Hope on hold: FDA decision detrimentally impacts HD families
The genetic mutation that causes Huntington’s disease (HD) was discovered in 1993, and yet HD families, including my own, are still waiting for something – anything – to slow disease progression and extend the amount of quality time we have with our loved ones. We are eager to hold onto hope that a disease-modifying treatment could be available soon, but that has been difficult in recent months due to a decision by the US Food and Drug Administration (FDA) to shift the goalposts on a promising gene therapy.
Huntington’s is a rare neurodegenerative disease that affects 41,000 Americans, with another 200,000 being at-risk. It is characterized by physical and cognitive decline paired with a laundry list of potential psychiatric symptoms; it gradually takes away the ability to walk, talk, and participate in daily life. Symptoms typically appear in middle age but can appear in childhood or old age. Every child of a parent with HD has a 50-50 chance of inheriting the disease.
My own family was surprised to learn my brother had HD in 2014 because we didn’t know we were an HD family; my dad and grandpa both had HD but never received the correct diagnosis. We had hoped that finding answers for my brother would help him get better. Instead, his diagnosis meant that 10 family members, including me and my kids, might have inherited HD. We were all overwhelmed by what we were up against as we adjusted to this new life.
My brother has changed a lot in the last ten years. He now relies on others for all aspects of care, and communication is challenging. I tested negative in 2019, but I continue to worry about my family. I also care deeply for those I have come to know in the HD community. I’ve attended many community events, volunteered at a youth camp, and worked with a small group of community advocates. I’ve also interviewed dozens of people to write a book about HD. What I have found is a community that welcomes anyone impacted by HD as family – a chosen family that works tirelessly to support and advocate for each other.
Research holds promise for my friends and family to have a brighter future. On September 24th, 2025, uniQure announced unprecedented results of a combined Phase I/II clinical trial for their investigational medicine, AMT-130, a one-time gene therapy. At the three-year mark, patients in the high-dose cohort showed a 75% slower decline in motor and cognitive function, and the therapy had a strong safety profile. This is the first-ever treatment to show HD progression can be slowed. There was immediate buzz within the HD community as we dared to hope for a better future.
Unfortunately, our hope was short-lived.
Just weeks later, the FDA indicated it no longer agrees that natural history data can be used as a comparator arm in uniQure’s application for accelerated approval. Using a natural history dataset is an accepted method to measure disease progression in rare diseases without subjecting patients to risky procedures. In this case, it is the most ethical choice, given that delivery of this gene therapy involves an approximately 10-hour brain surgery. Using a placebo arm instead would require patients to undergo a sham procedure (i.e., undergoing anesthesia without receiving treatment). This is invasive, and patients are likely to experience too much neurodegeneration to qualify for treatment by the time they become eligible.
The FDA’s announcement came as a surprise because uniQure and the FDA consulted with each other throughout the clinical trial process and agreed on conditions for moving AMT-130 through that process. The FDA even awarded AMT-130 Breakthrough Therapy and other designations. Despite indicating they were on board throughout, the FDA has now changed course. Accelerated approval is on hold, and next steps are uncertain.
The HD community knows to be cautious about placing too much hope in research, because we’ve been here before. Other promising clinical trials have been halted or paused due to safety issues or unmet endpoints. This time, however, the issue isn’t safety or efficacy; the issue is the FDA backtracking on its commitment to allow natural history data as a control. Their reversal is astonishing and has serious consequences for tens of thousands of families like mine.
HD progresses slowly, so it would be easy to think that the HD community has time. However, HD’s long disease progression means our families endure loss after loss, generation after generation. Once neurodegeneration begins, long before symptoms appear, it is very difficult to halt or slow it down. We don’t have time to wait years for uniQure to gather more data for a placebo arm. Each year of delay means more of our family members will experience too much neurodegeneration to be eligible for treatment, setting them up for decades of decline. Our loved ones deserve better; they deserve the chance to look forward to a longer and healthier future – a future that seemed within reach when uniQure first announced its AMT-130 clinical trial results.
The FDA’s actions have introduced unpredictability into the drug approval process, which has consequences beyond HD. The potential to treat rare diseases is at stake as other rare disease communities face similar challenges. Please join me and more than 38,000 others who have signed at least one of two petitions calling on the FDA to uphold its previous commitment to an accelerated pathway for AMT-130. In addition, please contact your members of Congress to urge them to support a fair review of AMT-130.
It’s not too late to protect the future we dared to believe was finally possible.
Article was originally posted on LinkedIn on January 6, 2026.