Huntington’s Disease Clinical Research Congress 2025 – Day 1

This month, HDBuzz is attending the first Huntington’s Disease (HD) Clinical Research Congress in Nashville, Tennessee. Gathered at this meeting are hundreds of scientists, doctors, and industry representatives who have come together to talk about HD clinical research and care. This conference has been organized by the Huntington Study Group (HSG) and CHDI Foundation, big players in the HD space in basic and clinical research.

Day 1 of this meeting is the HD Community Research Day, where speakers will be talking about topics relevant to families. Let’s get into it. 

Demystifying Clinical Trials Part 1: What Do I Need to Know?

The first session was an interview style panel intended to demystify clinical trials and explain elements of a study like protocols, endpoints, the experience of participation, and what questions to ask. Dr. Arik Johnson, Chief Mission Officer at HDSA, spoke with Dr. W. Alexander Dalrymple, a neurologist at UVA, Dr. Daniel Claassen, CEO of HSG, and Frances Saldana, an HD advocate and President Emeritus of HDCare. 

Dr. Claassen explained that the goal of a clinical trial is to test whether a new drug for HD actually works. Many people approach these studies wondering how they can access the therapy, but Dr. Claassen reminds us that a clinical trial is an experiment first and foremost. 

Dr. Dalrymple then defined what a clinical trial protocol is – essentially a detailed plan for how a trial will proceed. It contains the background on the science behind the drug (also called preclinical data), the types of tests that will be done to see whether symptoms worsen or stay the same, and the schedule of visits from screening through the end of the trial. Clinical trial protocols lay out a very detailed roadmap of everything that will happen in the trial, including a plan for timed “checkpoints” where the data will be examined to make sure testing remains safe to continue. 

Next, Dr. Claassen went on to explain clinical trial endpoints: measurements made to determine how HD is progressing. Examples are the kinds of tests you might have when you visit your HD provider, assessments of movement, mood, and thinking. Through an interactive Q&A, both participants and speakers have emphasized the importance of sharing with providers what HD symptoms are occurring, and which feel most important to capture. 

Dr. Claassen then spoke about a couple of different ways that clinical approval can be attained faster. For example, Orphan Drug Status from the FDA allows for a more streamlined process of regulatory review, when a drug is intended to treat a rare disorder, like HD. 

All of the panelists reiterated that a clinical trial is a major commitment, and having a good understanding of exactly what you’ll be going through is an important part of making choices about participation. 

Demystifying Clinical Research Part 2: The Clinical Research Process

Next, Lisa Hale, Director of Patient Engagement at Teva Pharmaceuticals, and UVA Neurologist Dr. Dalrymple shared more about possible partnerships between families and industry in the clinical research process. 

Lisa began by explaining the difference between an observational trial, one that simply gathers information by measuring aspects of HD, versus a clinical trial, which tests whether an intervention like a drug or device is safe and effective. She highlighted the importance of diversity in clinical research, and some of the reasons that people take part in research – hope, access, and the desire to make a difference. 

Following this, Lisa laid out the timeline for clinical research, from discovery and development in a lab, through preclinical research on animal models, to the three phases of human testing, followed by approval. All along the later stages there is input from regulatory agencies that ultimately are responsible for whether a drug is approved for use by patients or not. 

A Phase 1 trial is about safety, Phase 2 side effects and how the drug works inside the body, and Phase 3 is a larger study to look at effectiveness in a larger population. The lesser discussed Phase 4 trials can take place following the approval of a drug, to make sure that the drug remains safe and effective, when it is given in the real-world context of prescriptions in clinic. 

Lisa reminded the audience that the reality is that about 9 out of 10 medications being tested in clinical trials don’t get approved. About half don’t work as hoped, about 3 in 10 have unmanageable side effects, and about 1 in 10 are difficult to take to the finish line for other reasons, sometimes financial.  

Dr. Dalrymple talked about the importance of a “control group,” or “placebo group,” a set of participants who do not receive a drug, so that they can be compared to those who do. He explains that participants are usually assigned randomly to get the drug or not, even in a rare disease like HD. In some cases all participants may receive the experimental treatment, and a separate observational group (like Enroll-HD participants) is used as the control. 

9 out of 10 medications being tested in clinical trials don’t get approved

The speakers wrapped up with big thanks to all clinical trial participants for their bravery and selflessness – it’s a big decision, and a big commitment! 

Informed Consent: Beyond the Fine Print and Into the Experience

Next we heard from McKenzie Luxmore and Danielle Buchanan from HSG, who talked about the process of consenting to a trial. They wanted to explain to the audience what these consent forms are and why they are so long and convoluted! 

Informed consent forms used in observational and interventional research participation explain the purpose of the study, what it entails, risks, known side effects, confidentiality, and contacts for questions. McKenzie broke down all the different types of terms that can go into a trial’s title, including phase, blinding, randomization, multicenter, placebo control, and longitudinal or cross sectional. Our glossary can help if you need a refresher! 

