October 2025: This Month in Huntington’s Disease Research
October was an insight-rich month in Huntington’s disease research: additional clarity around uniQure’s AMT-130, mapping how and where HD changes the brain, early mechanistic studies targeting DNA repair, and a major meeting gathering the field.
This month brought new revelations across biomarkers, basic science and community gathering. In particular, we saw how DNA-repair targeting strategies are moving into focus, how gaps in diagnosis are being quantified, and how the annual Huntington’s Disease Clinical Research Congress 2025 deepened connections across the field. Together these developments reflect how far the HD research landscape has matured, and how many fresh paths remain to explore.
Therapeutic & Clinical Research Highlights
A Closer Look: One Month After the AMT-130 Headlines
Four weeks after uniQure’s landmark announcement, the HD community is still abuzz with the news. HDBuzz took a step back to break down what the data truly show, and what remains uncertain.
Early results from the small Phase 1/2 trial suggest AMT-130 may slow HD progression by about 75% in high-dose participants, marking the first evidence that a therapy could alter the course of disease. But promising doesn’t mean proven. The trial’s small size, use of an Enroll-HD comparator instead of a full placebo control, and lack of peer review mean we must interpret these results with caution, and unanswered questions remain about durability, safety, and access.
By untangling the hype from the headlines, a crucial point is reinforced: progress in HD research is real and accelerating, but it happens through steady, careful steps, not sudden leaps. While the news is hopeful, caution is urged when reading headlines about a “cure” or “treatment” that are too good to be true.
Huntington Study Group (HSG) Clinical Research Congress 2025
The October meeting in Nashville offered a wide sweep of updates: new trial designs, biomarker deep dives, community-researcher interactions, and early-phase results that hint at shifting paradigms. And HDBuzz was there, front row, to cover it all. The gathering emphasised the value of sharing early data, aligning endpoints, and building collaborative momentum.
In a way, the congress acts as a greenhouse for ideas, nurturing the seedlings of innovation until they’re ready for field trials. The value here lies not just in the results presented, but in the relationships built and the priorities refined.
Biomarkers, Mechanisms & Population Research
Mechanistic Targeting of DNA Repair in CAG-Repeat Expansion
A study suggests that small molecules targeting the “DNA scanning machines” may slow the expansion of CAG repeats that are the genetic cause of HD. This finding brings insight into the mechanism that may drive onset and offers a potential new therapeutic angle.
This work combines molecules in a tube to get a better idea of how the error-repair processes that cause CAG expansion go awry in HD, giving researchers something tangible to aim drugs at. Of course, many questions remain: What’s the safety profile? How soon could this translate to humans? And in what disease stage could there be the biggest impact?
This month brought new revelations across biomarkers, basic science and community gathering.
How Big Is the Huntington’s Disease Iceberg?
A recent mathematical modelling study asked: how many people carry the HD gene and remain undiagnosed? This work tries to define the “hidden” portion of the iceberg — people with the gene for HD who aren’t diagnosed — insight critical for understanding the full disease impact.
Knowing the size of the unseen population helps us calibrate the real reach of therapeutic development since it’s not just those already diagnosed who are affected by HD, but those yet to be found. It can also help our community leaders better campaign for resources and recognition from their respective governments and healthcare systems.
HDBuzz Prize-Winning Mechanistic Work
October also presented key early-career researcher contributions via the HDBuzz Prize, sponsored this year by the Huntington’s Disease Foundation (HDF):
One article from Gravity Guignard explored how lowering levels of unexpanded huntingtin protein, or the “good” versions, may complicate safe drug development. This work is a reminder that lowering levels of a target must be done with caution.
Another article from HDBuzz Prize winner Chloe Langridge highlighted the protein SGTA as a potential therapeutic target for HD, adding to the growing list of “support proteins” in the cell that may indirectly improve disease effects.
These mechanistic pieces reinforce that the field’s concept of “targeting huntingtin” is evolving into “impacting the molecular network around huntingtin.”
Early Clues in the HD Brain: Mapping Changes from Birth
A recent study used specialized techniques that examine where and how cells in the brains of mice are impacted by HD. They found there are changes at the level of individual cells long before symptoms appear.
The researchers found that gene activity shifts seem to start at birth in HD mice, especially in the striatum and cortex, the brain regions most affected in the disease. Medium spiny neurons may have early over-activation of key identity genes that later decline, while cortical development genes seem to be reduced from the start.
These findings suggest a time-lapse view of HD progression, highlighting that molecular changes begin early but evolve gradually, shaping which cells become most vulnerable.
Themes That Unified the Month
- Mechanism first, translation next — There is a clear focus on understanding how HD works (DNA repair, protein networks). These insights will be critical as treatments that target the functioning of the huntingtin protein translate to the clinic.
- Quantifying the unknown — Whether it’s undiagnosed carriers or untested protein networks, October emphasised measuring the hidden parts of the HD landscape.
- Community and collaboration matter — Big meetings, transparency around complex mechanistic work, and the advancement of research projects with the help of the HD community reinforce that progress happens not in isolation, but through collective effort.
- Cautious optimism with rigour — While the pace of HD research appears to be accelerating, researchers are dedicated to relaying an accurate message to the community and the field is appropriately mindful of safety signals, false leads, and the need for robust data.
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Falling Into Hope
Independent reporting by HDBuzz remains vital, particularly as we advance toward disease modifying drugs. The month of October continued our 8-week giving campaign, “Falling Into Hope”.
With the generosity from the community, we were able to surpass our original fundraising goal of $30,000! Your support helps ensure families everywhere stay informed and empowered as science moves us all forward to an HD-free future. Thank you!
Summary
- New small-molecule work targets DNA‐repair machinery, which is promising but early.
- The Huntington Study Group (HSG) HD Clinical Research Congress 2025 fostered big-picture alignment and data sharing.
- Studies modelling undiagnosed gene carriers highlight hidden disease impact.
- Prize-winning mechanistic work on “good huntingtin” and SGTA show complexity of targets.
- The month emphasised measurement, mechanism and community, in balance.
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