USD History

04/23/2026

From Kenneth P. Serbin, professor of history: As the reportedly dysfunctional FDA faces demands for greater clarity in the wake of rare-disease drug denials, uniQure continues to seek a path to get AMT-130, its historically efficacious Huntington’s disease gene therapy, approved. After reneging on its promise to allow uniQure to apply for AMT-130 approval in 2026, the FDA recommended a new, Phase III clinical trial. Sen. Ron Johnson, a Republican, has launched an investigation of the FDA, and a rare disease coalition has urged President Trump to restore regulatory clarity at the agency. A possible avenue to AMT-130 approval opened on April 14. Dr. Teresa Buracchio of the FDA said at the National Organization for Rare Disorders (NORD) symposium that the agency’s “plausible mechanism framework” for approval of bespoke gene therapies might be applied “to approve other therapies.” A bespoke therapy is given to a single individual, such as “Baby KJ,” the world’s first individual to be treated, and successfully, with a personalized (customized) CRISPR gene editing therapy. Dr. Buracchio stated that the FDA is open to applying the framework “conceptually” to Huntington’s disease broadly. A therapy needs to show “substantial evidence of effectiveness and a substantial improvement that’s clear and distinct from the natural history of the disease,” she said, noting that KJ demonstrated marked improvement in symptoms and reached developmental milestones. By comparison, a slowly progressive neurodegenerative disease like HD “is going to be a harder case to make,” Dr. Buracchio said. At the NORD symposium, uniQure’s Dr. David Margolin addressed the FDA’s concerns. Dr. Margolin stated that HD’s slow progression makes it nearly impossible to show clear efficacy over a short period. AMT-130 demonstrated a 75 percent slowing of HD progression over three years. Regarding the use of Enroll-HD patient registry data in place of a placebo in uniQure’s analyses, Dr. Margolin pointed out that the difference between AMT-130 clinical trial participants and the individuals uniQure selected from Enroll-HD was negligible. “I know there’s active dialogue with FDA and the Huntington’s disease organizations regarding how to interpret and best utilize these clinical scored measures, and that’s an ongoing process,” Dr. Margolin stated. In the current political and business climate, perhaps the HD community also needs a celebrity connection, as biotech observers have noted with dark humor. “I guess people living and dying with Huntington’s disease need an influencer/podcaster to text Trump,” said STAT senior biotech writer Adam Feuerstein, who shared an item about podcaster Joe Rogan receiving a promise from Trump of immediate FDA approval for a psychedelic treatment. “That’s how the FDA works these days.” Read more in my latest article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

04/08/2026

From Kenneth P. Serbin, professor of history: Two key political developments could aid uniQure’s effort to seek approval of its historically efficacious Huntington’s disease gene therapy, AMT-130, from the FDA: a senatorial probe of the FDA and a letter to President Trump from rare-disease advocates. uniQure is preparing for yet another meeting with the FDA to discuss the potential Phase III large-scale clinical trial required by the agency to further test the efficacy of AMT-130. In September 2025, uniQure revealed that 17 of the individuals receiving the highest dose of AMT-130 in its Phase I/II trial had a slowing of progression of HD by 75 percent. The FDA, seen by many biotech observers to have become dysfunctional under the Trump administration, then surprisingly reneged on a promise to allow uniQure to apply for approval in 2026. On March 9, Wisconsin Senator Ron Johnson, a Republican, announced that he had launched an investigation of the FDA because it had rejected drug applications for several rare diseases. Johnson described the FDA’s request for a new AMT-130 trial, which would include a deeply invasive sham surgery for participants not getting the actual drug, as “bureaucratic idiocy.” The senator added: “We’re going to find out exactly what issues the FDA listed for their ‘nos’.” On April 1 the Rare Disease Advocacy, Biotechnology, and Investor Coalition sent a letter to President Trump and other administration leaders. The letter urged them to restore regulatory clarity at the FDA as it considers a new leader for the agency’s Center for Biologics Evaluation and Research, which evaluates gene therapies such as AMT-130. Its controversial director, Vinay Prasad, M.D., has resigned for the second time after criticism from biopharma executives, investors, and members of Congress. The coalition includes nearly 100 patient disease advocacy groups, biotech executives, and investors. The letter noted that the Center had become less flexible in overseeing rare disease clinical trials. “We believe it is of the utmost importance that the FDA chooses [for the Center] a leader who understands the unique challenges of rare disease development and respects and values the views of patients and physicians,” their letter stated. Read more in my latest article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

