For Huntington’s Disease Awareness Month, reflections on teaching about this devastating disorder at the University of San Diego

  

First proclaimed by President George H. W. Bush in 1991, Huntington’s Disease Awareness Month (May) encourages affected families to share their stories about this rare neurological disorder with the wider world.

 

For that reason, among others, I served on the board of the San Diego Chapter of the Huntington’s Disease Society of America (HDSA) from 1998-2010. In this blog, begun in 2005, I have written articles commemorating HD Awareness Month.

 

A 2019 posting about HD Awareness Month featured a photo of me pointing to HDSA #LetsTalkAboutHD flyers posted on my office door at the University of San Diego (USD), where I teach history and research science and technology studies.

 

As a fulfillment of a long-term goal to advance both awareness-building and deepen my knowledge of HD science, in the spring semester of 2025 I inaugurated a new course, A History of the Brain: Examining Huntington’s Disease. Professors often say that the best way to learn a subject is to teach it. Student feedback is crucial in this process.

 

This month, in the third offering of the course, I distributed a flyer containing HD Awareness Month promotional material from HDSA and the Huntington’s Disease Foundation.

 

Each holding a flyer, three students – Ana-Lucia Moreno, Ava Puorro, and Mia Wilde – had a picture of me taken with them in the classroom and posted it on Wilde’s Instagram with the title “National Huntington’s Disease Awareness Month.”

 

“Best class ever with Dr. Serbin, who has Huntington’s disease and taught us so much about it in class!” they wrote on the posting.

 

They included the link to this blog. “Watch his blog to learn more about HD and how we can make all people feel included.”

 

 

From left to right, Mia Wilde, Gene Veritas (aka Kenneth P. Serbin), Ana-Lucia Moreno, and Ava Puorro in Wilde’s Instagram post about HD Awareness Month. The jacket I am wearing is much-appreciated swag from the Annual HD Therapeutics Conference, sponsored by CHDI Foundation, Inc., the biggest private funder of HD research (personal photo).

 

Keys to understanding the history of HD

 

A History of the Brain has great relevance to the present. At the outset, I acknowledge that I am not a neuroscientist but a historian, HD gene carrier, and advocate.

 

An introductory course that fulfills the history requirement in USD’s core curriculum, A History of the Brain teaches basic skills in how to interpret history. The students have a wide variety of majors and career interests, including premed, neuroscience, biotech, business, natural sciences, engineering, and the humanities. The course also counts towards a major or minor in history.

 

I lecture on the basic scientific understanding of the brain from antiquity to the present, based on the masterful book by Andrew P. Wickens, A History of the Brain: From Stone Age surgery to modern neuroscience. It helps provide an overview of humanity’s understanding of the brain in understandable terms.

 

To launch discussion about the disease, students do short writing assignments based on the course readings. They include neurologist Thomas Bird’s Can You Help Me? Inside the Turbulent World of Huntington Disease. As I stated in my review of the book, “With non-technical, limpid prose, Dr. Bird tells the full story of HD’s wide-ranging medical, socioeconomic, and legal implications through a series of poignant vignettes, based on hundreds of HD cases."

 

The students also read two classic works by prominent HD family member and historian Alice Wexler, Ph.D. In The Woman Who Walked into the Sea: Huntington’s and the Making of a Genetic Disease, Dr. Wexler explains the deep stigma and misunderstanding about HD that developed in the nineteenth and twentieth centuries. In Mapping Fate: A Memoir of Family Risk and Genetic Research she chronicles the crucial work by her family and a myriad of scientists to discover the huntingtin gene in 1993.

 

Emotional debates and discussions

 

Many days in the course produce deeply emotional debates and discussions.

 

My students’ recognition of the need for social inclusion for all echoes the course’s deep exploration of the stigma and discrimination associated with HD, other neurological disorders, mental illness, and disabilities.

