June 2026: This Month in Huntington’s Disease Research

June felt like a month where several long-running threads finally started to pull tight. The AMT-130 saga in the United States took a genuinely hopeful turn with the FDA. A stem cell trial opened a new chapter. Lab science continued to ask sharper questions about how to go after toxic huntingtin more precisely. And alongside all of it, the Huntington’s disease (HD) community showed up for HDBuzz in a way that means a lot. Let’s get into everything June brought us!

Themes That Unified the Month

Precision over brute force

Three biology articles this month shared a common thread: the HD field is getting more specific about what to target and how to take it down. PROTACs target expanded HTT clumps without disturbing the healthy protein. An alternate version of the modifier LIG1 slows CAG expansion through more careful, if slower, DNA repair. The theme: smarter, not just harder.

The AMT-130 rollercoaster finds a steadier track

After a tumultuous stretch, June brought welcome news on the regulatory front. The FDA has agreed that uniQure’s existing three-year data can serve as the basis for a Biologics License Application. That’s a real step forward, even with important caveats still in play. For HD families that have been riding this rollercoaster for years, this month felt, at least, like a gentler curve.

A busy month for clinical milestones

June also brought updates from the therapeutic pipeline. SKY-0515 hit 12 months of clinical data with encouraging trends. In a press release, Skyhawk shared durable huntingtin lowering, stable clinical trends, and a global trial enrolling ahead of schedule. Meanwhile, a neural stem cell therapy called hNSC-01 dosed its very first participant in a new clinical trial, opening an entirely novel chapter for cell transplantation in HD. One program accelerates our hope for a huntingtin-lowering pill, while the other begins the clinical chapter of a story that began over a decade ago in the lab. Both are reasons to pay attention.

Beyond the gene: legal gaps, psychological care, and what families actually need

Two articles this month stepped back from the bench to ask broader questions about what the HD community needs to live well. One examined a patchwork legal landscape that can penalize people with the HD gene for knowing their own genetic status. The other looked at how psychological support needs to evolve as HD progresses. Together, this work reminds us that progress isn’t measured only by new therapies, but also by how well we support people living with HD.

Clinical Trial Updates

SKY-0515 Holds Strong at 12 Months

Through a press release, Skyhawk shared new 12-month data from their Phase 1/2 trial, suggesting that their oral splice modulator SKY-0515 continues to lower expanded huntingtin by around 69%. This is essentially unchanged from earlier timepoints, which suggests the effect is durable. Participants also showed small improvements on the cUHDRS clinical scale, maintaining separation from the natural-history decline that we expect to see in people not taking the drug. As a bonus, Skyhawk also reported that SKY-0515 lowers PMS1, a protein linked to somatic CAG repeat expansion, though whether that translates to a clinical benefit isn’t yet known. The pivotal Phase 2/3 FALCON-HD trial, now enrolling across eight countries including an Australia/New Zealand cohort that filled six months ahead of schedule, will be the real test.

The Other Shoe Drops: uniQure Plans FDA BLA Submission for AMT-130

After a difficult stretch, uniQure shared meaningful regulatory news in June. The United States FDA has agreed that the existing three-year Phase 1/2 data can serve as the basis for a Biologics License Application, which the company plans to submit by Q3 2026. A confirmatory study will still be required if approval is granted, and critically, preliminary discussions suggest it may not require a sham brain surgery, though that’s not yet finalized. This doesn’t mean AMT-130 is approved or available, but it does mean the path forward is clearer than it has been in some time. We’ll be watching closely.

First Participant Dosed in Neural Stem Cell Trial for HD

June brought us a new clinical milestone – the first participant has received hNSC-01, a neural stem cell therapy being tested in the REGEN4HD trial at UC Irvine under Professor Leslie Thompson. The Phase 1b/2a study will enroll 21 participants, with doses gradually increasing across four cohorts, and is primarily designed to assess safety. Researchers will also collect exploratory measures, like motor assessments, brain imaging, and levels of NfL and PENK in spinal fluid, to watch for early signs of biological activity. Full data are expected around mid-2028. Cell transplantation has a long and complicated history in HD, so it’s important to note that this is a new generation of the idea, with better manufacturing and more rigorous controls.

HD Biology

Sealing the Gap: A Case for Slower, Smarter DNA Repair

Everyone has slight variations in their DNA that make them unique – some influence traits like height or eye color, while others can affect our health. In people with HD, a natural genetic variant in a modifier gene called LIG1 has been shown to delay disease onset by an average of 7 to 8 years. A new study investigated why. It turns out that this version of the DNA repair protein LIG1 works more slowly and carefully, refusing to bond mismatched DNA tiles that regular LIG1 would let slide. When researchers introduced this more meticulous version of LIG1 into HD mice, those mice showed less somatic CAG expansion than controls. The results add to existing evidence that targeting somatic expansion could be a meaningful therapeutic strategy.

