May 2026: This Month in Huntington’s Disease Research

May was a month of clinical momentum and molecular depth. Long-term data from the votoplam trial continued to build confidence in that program, the AMT-130 story took a meaningful international turn, and three basic science articles gave us new ways to think about how the brain handles, and mishandles, toxic huntingtin (HTT). Let’s get into what we learned this month!

Themes That Unified the Month

The huntingtin protein: not just a target, but a whole ecosystem

Three articles this month examined HTT from different angles. The votoplam clinical data showed that lowering it may slow disease progression. The ubiquitin study showed that when the brain’s natural clean-up system can’t tag HTT for disposal, disease gets dramatically worse. And the siRNA study showed that targeting the shorter, more toxic HTT1a fragment outperforms targeting full-length HTT. Together, this work suggests that the form of HTT matters, and the rate at which the brain clears it matters too.

The regulatory landscape is actively reshaping

May brought two regulatory stories pointing in different directions. AMT-130 is pursuing a new path through the UK’s MHRA after a complicated FDA interaction, while pridopidine’s European application, withdrawn six months ago, quietly closed that chapter for now. Having accurate, complete information on both is exactly what HDBuzz exists to provide.

HD affects more than one person

For the second consecutive month, a care study reminded us that HD’s reach extends beyond the person with the gene. A Dutch study asked families and professional caregivers what “good care” actually looks like and found that the answer is more complicated than any checklist can capture.

Understanding HD Biology

Fixing the Recipe: Lowering a Slice of Huntingtin

A new study asked whether targeting full-length HTT or the shorter, more toxic HTT1a fragment more effectively reduces disease signs in HD mice. They found HTT1a is the more important target. Using siRNA (a molecular eraser that prevents specific proteins from being made), researchers injected either treatment into HD mice. Both reduced protein in the hippocampus, but only the HTT1a treatment meaningfully reduced toxic protein clumping and corrected disease-related gene activity changes. 

Critically, timing mattered. Mice treated early or twice fared significantly better than those treated later. This adds weight to the case that HTT-lowering therapies designed to target, or at least include, HTT1a may work better than those that don’t.

Tagging the Trash: Turnover of Toxic Huntingtin

Your cells have a clean-up crew that tags damaged proteins with a molecular sticky note called ubiquitin, marking them for disposal. A new study investigated what happens when toxic HTT can no longer be tagged. The answer is that things get considerably worse. 

Mice that couldn’t ubiquitin-tag their toxic HTT had larger protein clumps, more brain inflammation, and faster motor symptom progression. The encouraging flip side is that if boosting the ubiquitin system speeds up HTT clearance, it could be a therapeutic avenue. 

An already-approved drug called desonide has shown some ability to promote this tagging, and the study points toward testing whether adding more “junk labels” to toxic HTT could slow disease.

Intruders in the Brain: What a Pig Model Reveals about Immune Cells in HD

Mouse models can’t capture everything that happens in the human brain. A new study turned to a genetically engineered pig model of HD and found something mice couldn’t tell us about HD. The researchers found that cytotoxic T cells, which are the immune system’s trained killers, were invading the brain and clustering near neurons. 

Normally, the blood-brain barrier keeps these cells out. But in HD pigs, microglia (the brain’s resident immune cells) were releasing a signal called CCL8 that acted like an invitation, letting T cells in. 

When mouse brain cells were engineered to produce CCL8, T cells entered and worsened neuron loss. Blocking CCL8 reversed the effect. It’s an exciting potential therapeutic pathway, though much more work is needed to establish whether this operates in people.

Clinical Trial Updates

Two Years In: New Long-Term Extension Data from PIVOT-HD for Votoplam

New data from PTC Therapeutics give the first two-year look at participants in the long-term extension of PIVOT-HD, the Phase 2 trial of votoplam, which is the once-daily pill that lowers HTT by rerouting its RNA message for disposal. 

