Lauren Holder is gene-positive and prodromal. Her happy-go-lucky father began displaying behavioral and cognitive issues that led to dark moods and self-harm when he was in his 40s. At 50, he was diagnosed with HD, and Lauren and her mother became his caretakers. Lauren later became his legal guardian, as well, until his passing in 2021 at the age of 62. When Lauren was 20, she decided to test.
Despite the fact that much of her life has been defined by HD, from early adulthood, Lauren has forged a path that comprises both a family of her own and a commitment to HD advocacy. This encompasses numerous initiatives, including podcasts (produced by Help4HD) and a new group whose mission is to speed up the “pace” of trials for people who are presymptomatic.
“In 2021, Roche halted their Generation HD-1 trial, which was devastating. Soon after, Seth Rotberg and BJ Viau came to me, expressing the sense of urgency that they felt and knew that I felt as well,” she said. “We put our heads together and asked, ‘How do we help research move forward? Where are the areas that we can help? Is it mostly regulatory hurdles? Is it more on the clinical side?’ In 2022, we did a patient listening session with the FDA to bring their attention to the benefits of trials for gene-positive people with presymptomatic or premanifest HD.”
This session sparked momentum to both ratchet up the voices pushing for these trials and broach obstacles in the regulatory process.
“That evolved into a little group called HD-PACE, and we are continuing to work with all stakeholders and try to figure out where we, as seasoned advocates, can help,” she said.
Shared Learning
One of the things HD-PACE does is reach beyond the HD silo to other communities, like ALS advocacy groups, to learn from their successes in being heard, overcoming red tape and accelerating trials. The ALS advocates have created a guidebook for the ALS community that serves as a model for a planned HD guidebook.
Although only 10% of ALS cases are genetic, there is overlap in the two research communities, as ALS scientists are probing presymptomatic disease in genetic cases, including studies on somatic expansion. Together, advocates in both disease communities held a think tank meeting with researchers, including Daniel Claassen, CEO of the Huntington Study Group and a long-time clinical investigator in HD research.
“We wanted to avoid reinventing the wheel and really gain from their experience so that we could be successful as well,” Lauren said. “The ALS people are so open to helping. When you realize that there’s a broader rare disease community behind you, it changes everything, because you now have resources and support you never thought you had.”
Lauren then collaborated with advocates from the ALS nonprofit, Legacy, speaking on panels addressing the FDA at the World Orphan Drug Congress in Boston. Their shared goal is to elevate the voice of the entire adult onset, autosomal dominant neurodegenerative disease community.
From there, she was able to connect with Cures Collective. Started primarily by an ALS organization, Cures Collective has brought together several rare neurodegenerative disease communities facing similar research and regulatory challenges.
“We are now keeping an eye on each other’s research and also asking, ‘Where is our overlap? How do we work together to bridge the gaps and to push where we need to go to open doors?’” Lauren said.
Synergy Through C-Path
The HD-PACE group also attends monthly meetings with C-Path, an FDA-created liaison with the rare disease communities, to facilitate a faster path to trial.
“Since ALS is well-established with C-Path,” Lauren said, “it’s giving us the template so that we don’t have to invent something and then correct it and correct it and correct it until we get it right.”
C-Path was established over a decade ago, but Lauren has felt a recent shift toward a more proactive approach for rare disease communities.
“I think it’s largely thanks to the ALS community and how loud they got,” she said. “They created a group called HD-RSC that brings together different stakeholders in the HD community. CHDI, Help4HD, HDSA and HDYO all have a seat at the table to figure out how to move forward in a productive way.”
Lauren was invited to speak with C-Path and the FDA at their September conference in Washington, D.C.
She cites identifying valid biomarkers as the biggest factor, currently, that can help accelerate clinical trials. However, she says more trials are relying on natural history as the control, with uniQure paving the way with their AMT-130 trials.
“This accelerated pathway they gained with the FDA will save a lot of time,” she said. “We were able to have a patient-focused drug development meeting last year because C-Path helped us speak directly with the FDA and say, ‘This is urgent. We need something in our community.’ And so they truly made that happen.”