 

Those themes emerge in the books about HD and in the selection of articles from my blog included in the course readings. For its contributions in giving a voice to the HD community, last year my blog received the 11th Victor Gonzalez Santos Community Award, which supports local families in San Diego with HD. My articles, which include stories of my family’s struggles with HD, and my discussions with the students add a deeply personal element to HD and the cause to defeat it.

 

The course studies in details HD’s triad of devastating symptoms: involuntary movements, cognitive loss, and behavioral and psychiatric difficulties. We also delve into many other difficult challenges faced by the HD community, such as genetic testing, family planning, and bioethical issues like abortion and suicide. We also discuss the quest for treatments of this still incurable disorder.

 

Students see how I bared my heart in blog articles like the one about my mother’s final moments before dying from HD and the revelation that I carried the HD gene. As a result, I need to be prepared to talk in class about the most devastating aspects of the disease and the fears of experiencing them myself.

 

College classes provide an exercise in intellectual freedom and debate, with a professor being open to all views. In one class last year we intensely debated police misunderstanding and mishandling of HD-affected individuals, who are often seen as being under the influence of drugs or alcohol.

 

I introduced the students to something new for most of them: the Psychiatric Emergency Response Team, which has specialists trained to interact with and identify resources for those with behavioral health issues and who may pose a threat to themselves or others. The students concluded that this team was the appropriate alternative to calling the police in the case of HD or other disorder.

 

Invaluable insights

 

The course closes with an important religious perspective on the HD cause. We ponder the question, “how could God allow people to suffer from disease?” We examine Pope Francis’s historic audience with the HD community in 2017 and his declaration that HD should be “hidden no more!”

 

One of my projects at USD is to publish an annotated collection of about a dozen or some of my blog articles.

 

My interaction with the students and their thoughts on my blog and the HD cause will provide invaluable insights for that project.

 

A ‘very meaningful’ experience

 

The course has also underscored for me the fact that Huntington’s disease is still not a household word in the U.S. as compared to Alzheimer’s, Parkinson’s, ALS (amyotrophic lateral sclerosis), and other disorders. For most of the students, it is their first exposure to HD.

 

HD families still lack an effective therapy.

 

In a very poignant way, the course introduces young people to something we all share: mortality. Tragically, last year a vibrant and accomplished 42-year-old USD sociology professor, Greg Prieto, Ph.D., died of cancer – after offering his own reflections on facing death.

 

With A History of the Brain, I hope to have move us a bit further towards the greater awareness that the HD community still needs.

 

My students’ HD Awareness Month Instagram post is an example of the impact the course has had.

 

In an e-mail to me, Mia Wilde reported that the post had some 600 views and 100 likes, “a really great amount of engagement.”

 

“Another person reached out asking what Huntington’s disease was, so I gave them a brief overview about it being a hereditary disease and shared some of what we learned in class,” Wilde wrote.

 

Another person told Wilde that “it was such a thoughtful thing that we were doing because they had a friend who had Huntington’s disease before, which I thought was very meaningful to hear.”

As FDA faces demands for greater clarity, uniQure presses ahead in search for Huntington’s disease gene therapy approval

  

As the reportedly dysfunctional U.S. Food and Drug Administration (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.

 

On March 2, after having surprisingly reneged last year on its promise to allow uniQure to apply for AMT-130 approval in 2026, the FDA “strongly recommended” that the firm conduct a new, full Phase III clinical trial.

 

In March, Wisconsin Sen. Ron Johnson, a Republican, launched an investigation of the FDA’s rejections of rare disease drugs. He 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.”

 

In an April 1 letter, the Rare Disease Advocacy, Biotechnology, and Investor Coalition urged President Trump and top administration health officials to restore regulatory clarity at the FDA.

 

A new way to win approval?

 

A possible avenue to AMT-130 approval opened on April 14. Teresa Buracchio, M.D., head of the FDA’s Office of Neuroscience, said at the National Organization for Rare Disorders (NORD) symposium in Arlington, VA, that the agency’s “plausible mechanism framework” for approval of bespoke gene therapies might be applied “to approve other therapies.” The news site Fierce Biotech reported on the symposium.