HD-ISS Stage 2 participants on the 10 mg dose showed 52% slowing of disease progression on the cUHDRS compared to a matched natural history cohort from ENROLL-HD; the 5 mg dose showed 28% slowing. That dose-dependent pattern is exactly what you’d hope to see. NfL, a marker of nerve cell damage, also remained below baseline at 24 months for both doses. This is meaningful because NfL typically rises over time as HD progresses. 

For Stage 3 participants, the picture remains incomplete: PTC described only “potential signals” and the subscale breakdown has not yet been reported. Some data is still outstanding, like 24-month HTT protein levels, full Stage 3 data, and brain MRI results, expected at a scientific meeting later this year. 

Novartis’s Phase 3 INVEST-HD trial is now enrolling people with TFC = 13 and early motor signs.

A Second Path: uniQure Plans Regulatory Filing for AMT-130 in the UK

On April 30, 2026, uniQure announced a successful Pre-Submission Meeting with the UK’s MHRA and plans to submit a formal Marketing Authorization Application in Q3 2026, based on three-year Phase 1/2 data showing approximately 75% slowing of disease progression at the high dose. 

This matters because the MHRA operates independently of the FDA, which earlier this year requested a new randomized, sham-controlled trial before moving AMT-130 forward on the regulatory path. Different agencies can, and do, reach different conclusions from the same data. 

Also notable is that Dr. Vinay Prasad, the CBER director who pushed back hardest on AMT-130, departed the FDA on April 30 and his position at the agency is currently open. 

Four-year AMT-130 data and a Type B FDA meeting on Phase 3 design are both expected in Q3 2026. We’ll be watching closely.

Pridopidine’s European Application: A Quiet Withdrawal

This month we reported that Prilenia withdrew its European Marketing Authorization Application for pridopidine (Nurzigma) on November 7, 2025. 

In July 2025, the EMA’s expert committee had recommended refusing approval, finding that neither the main PROOF-HD trial nor its subgroup analysis demonstrated effectiveness, and that pridopidine did not qualify for the conditional approval pathway. Prilenia requested re-examination, then withdrew before it concluded. 

People in ongoing trials or compassionate use programs are unaffected. The HD community deserves to know when regulatory processes conclude, in either direction, which is why we’re reporting it now.

Living with HD

The Great Care Conundrum: What “Good” Care Looks Like in Huntington’s Disease

A new study from the Netherlands brought together 22 family members and professional caregivers from three specialized HD nursing homes to ask: what does good care actually look like? Both groups agreed on the essentials, like skilled, continuous staffing; structure and predictability; attentiveness to nutrition and swallowing; and emotional care that treats residents as individuals. 

Families also highlighted how poorly supported the transition into residential care tends to be. The study surfaces a real gap in that there is still no consistent, agreed-upon definition of quality care in HD, and “specialist center” labels don’t always reflect daily reality. Future research needs to hear directly from people living with HD themselves.

From HDBuzz

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Summary

• A siRNA study found that targeting HTT1a reduced toxic protein clumping and corrected gene activity changes more effectively than targeting full-length HTT and that earlier treatment worked better
• When HD mice couldn’t ubiquitin-tag toxic HTT for disposal, disease progressed faster, suggesting that boosting the brain’s natural clean-up system could be therapeutic
• A pig model revealed cytotoxic T cells invading the HD brain via a CCL8 signal from microglia and blocking CCL8 reduced T cell entry and worsened neuron loss, representing a possible new therapeutic pathway, though still early
• New 24-month votoplam data showed 52% slowing of disease progression in HD-ISS Stage 2 participants on 10 mg, with NfL remaining below baseline; INVEST-HD is now enrolling
• uniQure plans to file for UK MHRA approval of AMT-130 in Q3 2026; US regulatory discussions and four-year data are both expected in Q3 2026
• Pridopidine’s European application was withdrawn in November 2025 following the EMA’s recommendation to refuse approval
• A Dutch study found that good HD care depends on skilled staffing, structure, emotional attunement, and a homelike environment, but consistent standards for quality care in HD are lacking