June 2025: This Month in Huntington’s Disease Research

Welcome to your June roundup of the latest and greatest Huntington’s disease (HD) research, served up fresh and easy to digest! This month, we’ve got gene therapies revving up, brain wiring revealing surprising detours, and molecular firefighters missing in action. From emotional rollercoasters inside the brain to decoding irritability storms, June’s science brings us closer to understanding HD’s many twists and turns. Buckle up for a fun ride through the newest discoveries lighting the way toward better treatments and brighter hope.

The 2025 HDBuzz Prize for Young Science Writers Is Open!

The 2025 HDBuzz Prize for Young Science Writers officially opened this month! This year the competition is supported by the Hereditary Disease Foundation (HDF). We’re inviting early-career researchers, such as PhD students, postdocs, early stage investigators, and clinicians, who are actively involved in Huntington’s disease (HD) research to write an entry in accessible, engaging language. Beyond enhancing communication skills and bolstering CVs, winners will see their work published and syndicated globally, and receive a prize of US $200.

To enter, applicants should write a ~200‑word pitch explaining their proposed topic and its importance to HD families. Selected pitches will be invited to submit full articles. The deadline for pitches is July 1, 2025, at 5 pm ET. Winning submissions will be announced in autumn 2025, published in multiple languages, and help diversify the perspectives featured on HDBuzz. If interested, get cracking!

Full Steam Ahead: uniQure’s On Track With Hope for Accelerated Approval of Huntington’s Disease Drug

On June 2, 2025, uniQure shared that they’re aligned with the FDA about moving forward with their HTT-lowering gene therapy, AMT‑130. If the next round of results from their ongoing trial continues to meet endpoints and show positive results, an additional clinical trial wouldn’t be needed for a shot at accelerated approval. 

They’ve hashed out manufacturing plans (so they can make enough for folks should things work), agreed on statistical analysis plans around the cUHDRS and NfL biomarkers, and decided to compare AMT‑130 patients to the massive Enroll‑HD dataset instead of a traditional placebo group. All of this keeps uniQure on track to potentially submit an FDA Biologics Licensing Application (BLA) in Q1 2026 — fingers crossed! 

Looking ahead, uniQure is set to show off 3‑year follow-up data by the end of September 2025, and then regroup with the FDA in Q4 2025 to set sights on that BLA filing. If all goes to plan, this could mean the first-ever gene therapy approved for Huntington’s disease. But, full disclosure: the whistle hasn’t blown yet. Everything hinges on uniQure having strong data through Q3 2025. Here’s hoping that data delivers the signal we all want!

If all goes to plan, this could mean the first-ever gene therapy approved for Huntington’s disease. But, full disclosure: the whistle hasn’t blown yet. Everything hinges on uniQure having strong data through Q3 2025.

One Disease, Many Paths: How Brain Wiring Shapes Huntington’s Symptoms

HD doesn’t follow just one path. It rewires the brain in different ways depending on the symptoms. A new brain imaging study found that people with more movement and thinking issues reroute activity through backup circuits, like the brain’s version of side streets after a highway closes. But folks with mood and behavior symptoms lose connections more broadly, especially between emotional hubs.

These findings help explain why HD looks different from person to person, and why care should be tailored to each brain’s unique “traffic pattern.” It’s a step toward more personalized treatment, guided by how the brain is wired, not just what symptoms show up.

Inside the Brain’s Theme Park: How Huntington’s Disease Disrupts the Emotion Coaster

In Brainland, the theme park inside your head, the “Emotion Coaster” takes you through loops of joy, sadness, and anger. But for folks with pre‑manifest HD, the ride starts sputtering early on, especially when spotting anger, sadness, and fear on people’s faces. It’s like the coaster’s brakes get stuck, making it tougher to read emotional cues. This can be jarring when the rest of the park (memory, movement) seems fine.

A group at Harvard and MGH used MRI scans to map this coaster’s traffic patterns and found the brain zones that power emotion radar aren’t lighting up the way they should. When the coaster loses steam, social misreads can snowball, causing worked-up conversations, awkward moments, or missed cues. But here’s the silver lining: noticing this early wobble could let caregivers give a heads up, like the ability to add emotional training wheels before the big rides go haywire. Early detection could mean smoother rides ahead.