 

A bespoke therapy is given to a single individual, such as “Baby KJ,” the world’s first individual to be treated with a personalized (customized) CRISPR gene editing therapy, in 2025. KJ was born with a rare metabolic disease, severe carbamoyl phosphate synthetase 1 (CPS1) deficiency. The child is now thriving.

 

After FDA leaders raised the topic of individualized therapies in a November 2025 The New England Journal of Medicine article, the FDA in February issued a draft guidance for a new path to such treatments, calling it the “plausible mechanism framework.”

 

Dr. Buracchio observed that the framework is not specifically an approval pathway but a set of regulatory principles being applied to customized therapies for the first time, Fierce Biotech reported.

 

The special challenges of HD science

 

The Fierce Biotech article noted that Dr. Buracchio’s comments “offered some clarity to a confused rare disease sector rattled by high-profile regulatory drama.” That drama has resulted in part from uniQure’s use of patient registry data (also known as a natural history study) to analyze AMT-130, which was rejected by the FDA “even as such methods are part of the criteria that could enable approvals for tailored gene-editing therapies under the plausible mechanism framework.”

 

In March, the FDA had pointed out that AMT-130 is not an individualized therapy.

 

However, Dr. Buracchio said that the plausible mechanism framework “shouldn’t be a disadvantage” to non-individualized therapies.

 

Dr. Buracchio stated that the FDA is open to applying the plausible mechanism framework “conceptually” to Huntington’s disease broadly, or other diseases of comparably-sized populations.

 

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. “That’s because slowing the rate of decline is much harder. So, to me, this is less of a number issue and more of a nature of the disease issue.”

 

Presenting AMT-130 to the rare disease symposium

 

At the NORD symposium, David Margolin, M.D., Ph.D., uniQure’s vice president for clinical development, gave a presentation on AMT-130, addressing the FDA’s concerns.

 

As reported by Fierce Biotech, in response to the FDA’s requirement that the company run a Phase III trial and Dr. Buracchio’s point about the slowness of HD, Dr. Margolin stated that this slow progression makes it nearly impossible to show clear efficacy over a short period. This creates an “ethical challenge” when giving some patients a placebo or having them undergo the sham surgery.

 

As presented by Dr. Margolin at numerous conferences, including the key 21st Annual HD Therapeutics Conference in February, AMT-130 demonstrated a 75 percent slowing of HD progression over three years. (The conference is sponsored by CHDI Foundation, Inc., the largest private funder of HD research.) This was the first time that a drug has delayed HD.

 

Dr. David Margolin at the 2026 HD Therapeutics Conference (photo by Gene Veritas, aka Kenneth P. Serbin)

 

Enroll-HD in place of a placebo

 

A second Fierce Biotech article on the NORD symposium focused on how academics and biopharma leaders are breaking the mold of traditional clinical trials with creative methodologies, aiming to garner interest and support from peers and regulators.

 

A common approach in rare disease drug development is the use of an external control or comparator, which replaces the placebo in a classic clinical trial. As noted, instead of a sham trial, uniQure took this approach by using data from the HD patient registry, called Enroll-HD.

 

With more than 22,000 participants, Enroll-HD is “one of the most remarkable prospective registry trials that's ever been run,” according to CHDI Chief Scientific Officer Robert Pacifici, Ph.D.

 

Tracy Beth Høeg, M.D., Ph.D., the acting director of the FDA’s Center for Drug Evaluation and Research, stated at the NORD event that the agency is finalizing guidance on external controls. This, she added, will hopefully “give clarity to sponsors about what sort of evidence we would be looking for and willing to accept for approval of rare disease drugs.”

