July 2025: This Month in Huntington’s Disease Research

This month, Huntington’s disease (HD) research offered powerful insights into how the brain changes over time, and how we might slow or track that progression. From using brain scans, smartphone tests, and even sleep patterns to detect early changes, to exploring new treatment angles like glial cell support, gene editing, and energy repair, scientists are uncovering new ways to fight HD at every stage. Even with the recent regulatory rejection of Prilenia’s pridopidine, studies from this month bring real hope that earlier detection, better monitoring, and smarter treatments may all soon be within reach.

Peeking at huntingtin and learning from a PET study

Researchers recently tested a new brain scanning tool called a PET imaging tracer, basically a tiny molecule that “lights up” when it sticks to the harmful huntingtin protein, which causes HD. By tracking this glow in brain scans, scientists hoped to see how much of the harmful protein builds up in people with HD. While the tracer was safe and didn’t cause side effects, it was a little too “sticky,” attaching to places it shouldn’t, kind of like glitter getting everywhere, which made the results harder to interpret.

Even though this particular tracer didn’t produce the results they hoped for, the study taught scientists a lot about how to design better ones. They found that comparing brain regions to the cerebellum (a part of the brain that’s usually spared in HD) helped reveal some meaningful patterns, and that spacing scans a week apart gave more reliable results than doing them back-to-back. For HD families, the big takeaway is this: scientists are getting closer to creating a tool that can track the huntingtin protein in real time, which could one day help monitor how well huntingtin-lowering treatments might be working.

Energy off balance: How Huntington’s disease influences the cell’s powerhouse

Scientists used tiny 3D brain models made from HD stem cells to study how the disease affects early brain development. They noticed that even before brain cells were fully formed, something was off, especially in the way cells made and used energy. A key energy gene called CHCHD2 wasn’t working well, which led to stressed-out mitochondria, the parts of the cell that act like power plants, supplying all the energy.

This matters because if brain cells can’t manage energy properly from the very beginning, they may not grow and develop the way they should, which could make them more likely to break down later. But the exciting part was that the researchers found that boosting the CHCHD2 energy gene seemed to fix the problem in these 3D mini-brains, pointing to a new way scientists might protect brain cells early in the disease.

Simon Says Stop: What a Children’s Game Can Teach Us About Early Huntington’s Disease

Scientists turned the childhood game “Simon Says” into a grown‑up test to see how early HD impacts attention and impulse control. People with early‑stage HD played a computer version: shapes flashed on the left or right and they had to press a button based on colour, not location. Tiny sensors on their thumbs detected even the smallest of muscle twitches, sometimes before a person could stop themselves. It turns out, those with early HD weren’t overly impulsive, but they did take longer to react and had trouble paying attention.

This work suggests that early HD doesn’t seem to make people act on impulse, but it does slow down their thinking and makes it harder to stay focused. Spotting these subtle changes could help doctors recognize HD sooner and guide better support strategies. Most importantly, for families dealing with HD, the study is hopeful because it shows that the brain can still control impulses and that early interventions, like therapies or exercises targeting attention, could help people stay more “in the game.”

This month, Huntington’s disease (HD) research offered powerful insights into how the brain changes over time, and how we might slow or track that progression.

Unsung Heroes: Could Glial Cells Treat Huntington’s Disease?

Scientists tested whether healthy human glial cells, the brain’s support crew, could help repair damage from HD. They transplanted glial progenitor cells into the brains of adult mice that model HD. The results were impressive – treated mice seemed to move better, remember more, live longer, and their neurons seemed to behave more like healthy ones.

This work suggests that by boosting the cells around neurons, we may be able to support and improve neuron function, even after symptoms have started. These “helper” cells might release repair signals or improve the brain environment, giving neurons a much-needed boost. It’s early days, but this type of research opens an exciting new potential route harnessing glial cells to heal the brain and using teamwork to fight HD.