03/05/2026

From Kenneth P. Serbin, professor of history: Delaying but not blocking AMT-130, uniQure’s emerging gene therapy to slow Huntington’s disease progression, the FDA “strongly recommended” that the company conduct a full-blown, Phase III clinical trial, rather than assess an application for drug approval based on an earlier trial that showed historic efficacy. The news came in a March 2 uniQure press release, relying on official minutes from the company’s January 30 high-priority meeting with the FDA about the AMT-130 program. The drug has been shown to slow the progression of by HD symptoms by as much as 75 percent. This action reflects the more conservative trend of at least parts of the FDA under the Trump administration. “While we did not reach alignment on a submission pathway based on the Phase I/II data, we believe the totality and durability of our data warrant continued substantive dialogue” with the FDA regarding “regulatory flexibility,” uniQure CEO Matt Kapusta stated. “We remain committed to engaging with the FDA to determine a clear, scientifically grounded, and efficient path forward for AMT-130. We are deeply grateful for the resilience and support of the Huntington’s disease community and remain committed to standing with patients and their families.” On February 24, a top uniQure scientist presented an updated analysis of AMT-130 at the 21st Annual HD Therapeutics Conference, sponsored by CHDI Foundation. Like other potential remedies, AMT-130 lowers (reduces) the amount of defective huntingtin protein. “We have multiple shots on goal in the huntington-lowering arena, things like uniQure,” CHDI CSO Dr. Robert Pacifici said. “While it's true that none of them have made it out the other end with a positive ruling in a pivotal Phase III trial, we're at the precipice of the types of signals that will indicate that there is a clinically meaningful benefit by lowering huntingtin.” Dr. Cristina Sampaio, CHDI’s chief medical officer, observed that companies other than uniQure have faced changes in course with the FDA. The changes in the approval process are “problematic,” she said. Some scientists think AMT-130 needs more work. Read more in my latest article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

02/17/2026

From Kenneth P. Serbin, professor of history: With 15 million people estimated to lose their medical coverage because of Trump administration policies, America has once again entered a health crossroads. As a Huntington’s disease gene carrier who for many years hid that fact from the very system that was supposed to help me – “an absolutely absurd situation”– I rejoiced when Obamacare guaranteed coverage for those of us with pre-existing conditions. Like many Americans, my family and I have struggled with many other aspects of this supposed “system.” As an HD advocate, I embrace health care as a human right. We need so much more than Obamacare. I support Senator Bernie Sanders’ Medicare for All Act of 2025. Medicare for All would involve a national health insurance system. It would cover items and services to diagnose, treat, or rehabilitate a health condition, including hospitalization and prescription drugs, mental health, dental and vision services, long-term care, and reproductive care. There would be no co-pays. All U.S. residents would be included from birth. Sanders’ criticisms of the current system ring true with people’s frustrations. In his words, America’s great political challenge is to decide whether to continue to focus on profits, or do we create a system where “every man, woman, and child in this country should, in a cost-effective way, be guaranteed quality and equitable health care regardless of their economic status.” Sanders has a detailed plan to generate trillions of dollars to support Medicare for All. Sanders notes “overwhelming support” for Medicare for All in polls. The bill now has 111 co-sponsors in the House of Representatives and 17 in the Senate. “Scientists will be freed to concentrate on developing breakthrough drugs, rather than tailoring their research so that pharmaceutical firms can maintain record profits,” Sanders adds. In the HD community and beyond, let us join hands to advocate for Medicare for All. Read more in my latest article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

01/30/2026

From Kenneth P. Serbin, professor of history: On January 22 Huntington’s disease organizations delivered two petitions to the FDA, demanding that the agency reverse its rollback on uniQure’s application for its HD gene therapy. In September, uniQure announced that its drug, AMT-130, had slowed the progression of HD by 75 percent over three years – a historic first. However, reflecting what critics saw as growing dysfunction under the Trump administration, the FDA abruptly switched gears regarding its agreed-to plan for considering AMT-130. HD advocates quickly organized two online petitions, garnering 48,000-plus signatures. “We can’t delay any longer,” Lauren Holder, a Help4HD International advocate and (like me) an HD gene carrier desperate for a therapy like AMT-130, said in a Facebook video at the FDA. “It’s important that they hear us.” Holder said that she often hears from HD-affected individuals that “‘I don’t want to be dying from HD; I want to be living with HD.’ These gene therapies and gene-modifying drugs are what get us to that point.” In a final, intense push for signatures, Holder on her January 16 podcast interviewed petition organizer Jeremy Renz (pictured here), whose wife tested positive for HD. “There’s more young people that are testing,” Renz told Holder. “There’s more young people who are at risk that are getting ramped up and ready to fight the fight.” Crucially, the high priority meeting that uniQure will soon hold with the FDA will include a representative of the community. Holder and Renz saluted how the HD community had united to work hard on AMT-130 advocacy. Read more in my latest article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