 

As reported by Fierce Biotech, Dr. Margolin spent much of his NORD talk on uniQure’s use of a statistical technique known as “propensity score matching.” As he explained at the Therapeutics Conference, this involves finding in Enroll-HD individuals similar to those in the uniQure trial and including them as controls. At the NORD meeting, he pointed out that the difference between AMT-130 clinical trial participants and the individuals uniQure selected from Enroll-HD was negligible.

 

Dr. Margolin also responded to the FDA’s criticism that one of the clinical trial measurements uniQure used for AMT-130 was too subjective, leaving the participants susceptible to a placebo effect that could not be detected when using Enroll-HD.

 

An ongoing dialogue with the FDA

 

“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.

 

Meanwhile, the HD community and its allies continue to pressure Congress and public officials to focus on HD and bring AMT-130 a fair hearing at the FDA.

 

Or, in the current political and business climate, perhaps the HD community also needs a vast stroke of good luck, celebrity connections, and publicity, as biotech observers have noted with dark humor.

 

Joe Rogan to the rescue?

 

On April 18, Pearl Freier, president of Cambridge Biopartners, Inc., asked on the social media platform X how the HD community could overcome an FDA rejection based on the “personal negative opinion” of FDA Commissioner Marty Makary and/or U.S. Secretary of Health and Human Services Secretary Robert F. Kennedy Jr.

 

She added: can the HD community make a deal with growth stage venture capital firm and prediction market company “Kalshi and/or Polymarket?”

 

Adam Feuerstein, the senior writer covering biotech at the essential STAT, responded to Freier’s post: “I guess people living and dying with Huntington’s disease need an influencer/podcaster to text Trump. That’s how the FDA works these days.”

 

Feuerstein linked to an X post detailing how popular podcaster Joe Rogan revealed how the president “IMMEDIATELY offered FDA approval for a psychedelic treatment in a text chain Because the data was SO CONVINCING and STUNNING.” The treatment is for depression and other conditions.

 

Finding comfort in Pope Francis’ embrace of the HD community

 

These are trying times for the world, with the U.S. again in a major war and world peace once again at risk. For the HD community, it is distressing that AMT-130 is rejected after seven years of clinical study by uniQure.

 

For comfort I remember highlights of the HD cause such as Pope Francis’ 2017 audience with HD families, declaring that the disease should be “hidden no more” and HD families respected and loved. I also look with hope to the first American head of the Church, Pope Leo XIV, who has continued Francis’ emphasis on mercy.

A Senate probe of the FDA and a letter from advocates to Trump could aid in approval of Huntington’s disease gene therapy

  

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 U.S. Food and Drug Administration (FDA): a senatorial probe of the FDA and a letter to President Trump from rare-disease advocates.

 

As reported widely, 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. Since its start in 2019, the Phase I/II trial has involved some 45 people. In September 2025, uniQure revealed that 17 of the individuals receiving the highest dose of AMT-130 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 Sen. Ron Johnson, a Republican, announced that he had launched an investigation of the FDA because it had rejected drug applications for several rare diseases.

 

Senator Ron Johnson (official congressional photo)

 

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.”

 

AMT-130 requires a twelve-hour surgery to inject the drug deep into the brain. The sham surgery would serve as a placebo in the clinical trial.

 

“You’re expecting people to go through sham surgeries where they get holes drilled in their heads?” Johnson said. “That’s just unbelievable.”

 

As part of his probe, Johnson is seeking denial letters from the FDA. Referring to the agency, he said that the “stories are outrageous. It just appears that they’re looking for excuses to say no.”

 

The senator added: “We’re going to find out exactly what issues the FDA listed for their ‘nos’.”

 

A sham surgery could pose ‘significant risk’

 

Johnson’s office did not respond to my request for an interview.

 

Walid Abi-Saab, M.D., uniQure’s chief medical officer, told the key publication Neurology Today that a sham controlled study “could impose significant risks and burden to patients” and that some people may consider it unethical.

 

Dr. Abi-Saab added that volunteers facing the sham surgery could not access other potentially disease-modifying therapies advancing through trials involving several years of observation.

