March 2026: This Month in Huntington’s Disease Research

March was a big month for the HD community. Regulatory developments dominated the headlines, from disappointing regulatory news about AMT-130 to encouraging steps forward for SKY-0515. In the lab, research on 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. continues to gather momentum, with new insights from human neuronsneuron Brain cells that store and transmit information. HDBuzz was also front and center at the annual CHDI therapeuticstherapeutics treatments conference, providing a full sweep of where the science stands. The month closed with Gratitude Day, and two pieces that reminded us what this community is, and what it is made of.

Clinical Trialclinical trial Very carefully planned experiments designed to answer specific questions about how a drug affects human beings Updates

The road ahead for uniQure: FDA says more data needed for AMT-130

Some of the biggest news of the month came on March 2nd, when uniQure relayed communications from the U.S. Federal Drug Administration (FDA). The FDA does not believe  that uniQure’s current Phase 1/2 data are sufficient to currently support U.S.-based accelerated approval of AMT-130, a huntingtin-lowering gene therapy delivered via brain surgery. The FDA disagreed with the external control group uniQure used to benchmark the drug’s effectiveness and has strongly recommended conducting a new randomized, double-blind trial with a sham-surgery control arm.

This is genuinely disappointing news for families who have been closely following AMT-130’s progress and hoping for faster access to a drug designed to treat HD. A sham-controlled surgical study raises real practical and ethical challenges, and taking part in such a trial would likely prevent participants from accessing other disease-modifying drugs advancing through trials in parallel.

At the same time, it’s worth remembering what remains true: the Phase 1/2 data showed a promising safety profile and suggested that huntingtin lowering may slow progression in a small group of people. That data doesn’t change. Discussions between uniQure and the FDA are ongoing, with a Type B meeting planned for the second quarter of 2026 in which they will work through Phase 3 design options. uniQure is also advancing conversations with European regulators in parallel.

Australia opens the door for SKY-0515

On March 3rd, better news arrived from the other side of the world. Skyhawk Therapeuticstherapeutics treatments shared that Australia’s Therapeutic Goods Administration (TGA) determined that SKY-0515, a once-daily oral huntingtin-lowering pill, is eligible for Australia’s provisional approval pathway. Skyhawk submitted its formal application the same day.

SKY-0515 is a splice modulator, meaning it changes how cells process the genetic messages used to make huntingtin, reducing the amount of protein that gets made. In early trials, a low 9 mg dose lowered huntingtin levels by around 70%, a result the field hadn’t seen before from a pill. There’s also some evidence it may lower PMS1, a modifier of 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., though that story is still developing.

Provisional approval, if granted, would allow SKY-0515 to be prescribed in Australia before full Phase 3 results are in. Importantly, the ongoing FALCON-HD trial is designed as a randomized, placeboplacebo A placebo is a dummy medicine containing no active ingredients. The placebo effect is a psychological effect that causes people to feel better even if they’re taking a pill that doesn’t work.-controlled study, which stands in favorable contrast to the design issues raised around AMT-130. This is a regulatory step, not an approval, but it’s a meaningful one for a community where time matters.

Vico’s trial adds twice-yearly dosing arm, clears path to the U.S.

Also on March 2nd, Vico Therapeuticstherapeutics treatments announced a new fourth arm of their Phase 1/2a trial of VO659, testing just two doses per year rather than the once-monthly schedule used in earlier arms. VO659 is a huntingtin-lowering drug delivered by spinal injection that targets the CAG repeatCAG repeat The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD itself, making it potentially applicable to multiple repeat expansion diseases. To test this, it’s being trialed for HD, SCA1, and SCA3 simultaneously.

The move to less frequent dosing is likely aimed at improving the safety profile: a prior update revealed that several participants had experienced radiculitis, a painful nerve inflammationinflammation Activation of the immune system, thought to be involved in the HD disease process, at higher dose frequencies. Although the pain had already resolved for 3 of the 4 people who reported it, it’s important for companies to adapt trial protocols based on potentially serious side effects. Vico also announced FDA clearance to begin U.S.-based trials for VO659 later this year, expanding access beyond the European sites where the trial has run so far.

CHDI HD Therapeuticstherapeutics treatments Conference 2026

In late February, ~450 HD researchers gathered in Palm Springs for the 21st annual HD Therapeutics Conference, hosted by the CHDI Foundation. The HDBuzz team covered three full days of science, live from the front row.

The conference spanned the full breadth of HD research: the molecular biology of the huntingtin proteinhuntingtin protein The protein produced by the HD gene., the genetics of 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., and an emerging pipeline of drugs designed to slow CAG repeatCAG repeat The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD growth. Academic labs and early-stage companies alike, including Harness Therapeuticstherapeutics treatments, Latus Bio, and Rgenta Therapeuticstherapeutics treatments, shared preclinical data targeting the mismatch repair machinery as a route to slowing expansion. Later sessions brought in cutting-edge tools, like single-molecule imaging of DNA repair, mini-brain models complete with blood vessels, and a frank look at what clinical trialclinical trial Very carefully planned experiments designed to answer specific questions about how a drug affects human beings design will need to look like to actually get drugs across the regulatory finish line.