11/19/2025

From Kenneth P. Serbin, professor of history: As uniQure seeks to overcome a decision by the FDA to roll back its consultations regarding the firm’s promising gene therapy for Huntington’s disease, the community has begun to rally by organizing two petitions asking the agency to support the remedy. uniQure and others in the biotech sector believe that the FDA has become dysfunctional under the Trump administration. On November 13, STAT reported on a private dinner held by uniQure CEO Matt Kapusta with investors on November 11. According to the report, uniQure hopes to find a way forward for AMT-130. “We remain fully committed to people living with HD, who have no disease-modifying treatment options,” Tom Malone, uniQure’s senior director of communications, e-mailed me. “We are wholly focused on working with the FDA to determine the best path forward to rapidly bring AMT-130 to patients and their families in the U.S.” The STAT report noted that Kapusta “doesn’t like all the drama” inside the FDA surrounding its upending of uniQure’s plans. Aiming to stabilize the agency, the FDA has named Richard Pazdur, M.D., a 26-year veteran of the entity, to run its center for regulating and approving new drugs. Dr. Pazdur’s appointment is a sign the Trump administration is seriously addressing the “FDA dysfunction,” Kapusta said at the investor dinner. According to STAT, Kapusta’s remarks at the dinner “reflected biotech’s frustration with volatility” at the FDA. uniQure was disturbed by the fact that the FDA’s new message on AMT-130 was “delivered by lower-level staffers” and not senior decision-makers, STAT reported. The firm “feels like it was screwed over by the FDA, and rightfully so,” one investor told STAT. As of November 15, the two online petitions to the FDA from HD advocates have already garnered almost 9,000 signatures. These moving, persuasive petitions effectively portray the devastating impact of HD on patients and families and the historic breakthrough towards a treatment achieved with AMT-130. They effectively demonstrate the profound need for the drug and urgent action by the FDA. I immediately signed one. I urge everyone to do so. Read more in my latest article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

11/08/2025

From Kenneth P. Serbin, professor of history, Less than six weeks after uniQure announced that its gene therapy drug slowed the progression of Huntington’s disease by 75 percent, the FDA has backtracked on its conversations with the company regarding the timeline and data needed for potential approval of the remedy. The company’s plan to apply for approval of the drug, AMT-130, in early 2026 and launch it into the market later that year may no longer be possible. In a November 3 press release uniQure announced that, after a recent meeting with the FDA, the company believes that the “FDA currently no longer agrees” that data from its clinical trial of AMT-130 using an “external control” as a comparison “may be adequate to provide the primary evidence in support of” an application for approval. The external control refers to data taken from Enroll-HD, the global HD patient registry, as a baseline, rather than those taking a placebo, to compare with those on AMT-130. uniQure had gotten FDA permission to use Enroll-HD. “This is a key shift from prior communications with the FDA in multiple … meetings over the past year,” the uniQure release stated. “Consequently, the timing of the BLA [Biologics License Application] submission for AMT-130 is now unclear.” “We are surprised by the FDA’s feedback at the recent pre-BLA meeting, which is a drastic change from the guidance the FDA provided in November 2024,” said uniQure CEO Matt Kapusta. “This news is unexpected, and we are truly disappointed for people living with HD.” At the top of its website’s homepage the FDA has the phrase “first six months of FDA reforms,” including “unleashing cell and gene therapies.” Science and medicine do not act in a vacuum and are impacted by politics and society, as HD family member and historian Alice Wexler has brilliantly illustrated in her writings. The New York Times has reported on the “collapse of the FDA” under Robert F. Kennedy Jr. STAT reported that since uniQure and the FDA had set drug submission “benchmarks” last year, “the agency has undergone considerable changes. Vinay Prasad, a physician with a reputation for taking a more conservative view of gene therapies, now oversees the division with authority over AMT-130.” STAT also reported on the “slow-boiling feud” at the division, which has lost hundreds of employees. Dr. Prasad pushed out “top cell and gene therapy regulators.” On November 5 HDSA and four other HD entities issued a joint statement: following the regulatory update about uniQure, “it’s clear that stronger alignment and collaboration among HD patient and family organizations are more critical now than ever.” Read more in latest article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