 

Early in the AMT-130 program, uniQure used a sham surgery in several individuals but then stopped precisely because of ethical concerns.

 

Advocacy groups such as the Huntington’s Disease Youth Organization (HDYO) also have cautioned against the sham surgery.

 

In a March 6 e-mail, the organization stated that the “use of a sham neurosurgical procedure – requiring participants to undergo the risks of major surgery to the head including a lengthy time period under anesthesia without the possibility of therapeutic benefit – places an unnecessary burden on individuals already facing a progressive and fatal condition.” HDYO urged the use of “alternative trial designs … while minimizing avoidable risk to participants.”

 

Seeking to restore regulatory clarity

 

According to a report by Reuters, on April 1 the Rare Disease Advocacy, Biotechnology, and Investor Coalition sent a letter to President Trump, U.S. Health Secretary Robert F. Kennedy Jr., Medicare head Mehmet Oz, M.D., and FDA Commissioner Marty Makary, M.D.

 

The letter urged the leaders to restore regulatory clarity at the FDA as it considers a new leader for the agency’s Center for Biologics Evaluation and Research.

 

Headed by Vinay Prasad, M.D., who has resigned for the second time, the Center evaluates gene therapies such as AMT-130. Dr. Prasad’s departure follows a series of controversies involving the review of vaccines, gene therapies, and biotech drugs, including reversals of FDA promises. Biopharma executives, investors, members of Congress and others have criticized his actions.

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.

 

The group has observed a drop in rare disease investment because of the uncertainties caused by the FDA.

 

“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.

 

A chance for the FDA ‘to reset’

 

An April 1 report by the news site BioPharmDive echoed the advocates’ critical analysis of the FDA.

 

The report observed that, after a “turbulent year” at the FDA caused by “constant leadership changes” and “erratic decision making,” the agency is as “unpredictable as it’s ever been.”

 

BioPharmDive concluded that Dr. Prasad’s departure by the end of April “could give the FDA a chance to reset.”  Commissioner Makary promised to name a replacement before he leaves.

 

‘We can’t afford delays for rare diseases’

 

On February 26, Florida Sen. Rick Scott, another Republican, chaired a hearing of the Senate Special Committee on Aging, which addressed the FDA’s difficulties.

 

At the hearing, physicians, biotech leaders and rare disease patient advocates criticized the FDA for stifling innovation.

 

The hearing discussed FDA reversals of previous agreements that it had made with drug makers. One advocate pointed out that, from 2024 to 2025, the FDA had 65 percent fewer advisory committee meetings for new drugs and biologics (a medicine derived from a living organism as opposed to a chemical), including for rare diseases.

 

At the hearing, New York Sen. Kirsten Gillibrand, a Democrat, pointed out that about one in ten Americans have a rare disease. She stated that the FDA is “not working how it should be” as laid out by Congress.

 

“This is heartbreaking for patients, and it’s why we can’t afford delays and disruptions in treatment,” Gillibrand observed. “Rare diseases can progress rapidly, cause irreversible harm and, in some cases, premature death.”

CHDI chief scientist: ‘at the precipice’ of treatments, Huntington’s disease community must ‘persevere’ through the stress

  

As researchers have hypothesized that lowering (reducing) the amount of abnormal huntingtin protein in the brains of people afflicted with Huntington’s disease hits at the root causes of the disease, leading companies have sought to develop drugs in response, like uniQure’s AMT-130 gene therapy.

 

The huntingtin-lowering approach has become central to the search for disease-modifying therapies that slow, halt, or reverse the course of HD, a progressive disorder still without a treatment after the discovery of the huntingtin gene in 1993.

 

"We have multiple shots on goal in the huntington-lowering arena, things like uniQure, like PTC, like Skyhawk,” Robert Pacifici, Ph.D., chief scientific officer for CHDI Foundation, told me in a video interview on February 27. “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.”

