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 (HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15). Let’s get into what we learned this month!

Themes That Unified the Month

The huntingtin proteinhuntingtin protein The protein produced by the HD gene.: not just a target, but a whole ecosystem

Three articles this month examined HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 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 HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 for disposal, disease gets dramatically worse. And the siRNA study showed that targeting the shorter, more toxic HTT1a fragment outperforms targeting full-length HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15. Together, this work suggests that the form of HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 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a new path through the UK’s MHRA after a complicated FDA interaction, while pridopidine’s European application, withdrawn six months ago, quietly closed that chapter for now.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 siRNAsiRNA A way of silencing genes using specially designed molecules of RNA – like DNA but made of only a single strand – that target the message molecules in cells and tell them not to make a certain protein (a molecular eraser that prevents specific proteins from being made), researchers injected either treatment into HD mice. Both reduced protein in the hippocampushippocampus the seahorse-shaped part of the brain that's crucial for memory, 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 HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15-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 HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 can no longer be tagged. The answer is that things get considerably worse. 

Mice that couldn’t ubiquitin-tag their toxic HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 had larger protein clumps, more brain inflammationinflammation Activation of the immune system, thought to be involved in the HD disease process, and faster motor symptom progression. The encouraging flip side is that if boosting the ubiquitin system speeds up HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 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 HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 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 neuronsneuron Brain cells that store and transmit information. 

Normally, the blood-brain barrierblood-brain barrier A natural barrier, made from reinforcements to blood vessels, that prevents many chemicals from getting into the brain from the bloodstream keeps these cells out. But in HD pigs, microgliamicroglia the brain's immune cells (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 neuronneuron Brain cells that store and transmit information 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 Trialclinical trial Very carefully planned experiments designed to answer specific questions about how a drug affects human beings 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 HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 by rerouting its RNARNA the chemical, similar to DNA, that makes up the 'message' molecules that cells use as working copies of genes, when manufacturing proteins. 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 cohortcohort a group of participants in a clinical research study from ENROLL-HD; the 5 mg dose showed 28% slowing. That dose-dependent pattern is exactly what you’d hope to see. NfLNfL biomarker of brain health, a marker of nerve cell damage, also remained below baseline at 24 months for both doses. This is meaningful because NfLNfL biomarker of brain health 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 HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 protein levels, full Stage 3 data, and brain MRImagnetic resonance A technique using powerful magnetic fields to produce detailed images of the brain in living humans and animals results, expected at a scientific meeting later this year. 

Novartis’s Phase 3 INVEST-HD trial is now enrolling people with 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 = 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 siRNAsiRNA A way of silencing genes using specially designed molecules of RNA – like DNA but made of only a single strand – that target the message molecules in cells and tell them not to make a certain protein study found that targeting HTT1a reduced toxic protein clumping and corrected gene activity changes more effectively than targeting full-length HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 and that earlier treatment worked better
• When HD mice couldn’t ubiquitin-tag toxic HTTHTT one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15 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 microgliamicroglia the brain's immune cells and blocking CCL8 reduced T cell entry and worsened neuronneuron Brain cells that store and transmit information 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 NfLNfL biomarker of brain health 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