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. was the dominantdominant A genetic condition that only requires one copy of a mutation to occur through-line of the meeting, no longer a side story, but central to how the field is thinking about HD. Full coverage of Day 1, Day 2, and Day 3 are available on HDBuzz.

Understanding HD Biology

Turning down mismatch repair genes slows Huntington’s repeat growth in human neuronsneuron Brain cells that store and transmit information

We know from human genetics that DNA repair genes influence how quickly CAG repeats expand over time, and that slowing that expansion could potentially delay the onset of HD. 

A new study put this to the test in human neuronsneuron Brain cells that store and transmit information created from a person with HD. By carefully dialing down specific DNA repair genes, the team slowed CAG expansion by up to 69%. This confirmed in human brain cells in a dish what had previously been seen mainly in mice. 

Safety considerations and additional work remain, but the study helps to narrow down which genes have the most potential as anti-expansion therapies.

Two Heads Are Better Than One: Combined physical and music therapy for late-stage HD

A new study published in the Journal of Interprofessional Education & Practice explored what happens when a physical therapist and music therapist work together with people in late-stage HD. The short answer: it helps, but the details matter. 

Simple, implicit cues worked far better than complex ones. A steady drumbeat improved movement control and reduced choreachorea Involuntary, irregular ‘fidgety’ movements that are common in HD more effectively than guitar accompaniment, and brief verbal cues outperformed elaborate instructions. For people in late-stage HD, cognitive load is a real constraint, and keeping external triggers simple helps the body respond.

The study is small with only 10 participants, but is the first to examine this specific collaborative care model in late-stage HD, and its findings have immediate practical relevance for care settings and caregiver training.

Gratitude Day 2026

Each year on March 23rd (the date of the discovery of the gene in 1993), the HD community marks Gratitude Day, a moment to honor the families, researchers, and advocates whose contributions help us advance to an HD-free future. This year, HDBuzz published two pieces honoring our community.

The Girl at the End of the World tells the story of Barranquitas, Venezuela, the lakeside community where decades of research partnerships laid the genetic groundwork for everything that followed. This story was centered through the lens of a 10-year-old girl named Jade, visited by occupational therapist Alex Fisher just weeks before she died. It is a piece about gratitude, but also about urgency and the human cost of the distance between discovery and treatment.

Why Huntington’s Disease May Be Neuroscience’s Best Investment is a guest piece by Roy Maimon, PhD, Assistant Professor of Biomedical Engineering at NYU. Writing from the perspective of a researcher who came to HD science and found both a compelling scientific problem and a remarkable community, Roy argues that HD’s genetic clarity, predictable course, and deeply engaged patient and advocacy ecosystem make it one of the highest-leverage investments in all of neuroscience.

Together, the two pieces bookend Gratitude Day: one looks back at the foundations of research into HD genetics, and one looks forward at its promise.

Looking Ahead

March was a month that asked a lot of the HD community emotionally, particularly around AMT-130, while also offering real affirmation of forward momentum. We saw a promising regulatory step for SKY-0515, new human cell data on 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., and the collective energy of a full three days of conference science. 

The field is not standing still. The path forward for any individual drug may shift, but the scientific infrastructure underneath it, built with better models, clearer biomarkers, and deeper mechanistic understanding, keeps getting stronger.

As the community processes the AMT-130 news and watches regulatory conversations develop on multiple fronts, HDBuzz will continue to cover every significant development, in the plain language the HD community deserves.

Summary

• The FDA communicated to uniQure that current Phase 1/2 data are not sufficient to support accelerated approval of AMT-130 in the U.S., saying a new randomized, sham-controlled trial may be required. Discussions with the FDA and European regulators are ongoing.
• Australia’s TGA determined that SKY-0515, Skyhawk’s once-daily oral huntingtin-lowering pill, is eligible for the provisional (accelerated) approval pathway. A full review is underway.
• Vico Therapeuticstherapeutics treatments launched a new twice-yearly dosing arm of the VO659 ASOASOs A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene trial and received FDA clearance to begin U.S. trials later this year.
• The 21st annual CHDI HD Therapeuticstherapeutics treatments Conference brought together ~450 researchers across three days in Palm Springs, with a strong focus on 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. biology and an emerging pipeline of anti-expansion drugs.
• A study in human HD neuronsneuron Brain cells that store and transmit information showed that partially dialing down mismatch repair genes may slow CAG expansion by up to 69%, supporting anti-expansion as a therapeutic strategy.
• A small study of combined physical and music therapy in late-stage HD found that simple, implicit cues like a drum beat led to better movement control than complex instructions or melodic accompaniment.
• Gratitude Day 2026 was marked with two pieces: a tribute to the Venezuelan families whose generosity built HD science, and a guest article from Roy Maimon arguing that HD is neuroscience’s best investment.