 

In our interview, Dr. Pacifici gave his customary overview of the CHDI-sponsored 21st HD Therapeutics Conference, held February 23-26 in Palm Springs.

 

Dr. Robert Pacifici (right), interviewed by Gene Veritas, aka Kenneth P. Serbin, February 27, 2026 (screenshot by Gene Veritas)

 

In my introduction, I noted that, because “it had a lot of progress,” scientifically this was the most “exciting” of the conferences that I have attended since my first in 2010.

 

However, I added, “there was stress for us in the HD community about the uniQure gene therapy program” because we were “shocked” at the abrupt backtracking of the U.S. Food and Drug Administration (FDA) on the drug despite its historic efficacy. This prompted two petitions with 48,000-plus signatures. I recalled that “so many of us in the community are still living with the burden of symptoms, including my sister, now disabled.”

 

Dr. Pacifici agreed that, until the arrival of an effective therapy, the HD community will have “some high degree of hope, but also a high degree of stress, because I think the closer we get, the more stressful it is that we're at the precipice of actually realizing this incredible journey.”

 

Dr. Pacific urged that people “continue to persevere.”

 

Watch my full interview with Dr. Pacifici in the video blow. 

 

 

A 75-percent slowing of the disease

 

At the Therapeutics Conference, a uniQure scientist presented an updated analysis of AMT-130 that “supports the validity” of its “efficacy results.”

 

With uniQure’s announcement last September that AMT-130 had demonstrated a 75 percent slowing in the progression of the disease over a three-year period, the HD community was jubilant (click here and here to read more).

 

Reports such as the BBC’s optimistically portrayed AMT-130.

 

HD and uniQure thrust into the national spotlight

 

Observers and news reports have described the Trump administration’s FDA as dysfunctional and more conservative. After the FDA surprisingly reversed field in November regarding AMT-130, the anxiety and raw tensions over the drug underscored the HD community’s yearning for an effective therapy.

 

On March 2 uniQure revealed that the FDA declined to accept its request to keep the agency’s original promise, in which the firm could apply for accelerated approval for AMT-130. Instead, the FDA “strongly recommended” that the company conduct a full-blown, Phase III clinical trial (click here to read more).

 

The controversy over AMT-130 has highlighted the FDA’s rejection of rare-disease drug programs, thrusting HD and uniQure into the national spotlight. Outlets providing coverage have included STAT, The New York Times, Bloomberg, CNN, CNBC, and the The Wall Street Journal.

 

On March 6 Vinay Prasad, M.D., the controversial head of the division within the FDA charged with evaluating gene therapies like AMT-130, resigned for the second time. While no reason was stated, the Times noted, leaders in the biotech and investor communities had long pressed the White House for his ouster.

 

Assisting the 60-plus companies involved

 

Dr. Pacifici told me that he was an “optimist” regarding the “interaction between the companies and the regulators,” who are “scientific people.”

 

“I truly believe that politics and money and all of the other perverse things that surround us, notwithstanding, that at the end of the day, the truth conquers all,” he said. “I think that they're going to look at the body of data and evidence, and eventually I think they're going to make the very best decision to get things out as quickly and as safely as possible to the patients who so desperately need these treatments.”

 

Because of the progress with huntingtin-lowering drugs like AMT-130, Dr. Pacifici noted that companies continue to allocate the “significant resources” necessary for Phase III trials.

 

The feedback from trials has enabled scientists to “hone the next generation of huntingtin-lowering therapies” and to address related questions, he added.

 

Dr. Pacifici emphasized that CHDI will continue to advise and assist uniQure and all companies seeking to develop HD therapies. More than 60 firms attended the Therapeutics Conference, which had a record attendance of 445.

 

Other key techniques

 

The conference also focused on other potential techniques in the search for therapies, such as the splicing of DNA “either to make less of a toxic protein or make more of a protein that is beneficial,” Dr. Pacifici explained.

 

Several presentations also discussed potential ways of impacting somatic expansion, the tendency of the abnormal huntingtin gene to expand over time to the point where symptoms are triggered.