HD Uncut
Strategic meetings and speaking opportunities are vital, but not all that is needed to accelerate the path toward slowing and stopping HD. Keeping the HD community educated and updated is also necessary to amplify HD family voices. Currently, Lauren has 160,000 worldwide listeners who tune in to her Help 4 HD-facilitated podcast, HD Uncut. Here, community members — including researchers, industry, and HD resource organizations — come on the show and talk, uncensored, about HD. She also has a global series featuring HD ambassadors sharing their work.
“There is also a support element, besides sharing the science,” Lauren said. “Having a strong community of others who are gene-positive or otherwise in HD families, has made such a huge difference for people with HD in this era. We are a close-knit community and when you have fear and need somebody to talk to who understands, you know that you have someone to call.”
Toward Early Support
To enable early HD trials, more gene-positive people need to be identified at an earlier stage. For Lauren, testing was not a hard decision.
“I was told I couldn’t participate in research, that there was no reason for me to test, because it wouldn’t benefit me at all. But I needed to test — for me. And I think the best thing that I have learned in the 20 years since is a mindset that I don’t have to be dying from HD, I can be living with HD. And my hope is always we can change to that mindset in the HD community — that we are not dealing with a death sentence, we are dealing with a disease we can learn to live with, while we come closer to finding disease-modifying treatments and things that will delay onset.”
She points out that this mindset fosters advocacy for earlier clinic visits, so that resources can be provided before movement disorders start.
“If they’re experiencing even the beginnings of these behavioral and cognitive symptoms, they can come and get a baseline. That’s the best thing I ever did for myself. When I started experiencing problems while working at the Alzheimer’s Association in 2022, I was able to go and get follow-up neurocognitive testing, and they could compare it to my baseline,” she said. “Let’s start early. Let’s get resources early on. And mental health resources are huge. We need that support. Our journey is going to be so much better if we go that way.”
That said, she adds a caveat:
“I am an advocate for testing in that it was the right decision for me. I would never, ever tell somebody that their decision is right or wrong, because you can’t know what that person is feeling, with the individual variables in their lives, faced with such a decision. But I do think that, as a whole, the decision is complicated by too many people being left with just the test results and a goodbye until symptoms start,” she said. “If there were resources available to presymptomatic people, if there were a plan for them, people might make a different decision.”
Mission-Driven, with Balance
At 19, when Lauren was just getting wind of her father’s changing behaviors, she married a nuclear engineer in the Navy, and today they share two children, now five and seven.
But outside of her home life, advocacy, speaking engagements and podcasts are her passion.
“I can’t imagine not doing it. I feel like it’s my way of coping with everything, by being able to provide a voice when others just can’t,” she said. “Sometimes when it’s all too much, I get a message from someone saying, ‘You have no idea how much it meant that you shared this and that you’re struggling with it,’ or ‘Thank you so much for taking my story to the FDA,’ and I know that even though this work is not easy, I wouldn’t change a thing.”
Perspective of a Trial Participant
Lauren has participated in observational studies, but also in stage 1 of an interventional trial (SURVEYOR) on dalzanemdor, a Sage Therapeutics drug that addressed cognitive symptoms of HD. She was part of their open label extension.
“SURVEYOR was halted last year because the data from the 12-week trial period didn’t show significant benefit. It was frustrating because, like a number of others, I felt that it helped me, at least initially,” Lauren said.
During the placebo-controlled, double-blinded portion of the trial, she went for testing every two weeks and then monthly for the open label extension.
She applauds the MedStar/Georgetown Center of Excellence that managed her participation.
“They were awesome, knew exactly what to do for somebody with HD, and made it easy for me,” she said. “Sage Therapeutics used a company to help with travel and reimbursement and things like that. A lot of this was taken care of up front, so that way, we didn’t have to deal with reimbursement. There was no way I would have been able
to do the clinical trial otherwise.”
At the same time, she cautions that the testing (in this case, brain testing) can be exhausting.
“It takes a lot more energy for somebody with HD to do these exercises, and when I needed to dedicate a full day to it, I crashed afterwards, so I just had to prepare for that. Fortunately, if I got tired at the clinical research unit at Georgetown, they had a place where I could lie down and sleep if I needed to. They were just so good about all of that.”
She believes trial participation among people with no symptoms or very early symptoms will continue to rise now that testing options expand, more support resources are becoming available, and early HD has become more of a focus than ever before.
“From the feedback I get, more people who are in that prodromal or presymptomatic stage feel ready to participate and will try just about anything if it will potentially delay onset or help with a cure,” she said.