Next, she talked about what the forms tell a potential participant about a trial; the purpose, background, who is being tested, activities and visits, how long the trial is, what options the person has if they don’t participate, and what happens if someone is hurt during a trial, among other items! McKenzie reminded the audience that signing an informed consent form means that you have read the forms, understand them to the best of your ability, and have had the chance to ask questions, and agree to participate in the trial. 

Danielle encouraged folks to take time in the consent process, by requesting a copy of the form beforehand, carefully reading and discussing with loved ones, and asking the study team any questions. Then it can be signed, and it’s good to hold onto a copy for reference. She recommended that people focus on the schedule of events, and how comfortable they feel with the procedures and the risks. After signing, it’s a good idea to keep on hand the research team’s contacts, and any info about medications that are not allowed during the study. 

People with lived experience of Huntington’s disease are the real experts

These documents can be very long and complex! While a lot of the legal language must remain, sometimes companies assemble committees of family members for input on how to make the process smoother and more understandable. The speakers reminded everyone that they should expect the research team to help them understand anything they sign, and that it’s important to advocate for oneself when agreeing to participate in a trial! 

The FDA and You: Making Your Voice Heard

The next speaker was Phyllis Foxforth, Senior Manager of Advocacy at HDSA, who emphasized that people with lived experience of Huntington’s disease are the real experts, and will speak about how they can partner with clinicians and researchers to drive improvements in access and care. 

Phyllis believes that HD community members have an opportunity and a responsibility to tell medical product developers and regulators what is challenging about HD and what is most important to them. Regulators like the FDA have different types of engagement programs to get community feedback. 

The HDSA recently organized a Voice of the Patient survey and a Patient Focused Drug Development meeting with the FDA in order to engage with regulators about what’s important to people with HD. 

A Day in the Life: Research Visits from Start to Finish

The afternoon session focussed on what’s happening now and next in HD research. First, in a brief session, Danielle Buchanan, a clinical project manager at HSG, and Dr. Katherine McDonell, Assistant Professor of Neurology at Vanderbilt University Medical Center, explained what happens during a research visit for a clinical trial.

Visits are typically made up of different types of study measures, including surveys and thinking tasks, tablet and computer tasks, sample collection like blood, saliva, or CSF, movement tasks, brain MRI, and EEG. The speakers stressed that the research team, from coordinators to clinicians, is there to help folks navigate all the steps of the trial, as well as to support family members and study partners. 

Huntington’s Research Today and Tomorrow: A 5-Year Outlook

Next we will heard from Victor Sung from UAB, who will tell us all about his 5 year outlook on what’s coming in the HD clinical trial pipeline. Victor runs a large HD clinic at the University of Alabama. He notes that following the recent uniQure news his clinic has received more than 50 calls a day from people wanting to learn more. He’s excited about what’s next after this landmark study. 

Victor laid the groundwork for his talk by explaining that there are multiple approaches to HD research, including lowering the amount of huntingtin protein in brain cells, and preventing the expansion of CAG repeats. His takeaway was “the more the merrier!” The field welcomes all the players in the game who are looking for ways to slow down HD and to address the symptoms. He believes that one day there will be an “HD cocktail” of multiple options in different phases of progression. 

This is a historic moment because it’s the first time a drug for HD has moved the needle on disease progression

Dr. Sung spent some time getting into the uniQure announcement which we covered in late September. The most important graph shows that people who received AMT-130 progressed more slowly 3 years after the initial surgery, based on how much their scores on thinking and movement tests changed over time. 

This is a historic moment because it’s the first time a drug for HD has moved the needle on disease progression, but the data is nuanced. AMT-130 is not an approved or available treatment, there are more regulatory steps to go, and there are many future conversations to be had about access.  Victor noted that there are many more drugs on the way that are exploring other drivers of HD and applauded HD research participants for rising to meet the great challenge of testing experimental therapies. 

Perspectives on Research: A Participant Panel Discussion

In this next section of the day, participants took the mic. A panel of folks from the HD community shared what it was like for them to join trials, why they decided to participate in HD research and how the experience could be improved. 

The panelists shared about the family and community members who inspired them, their genetic testing journeys, and their desire to do something to feel motivated and to benefit the next generation of people with HD. 

Challenges they highlighted include participating in research while holding down jobs and caring for family members or children, and navigating the logistics of observational research visits, especially out-of-pocket expenses and reimbursement. 

The panelists note that the care teams at resources at various clinics can make a huge difference as far as the experience goes, and that logistics and procedures get easier the more you participate. 

Ask the HD Experts Anything!

The final session to wrap up the Community Research Day is one of our favourites – “Ask the Experts.” This Q&A with HD clinicians and scientists allows audience members to ask anything they want about HD research, drug discovery and clinical trials. 

HDBuzz also runs these type of sessions with many of our partner organisations so look out for our next one if you have any questions. You can also contact us any time with your queries or comments. 

More updates to come

That was it for Day 1 – thanks for reading! Tune back in for our coverage of Days 2 and 3.