When a Short Fuse Becomes a Storm: Understanding Irritability in Huntington’s Disease

Living with HD can feel like walking around with a tiny temper volcano inside. In a new study, researchers spoke with people both before and after HD symptoms show up to explore what irritability really feels like. It’s not just a mood swing — it erupts suddenly, over little things, and leaves both the person with HD and their loved ones in a storm of frustration, confusion, and emotional exhaustion.

But there’s hope behind the clouds. The team broke down what triggers these “irritability storms” (hunger, fatigue, chaos, stress) and how people cope, through things like taking a break, leaning on friends, tweaking routines, or even using medication to ease the pressure. A major takeaway is that irritability is a real symptom of HD, not just grumpiness, and recognizing it means we can offer targeted support to help manage it with more grace and understanding.

The latest volume of HD genetics research reveals new gems but also mysteries

Researchers have just dropped the newest edition of HD genetics studies, and it’s unearthed hidden treasures (and a few puzzles). They’ve uncovered fresh genetic “spelling quirks”, from rare interruption variants that change how the notorious CAG repeat behaves, to tiny DNA flags that shift symptom timing by over a decade. Plus, they’ve spotlighted epigenetic tweaks in gene regulation, which act like traffic lights malfunctioning and causing genetic chaos in brain cell development.

But that’s not all. These findings raise big, yet awesome questions: Which of these quirks are the true game-changers, and which are just background noise? It’s a bit like discovering secret side quests in an open-world game — you know there’s cool stuff to unlock, but you need the right strategy to access the boss fights. In short, genetics has tossed us fresh gems…and a few cliffhangers, too.

Spark Therapeutics (now part of Roche) just kicked off a new gene therapy trial for HD and the first patient has been dosed with their one-and-done treatment, RG6662 (aka SPK‑10001).

Spark ignited: first HD patient dosed in new Roche gene therapy trial

Spark Therapeutics (now part of Roche) just kicked off a new gene therapy trial for HD and the first patient has been dosed with their one-and-done treatment, RG6662 (aka SPK‑10001). This AAV-delivered therapy is designed to permanently dial down levels of both expanded and unexpanded huntingtin protein via brain surgery, aiming for a lasting therapeutic effect. It’s been a saga: from academic discovery, to biotech startup, to Roche’s acquisition, now culminating in this exciting first-in-human milestone.

The Phase 1 “Part A” trial in the U.S. will start slowly and safely, dosing up to eight people with early-stage HD aged 25–65, with careful monitoring and potential dose adjustments. Subsequent phases include placebo-controlled arms while ensuring everyone eventually gets the real therapy, followed by long-term safety and effectiveness checks. Spark and Roche are partnering closely with HD advocacy groups and the Huntington Study Group, showing serious community engagement and transparency — a spark ignited indeed!

Trouble on the Block: When the Neighborhood Loses Its Best Firefighter

Imagine your brain is a neighborhood, and neurons are the residents. Normally, when things go awry, like a fire breaking out, PKD1, the brain’s “molecular firefighter,” rushes in to save the day. But in HD, PKD1 is missing in action, leaving neurons vulnerable to damage. Without PKD1, neurons can’t handle the stress from overactive signals and toxic buildup, potentially contributing to their decline.

Researchers have discovered that PKD1 levels drop early in HD, particularly in the striatum, even though the genetic instructions to produce it are still present. This suggests that the body knows it needs the firefighter but isn’t producing it properly. Understanding why PKD1 goes missing could help scientists find ways to bolster the brain’s defenses and protect neurons from the damaging effects of HD.

That’s a wrap on June’s HD research highlights! Each study adds a new piece to the puzzle, helping us better understand the brain’s challenges around HD. With gene therapies advancing and fresh insights into symptoms and brain changes, the future looks brighter than ever. Stay curious, stay hopeful, and we’ll keep bringing you the science that matters.