10/21/2025

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10/17/2025

From Kenneth P. Serbin, professor of history: After 17 years of estrangement because of disagreements over family caregiving, in July I visited my hometown in Lake County, Ohio, to reconnect with my younger sister Donna. She began having Huntington’s disease symptoms in 2020. In early 2023, Donna told me, via Facebook, that she had tested positive for HD but did not mention whether she had symptoms. I did not respond at that time because of unforeseen circumstances. In March of this year, I finally responded to my sister, my only sibling. We then spoke on the phone. Donna explained that she had HD symptoms. She also revealed that one of her three sons, 37-year-old Greg, had also tested positive for the HD gene. At the end of this emotional phone call, we expressed our love for each other and our respective families. I felt an enormous relief at having reconnected with my sister. As an advocate, brother, and gene carrier who has luckily hit 65 without apparent symptoms, I felt duty-bound to check up on my younger sister. She is 63. Our mother Carol died of HD at age 68 in 2006. On July 15 Donna, her husband Barry, my nephew Greg, my wife Regina, and I had a three-hour dinner. Though it was, potentially, a very awkward reunion, we reconnected in a most cordial manner. We were family, and we knew we had to reunite to offer mutual support and understanding in the fight against HD. We discussed potential HD disease-modifying treatments, including uniQure’s AMT-130. On September 24, when uniQure announced that AMT-130 had successfully slowed the progression of HD, I texted Donna and Greg with the news. “Wonderful news!” they both responded. Although it is unclear whether Donna, Greg, and I will even have access to AMT-130, the news of its efficacy still brings us immense hope. “It’s day one of a new world, but it’s up to us to define the characteristics of that world and make sure that it’s capable of delivering the benefit to everyone who needs it,” said Dr. Ed Wild, an investigator on the uniQure program and senior advisor to the company. Read more about AMT-130, including the important details that must be resolved and a critique of the drug, in my latest blog article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

09/25/2025

From Kenneth P. Serbin, Ph.D., Department of History: AMT-130, a gene therapy developed by uniQure, has successfully slowed the progression of Huntington’s disease. Though not a cure, it is the first evidence that scientific progress translates into meaningful results for those suffering from HD. As a gene therapy, AMT-130 requires just one application. According to data reported by uniQure on September 24, AMT-130 demonstrated a 75 percent slowing in the progression of the disease over a three-year period. “High-dose AMT-130 also demonstrated statistically significant slowing of disease progression as measured by TFC, a key secondary endpoint, and favorable trends across additional clinical measures,” the uniQure press release stated. TFC is total functional capacity. The company reported that AMT-130 also reduced the measure of a protein known as neurofilament light, a marker of disease that reveals stress on the brain. The clinical trial showed “favorable trends” in other secondary measures of movement and cognitive function. Clinical trial results demonstrated that AMT-130 is safe and well-tolerated. “I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington’s disease, where an urgent need persists,” Dr. Sarah Tabrizi, a leading HD specialist, stated in the release. “These data indicate that AMT-130 has the potential to meaningfully slow disease progression – offering long-awaited hope to individuals and families impacted by this devastating disease.” In early 2026, uniQure plans to apply to the FDA for drug approval. If approved, the drug would be launched in the U.S. later in 2026. On the whole, despite the complexities involved in getting the drug widely administered, this is wonderful news for the HD community. Read more in my latest blog article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.

07/28/2025

From Kenneth P. Serbin, Professor of History: In 2022 Dorlue Schulte of San Diego died at home after a long struggle with Huntington’s disease. To benefit research, Dorlue donated her brain to the Harvard Brain Tissue Resource Center (HBTRC). “They can get hundreds of samples from one donation, so it’s truly the gift that keeps on giving,” said Dorlue’s husband and main caregiver Doug. Doug observed that HD researchers are “coming up with great ways to inspect the brain to learn from them.”
“Scientists now have the ability to look at every cell in the brain and look at the mRNA and the proteins in the cells to see if they are resistant or not resistant to Huntington’s disease and, more importantly, probably, the timing of when (cell) death occurs,” Doug explained. “They’ve got to compare it with a brain that’s not diseased.” Besides research on HD mice and many other non-human species, study of HD brains provides “precious” human data in the quest for treatments, in the words CHDI CSO Dr. Robert Pacifici. The sole funder of the HBTRC is the NIH, HBTRC director and HD researcher Dr. Sabina Berretta said. Harvard has sued the federal government to try to block the Trump administration’s freezing of billions in research funds. The government also seeks to eliminate $783 million in NIH funding. Dr. Berretta explained that the HBTRC NIH contract “will end in October 2025. It is not known at this time whether and how the new contract, expected to start in November 2025, will be impacted.” She added that “the current funding uncertainty creates some challenges, particularly for talent retention and long-term planning, both critical to our work.” Doug explained how he and Dorlue came to a decision about donating her brain and the details of the process. The opportunity to donate is “a blessing,” he said. The HBTRC does crucial work in the quest for a cure. Read more in my latest blog article.

HD is a genetically caused brain disorder that causes uncontrollable bodily movements and robs people's ability to walk, talk, eat, and think. The final result is a slow, ugly death. Children of parents with HD have a 50-50 chance of inheriting the disease. There is no cure or treatment.