Precision Pruning with PROTACs: Selective Targeting of Toxic Huntingtin

Most huntingtin-lowering approaches reduce both the regular and expanded forms of HTT. A new study took a more targeted approach using molecules called PROTACs, designed to recognize expanded HTT clumps and shuttle them to the cell’s own disposal machinery. In HD cells, one of these PROTACs reduced toxic HTT clumps while leaving healthy HTT intact. In HD mice, it reduced aggregates, improved brain markers, and extended lifespan. There’s meaningful work to do before this could translate to people, but it’s an encouraging proof of concept for selective HTT targeting.

Living with HD

Evolving Needs, Evolving Care: Psychological Support Across HD Stages

A small study interviewed 13 experienced psychologists working in specialized HD care centers to understand what psychological support actually looks like across the disease course, and where the greatest challenges lie. In early stages, care focuses on counseling, genetic uncertainty, and trauma processing. In the middle stages, talk therapy can help with anxiety, depression, and acceptance. In later stages, psychologists shift to working more with families and care teams. Common barriers include cognitive decline, limited self-awareness, avoidant coping, and the lack of HD-specific clinical guidelines. The study also identified what can help, including flexibility, preventive engagement, and multidisciplinary teams.

Your DNA Shouldn’t Cost You Your Insurance

Australia recently passed landmark legislation banning life insurers from using genetic test results in underwriting, which is a protection that most HD families in the United States still don’t have. This article used that milestone to unpack the real landscape for HD families navigating genetic testing and insurance. GINA, the US law commonly thought to provide broad protections against genetic discrimination, only covers health insurance and employment. Life, disability, and long-term care insurance are explicitly excluded. Critically, GINA’s protections also disappear once symptoms appear. In the UK, HD is the only genetic condition for which insurers can require disclosure for high-value life insurance applications. The article also flags a coming wrinkle: as modifier gene testing advances, the insurance implications could extend beyond HD itself. The gap between what the science can tell families and what the law protects them from keeps growing.

From HDBuzz

2025 Annual Report: Here’s What You Made Possible

In 2025, HDBuzz published 100 articles, double our 2024 output and more than triple our historical average, and reached 329,000 unique visitors with 630,000+ page views. We mentored six HDBuzz Prize winners and five HD-CAG fellows. We became an independent 501(c)(3) on January 1, 2026. And, to remain an unbiased source of HD research and trial news, we did all of it without pharmaceutical funding. Read the full annual report on HDBuzz, and if you value what we do, please consider donating at hdbuzz.net/donate.

A Thank You to Everyone Who Supported Fund the Buzz!

Our spring fundraising campaign wrapped on June 15, and we want to extend a genuine thank you to everyone who gave. 276 donors contributed a total of $23,024 to Fund the Buzz, with gifts ranging from $5 to $2,000. The median gift was $25, which is a reminder that this is a community effort in every sense. Every dollar goes directly toward keeping HDBuzz independent, ad-free, and pharmaceutical-funding-free. We’re so grateful, and we don’t take your contributions for granted!

Summary

• The FDA agreed uniQure can submit a Biologics License Application for AMT-130 in the United States, which they plan to do by Q3 2026, with a confirmatory study to follow if approved
• The first participant has been dosed in REGEN4HD, a Phase 1b/2a neural stem cell trial at UC Irvine
• SKY-0515 continues to lower expanded huntingtin by ~69% at 12 months, with encouraging cUHDRS trends persisting
• A new LIG1 study showed that a slower, more careful DNA repair variant reduces somatic CAG expansion in HD mice, adding to therapeutic interest in targeting somatic expansion
• A protein-targeting chemical selectively degraded expanded HTT clumps in HD cells and mice while sparing healthy HTT, extending lifespan in mouse models
• A small study mapped psychological care interventions across HD disease stages, highlighting the need for flexible, stage-matched, multidisciplinary support
• Australia’s new life insurance genetics legislation highlights how far the US, and to a lesser extent the UK, lag behind in protecting HD families who choose to get tested
• HDBuzz 2025 Annual Report: 100 articles, 329,000 visitors, 630,000+ page views, and zero pharmaceutical funding
• 276 donors raised $23,024 in the Fund the Buzz spring campaign – thank you!