clinician measures can all differ, and you need all three to capture symptoms accurately.

Clinical trials and treatments

Roche ends two Huntington’s disease drug programs after disappointing results 

Roche announced it is discontinuing development of both tominersen and RG6496. In the Phase 2 GENERATION HD2 trial, tominersen did what it was designed to do biologically, in that it lowered expanded huntingtin as measured in spinal fluid. It also seemed to improve disease biomarkers, with reduced NfL in both spinal fluid and blood. However, participants did not show slowing of disease progression on the cUHDRS or TFCTotal Functional Capacity A standardized rating scale for function in HD, used to assess capacity to work, handle finances, perform domestic chores and self-care tasks at 16 months. Importantly, there were no new safety concerns. However, this is a complete termination of the tominersen program, with no open-label or compassionate-use continuation through Roche. Anyone who participated in this trial who has questions should contact their study site. 

Separately, and for unrelated reasons, Roche stopped POINT-HD, the first-in-human study of RG6496, after longer-term animal studies suggested the drug wouldn’t be suitable for repeated dosing in humans. 

Roche’s gene therapy program, RG6662, continues unchanged, and the company has committed to sharing full data at future medical meetings.

Putting it in print: A clinical trial trying to rein in runaway pruning

Four years after announcing top-line results, Annexon has formally published its Phase 1b study of ANX005 (tanruprubart) in 28 people with HD. The drug blocks C1q, the “on switch” for a tagging system that tells specialized immune cells which synapses to prune. This process appears to run rampant in HD, causing useful brain cell connections to be pruned by mistake. It was generally safe, and it hit its target, lowering C1q and related complement proteins. However, NfLNfL biomarker of brain health results were too variable to interpret. 

An after-the-fact analysis hinted that participants who started with more complement activity stayed more stable, but with 12 and 11 people in those groups, and a study designed to test safety rather than benefit, that’s a signal worth following up, not a result. No larger HD trial has followed, though Annexon tells us HD remains on its radar.

Seeing huntingtin

Are we finally getting that PET we’ve always wanted? 

Not a puppy, a PET tracer that can visualise huntingtin proteinhuntingtin protein The protein produced by the HD gene. clumps in a living brain, the way amyloidamyloid The main protein that builds up in the brains of Alzheimer’s disease patients tracers transformed Alzheimer’s research. CHDI’s previous candidate, CHDI-180R, showed disappointing results in humans last year on specificity and reproducibility. New work evaluated CHDI-385, a tracer with a different structure. In mice it specifically grabbed onto toxic huntingtin, showed up even in young animals with low aggregateaggregate Lumps of protein that form inside cells in Huntington’s disease and some other degenerative diseases levels, and, crucially, gave nearly identical images on repeat scans. A second study showed it could be given multiple times a year while staying under US and European radiation limits. But measuring this new PET in humans will be the real test, and researchers are being appropriately cautious.

Catching a Giant Protein: Five New Ways to Grab Huntingtin 

Huntingtin is enormous, unwieldy to fold, and hard to study. A team from Canada and Japan screened roughly a trillion tiny ring-shaped protein fragments and found five that latch onto huntingtin at five different spots. Cryo-EM gave atom-level pictures of exactly where each one binds. When the researchers used these protein fragments as molecular bait in human cells, they pulled out one partner over and over again: HAP40. Over 3,000 proteins have been reported to touch huntingtin, but this may suggest that the real, everyday form of huntingtin in cells is the huntingtin–HAP40 pair. The rings aren’t medicines, but they’re smaller and cheaper than antibodies currently used in labs as the “gold standard” for attaching to huntingtin. They’re also small enough that they might one day work inside living cells, and they double as blueprints for future molecules that could track or degrade huntingtin. 

Understanding the biology

Joining the Starting Lineup: MutLβ’s Role in DNA Repeat Expansions

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., the continual lengthening of the genetic letters C-A-G over a lifetime, particularly in cells of the brain, is driven by DNA repair proteins doing the wrong job in the wrong place. Using a soccer analogy (aka football for our non-US friends), researchers cast MutSβ as the defender that spots the problem and MutLγ as the attacker that makes the cut. This study promotes MutLβ from bit player to playmaker, as it appears to physically link the other complexes together, boost MutLγ’s cutting activity, and increase expansion four- to five-fold in a test-tube system. Notably, FAN1, the protein that normally protects against expansion, wasn’t included, so how it fits into this lineup is still an open question.

Living with HD

More Than Just Food: The Hidden Challenges of Eating with Huntington’s Disease

Researchers at the University of Hull interviewed 19 people, ten professionals and nine people with HD, some with partners or carers, and found six themes when it comes to challenges around eating and keeping weight on in HD. High-calorie diets and supplements, the standard advice, are often exhausting or unpalatable in practice. Access to specialist support is a “geographical lottery.” Cognitive and mental health difficulties can make shopping, planning, and even starting a meal hard. Choreachorea Involuntary, irregular ‘fidgety’ movements that are common in HD burns energy and makes eating physically difficult; swallowing problems can make it frightening. Mealtimes are social, so eating problems may bring embarrassment and isolation. And some people don’t see weight loss as a problem at all. The authors push for a holistic approach, suggesting this is about dignity, independence, and family-oriented solutions – not just calories.

Mirror, Mirror on the Wall: When Self-Awareness Shifts in Huntington’s Disease 

A team in San Diego asked 60 people with HD and their study partners to rate the same symptoms separately, then compared answers. Reduced symptom awareness, called anosognosia, showed up at every stage, including the earliest: 18% at HD-ISS stages 0/1, 28% at stage 2, and 32% at stage 3. This matters practically, because many clinical trials lean on self-reported surveys. It also matters for families because it shows that anosognosia isn’t denial or stubbornness, it’s a shift in the brain systems that help us notice changes in ourselves.

Summary

• Roche discontinued tominersen after GENERATION HD2 showed biomarkerbiomarker a test of any kind – including blood tests, thinking tests and brain scans – that can measure or predict the progression of a disease like HD. Biomarkers may make clinical trials of new drugs quicker and more reliable. changes but no slowing of disease progression, and stopped RG6496 for unrelated reasons based on animal data
• Roche’s termination of two programs don’t rule out huntingtin lowering as an approach, but they raise sharp questions about how much, how early, where, and for how long
• Annexon published its Phase 1b results for ANX005, suggesting it is safe, on target, with a small post-hoc hint of benefit in people with more active complement systems
• CHDI-385, a new PET tracer for huntingtin proteinhuntingtin protein The protein produced by the HD gene. clumps, performed well in mice with good reproducibility and a safe radiation profile; human testing is next
• Five new ring-shaped protein fragments can grab huntingtin at five different sites, and suggest that huntingtin is nearly always bound to HAP40
• MutLβ is a central player in 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., linking the other DNA repair complexes and boosting repeat growth
• Eating problems in HD are physical, cognitive, emotional, and social all at once, and would benefit from a holistic response
• Reduced awareness of one’s own symptoms appears early in HD, which has real implications for how trials measure progress