Huntington's Disease Therapeutics Conference 2025 - Day 1 HDBuzz reported live updates on Bluesky from the 2025 HD Therapeutics Conference. Read on for coverage of Day 1. #CHDI2025

But if you're in a time crunch, you can always catch up on all the exciting science from #CHDI2025 in the HDBuzz summaries. 😉

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That’s all folks! We hope you enjoyed following along and learning about all of the super cool new HD research going on all over the world. #CHDI2025

She ended by stressing that sample collection and storage is critical for successful evaluation of biomarkers. This remains a high priority for CHDI as well as all researchers working on biomarker development. #CHDI2025

Hillary brought up some advantages of using somatic instability as a biomarker, but there are limitations too. We can’t measure expansions in the brain while people are alive and what we can measure in blood is very subtle. There is work to do before we can use this in clinical trials #CHDI2025

Now she’s switching gears to newer biomarkers in the HD space, PENK and PDYN, which may have potential as disease activity biomarkers. Right now they’re working on figuring out how they can robustly measure these two new biomarkers. #CHDI2025

Now she’s switching gears to newer biomarkers in the HD space, PENK and PDYN, which may have potential as disease activity biomarkers. Right now they’re working on figuring out how they can robustly measure these 2 new biomarkers. #CHDI2025

In looking at NfL data from both HD-Clarity and Enroll-HD, Hillary feels it could be used for selection of clinical trial participants and may be useful for clinical trial design. Having such a powerful biomarker with multiple uses would be a big advantage. #CHDI2025

Like others have shown, Hillary also sees an increase in NfL in CSF through HD disease stages with elevated levels seen very early, before symptoms are obvious. #CHDI2025

Now Hillary is moving on to the data she has looking at NfL as a biomarker. Levels of NfL in CSF seem to tally with the amount of neuronal damage caused by HD. Also, like expanded HTT, NfL levels in CSF are reproducible across visits for people in the HD-Clarity trial. #CHDI2025

However, a very important caveat is that expanded HTT levels don’t correlate with HD signs and symptoms. So there are clearly limitations with using this specific biomarker for measuring certain clinical changes associated with HD. #CHDI2025

She thinks blood levels of expanded HTT will make a good biomarker for intervention trials because distribution levels correlate with disease severity. This helps researchers stratify people with HD by disease stage just by looking at levels of expanded HTT that they have in their blood #CHDI2025

Hillary is sharing an experimental plan for looking at levels of biomarkers using samples from the HD-Clarity dataset. When they look at expanded HTT in CSF, the fluid that bathes the brain, they see good reproducibility across site visits. This is critical for a good biomarker! #CHDI2025

They’re not just asking these questions about new biomarkers, but also old biomarkers. Some of our oldest and currently most reliable biomarkers in HD research are expanded HTT and NfL. #CHDI2025

Just some of those questions are, how can we collect samples to optimize detection? How do we decide on the context of use for a biomarker? What sorts of statistical tests should we use for various approaches? #CHDI2025

These uses could be diagnosis, prognosis, safety or efficacy of drugs, as well as disease progression. Hillary and the team are working to answer various questions about how we can most logically apply biomarkers across all of the uses they have. #CHDI2025

The final talk of the conference is from Hilary Wilkinson from CHDI. She will be telling us about different types of CSF and blood-based biomarkers that are used in HD clinical research. Biomarkers can be used for LOTS of different things in HD research. #CHDI2025

During the Q&A portion, someone asked Peter when they think they’ll be ready for clinical trials for this approach that specifically targets the expanded copy. Peter said they’re planning to start trials for this approach by the end of this year. Stay tuned! #CHDI2025

One of their goals now is to identify the number of people across the globe that have this unique genetic signature and so might benefit from this new drug candidate. They’re also collecting geographic data to see exactly where in the world these people are. #CHDI2025

With the knowledge that this approach seems to work in mice, they turned back to their data from people from the GENERATION-HD1 trial. This lets them see exactly how many people have the unique genetic area on their expanded HTT gene that they want to target. #CHDI2025

They have already tested this new drug candidate in mouse models of HD and shown that their drug preserves regular huntingtin whilst lowering the expanded huntingtin. Great news! #CHDI2025

While this obviously means that, if successful, this specific drug wouldn’t work for 60% of people with HD, if this is successful Roche would certainly work to develop other iterations that *do* work for everyone with HD. This is very similar to what Wave Life Sciences are doing. #CHDI2025

The strategy Roche is using is to target a short region of the huntingtin gene that is only found in the expanded copy of the gene. The unique genetic area they have chosen is found in about 40% of people with HD. #CHDI2025

The strategy Roche is using is to target a short region of the huntingtin gene that is only found in the expanded copy of the gene. The unique genetic area they have chosen is found in about 40% of people with HD. #CHDI2025

For the penultimate talk of the day, we are hearing from Peter McColgan from Roche. If you are having deja vu, don’t panic, Peter did already give a talk on Day1 and is back again for Day3. He will tell us about Roche's approach for just lowering expanded huntingtin #CHDI2025

Manuela finishes by thanking the participants in this study, who went through so many brain scans! It is a huge commitment of time and energy, and a truly impactful contribution. #CHDI2025

This was just the findings from the PET imaging part of this study! #CHDI2025

This study has done a ton of work! The findings so far are very interesting. Some of these measures showed clear differences between the groups assessed whereas others were less obvious. This helps HD researchers know which brain features they need to pay attention to. #CHDI2025

One approach uses special tracer molecules that light up the brain when they stick on to certain markers. Many markers are known readouts of brain health. Seeing how much the brain lights up in different people at different stages of HD could help us understand how HD changes brain health #CHDI2025

They are relying on several different high tech ways of imaging the brain to paint a more thorough picture, which should help figure out some of the very subtle changes which happen in HD throughout the disease course. #CHDI2025

Studies like this can help us better understand the brain changes which happen during in HD in much more detail, as the same people are measured again and again over the 5 year timeframe #CHDI2025