Cracking the Case: How a Smartphone “Detective” is Helping Track Huntington’s Disease Progression

Scientists have created a new tool called the HD Digital Motor Score (HDDMS) that turns a smartphone into a “detective” for tracking HD progression. By using simple phone-based tests, like tapping, walking, balancing, and measuring involuntary movements, data is collected right from home. The HDDMS proved to be about twice as sensitive as traditional clinic tests, which means it could spot subtle changes in movement earlier and more reliably.

This could be a breakthrough because implementing the HDDMS would mean fewer clinic visits, smaller and faster clinical trials, and better tools to see if treatments are working, all without leaving your house. For HD families, that’s huge. It’s like having a superpowered magnifying glass in your pocket, potentially helping doctors and researchers catch disease progression sooner and tailor care more precisely.

Stopping the Genetic Snowball: How a simple genetic interruption slows Huntington’s disease

HD is caused by a repeating stretch of the genetic letters C-A-G that gets bigger over time, like a snowball rolling downhill. Scientists used a modified version of CRISPR, a powerful gene-editing tool, to insert a small genetic change in this repeat sequence. In cells and mice, this simple interruption appeared to slow the dangerous expansion and protect brain cells from damage.

This approach tackles one of the root causes of HD, not just the symptoms. By stopping the genetic snowball from gaining speed, this strategy could lead to long-lasting, effective treatments. It’s still too early to know for sure if this approach will work, but this gives real hope that slowing or even halting disease progression may be possible.

When the Brain’s Orchestra Falls Out of Tune: A New Map of Huntington’s Disease Progression

Scientists used a powerful brain imaging tool to map how HD changes the brain’s communication networks over time, and the results look a lot like a symphony falling apart in three acts. In the earliest stages, the brain actually becomes too connected. The team found that different regions talk over each other, like an orchestra playing too loud and out of sync. This “hyperconnectivity” seems to show up decades before symptoms and may be the brain’s way of trying to compensate for early damage.

As HD progresses, those connections unravel. The disease seems to spread along brain circuits, like a bad note jumping from section to section. Eventually, most of the brain’s communication seems to quiet down dramatically, leading to widespread disconnection. Each stage appears to be driven by different biological processes, from early chemical signaling issues to later energy and genetic breakdowns. The big takeaway is that HD doesn’t follow a straight line, it unfolds in stages, and knowing when and how the brain’s “music” starts to falter could help doctors time future treatments more precisely.

Together, these studies bring real hope that earlier detection, better monitoring, and smarter treatments may all soon be within reach.

Pridopidine Hits a Roadblock: EMA Says No to Approval for Huntington’s Disease Treatment

On July 25, 2025, Prilenia and its partner Ferrer received confirmation that the European Medicines Agency (EMA) has rejected their marketing authorization application for pridopidine as a treatment for HD in Europe. The decision aligns with earlier clinical trial outcomes showing that while pridopidine was generally safe and well tolerated, it failed to meet its primary endpoints in key trials, including the most recent PROOF‑HD trial. Although subgroup analyses hinted at modest benefits in Total Functional Capacity (TFC) among participants not on dopamine-affecting medications, those signals were not deemed robust enough to support approval.

Despite this setback, Prilenia and Ferrer have signaled their continued commitment to developing pridopidine, not only for HD but also for ALS. They plan to initiate a new global registrational study, aiming to further evaluate the drug’s clinical benefits across functional, cognitive, and motor domains. While a regulatory refusal represents a significant disappointment for HD families, the broader landscape of HD research remains dynamic and hopeful in 2025 with good news abounding and more trial news expected before the end of the year.

When the Brain’s Clock Breaks: Sleep Disruption and Circadian Chaos in Huntington’s Disease

A 12-year study followed people with the HD gene to see how their sleep changed over time and the results were eye-opening. Before symptoms even appeared, their sleep became unstable, like a broken clock that couldn’t keep time. Closer to disease onset, many had trouble staying asleep through the night. These sleep problems were tied to slower thinking, mood issues, and signs of nerve damage in the brain.

This study suggests that sleep may not just be a symptom of HD, it might play a role in how the disease progresses. Tracking sleep could help spot early warning signs years before symptoms begin, and improving sleep might even help protect brain health. For HD families, the message is clear – sleep is powerful, and it could become part of future strategies to slow or better manage HD.