 

Dr. Pacifici emphasized the need to intervene in the disease process long before symptoms arise.

 

“There's a long phase in Huntington's disease where people have the gene, but overtly, to at least the lay eye, look perfectly normal and healthy,” he explained. However, because they carry the genetic expansion, “deleterious things” can already occur, he added.

 

Another focus included the ongoing study of brain tissue donated by deceased HD-affected individuals, known as post-mortem tissue. This “unbelievably technological marvel of investigations can then look literally cell by cell at those post-mortem brain sections,” Dr. Pacifici explained.

 

Vast data from Enroll-HD

 

Dr. Pacifici and I both wore caps from Enroll-HD, the global registry of more than 22,000 affected individuals and relatives.

 

CHDI runs Enroll-HD, which provides free data to companies seeking to develop therapies.

 

uniQure’s use of Enroll-HD data as an external comparison for AMT-130 clinical trial participants caused the FDA to oppose the company’s request for an accelerated drug approval.

 

Dr. Pacifici called Enroll-HD “one of the most remarkable prospective registry trials that's ever been run.”

 

The Therapeutics Conference included a presentation on Enroll-HD’s whole-genome-sequencing – mapping a person’s entire DNA – of nearly 20,000 of the people in its database. Announced a year ago, this project has already generated 450 terabytes of data.

 

It has revealed some crucial new clues about the genetics of HD onset: new discoveries about potential modifier genes that slow or hasten the start of the disease.

 

Scientists learn much about HD from studying so-called animal models of the disease, but, as Dr. Pacifici reminded me, only humans actually get HD.

 

Enroll-HD safely and non-invasively collects people’s blood, semen, tears, cerebrospinal fluid and DNA and tracks their symptoms, Dr. Padcific said. Enroll-HD thus helps to answer the big question of “how the disease manifests itself in people” over time and how their individual genetics influence the disease.

 

People’s participation in Enroll-HD “makes a huge difference,” Dr. Pacifici observed, adding that the program is positioned to prepare for future research needs as the field evolves.

 

The ‘urgent necessity’ for a therapy

 

On March 5 Amy Gray, the president and CEO of the Huntington's Disease Society of America e-mailed the HD community an update on the controversy involving the FDA, AMT-130, and Enroll-HD.

 

Gray noted the “urgent necessity” of a disease-modifying treatment. She recalled that Congress had directed the FDA to apply “‘regulatory flexibility’ for rare diseases – tailoring approaches when traditional trials are not feasible or would unduly delay access.”

 

Gray added that “innovative trial designs” such as Enroll-HD are appropriate when scientifically justified.

 

“We appreciate uniQure’s stated intent to continue engaging with the FDA,” Gray wrote.

 

Conquering HD

 

Like last year, the 2026 meeting had a session on “new enabling technologies and breakthrough science for neurodegenerative diseases.”

 

“The techniques that people are using would literally have been considered science fiction five years ago,” Dr. Pacifici said.

 

These included a bioengineered “mini-brain,” using actual human cells, that assembled all of the different broad classes of cell types in the brain, Dr. Pacifici explained.

 

The mini-brain was developed and presented at the conference by Alice Stanton, Ph.D., of Massachusetts General Hospital and Harvard Medical School.

 

“We're going to get her to now introduce cells that have the expanded gene and see how that changes so that we could do experiments in a dish instead of in the living organism,” Dr. Pacifici said. "We've got the best, the brightest doing-state-of-the art work."

 

To fill remaining “gaps” and “solve bottlenecks” on the way to therapies, yet more discoveries will be needed, he added.

 

With CHDI’s multi-million-dollar resources, the involvement of big companies, and the participation of HD families, “we’re going to conquer this thing,” Dr. Pacifici predicted.

 

 

Dr. Alice Stanton presenting her talk on her human "mini-brain" invention (above) and taking questions from the audience (below) (photos by Gene Veritas)