As uniQure seeks to overcome ‘dysfunction’ at the FDA, Huntington’s disease community rallies in defense of gene therapy drug

As uniQure seeks to overcome a decision by the U.S. Food and Drug Administration (FDA) to roll back its consultations regarding the firm’s promising gene therapy for Huntington’s disease, the HD 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.

 

In September uniQure announced that its drug, AMT-130, had slowed the progression of HD by 75 percent over three years.

 

On November 3, uniQure announced that, after a recent meeting with the FDA, it believes that the “FDA currently no longer agrees” that data from its clinical trial of AMT-130 "may be adequate to provide the primary evidence in support of” an application for approval.

 

The company’s plan to seek approval of AMT-130 in early 2026 and launch it into the market later that year may no longer be possible.

 

Although the FDA claims it will “unleash gene therapies,” the documented collapse of the agency under the Trump administration, a more conservative view of gene therapies, and “mistrust and paranoia” in the division in charge of those therapies set the stage for backtracking on AMT-130 (click here to read more).

 

On November 13, the key biotech site 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, wrote me via e-mail on November 14. “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 company is withholding further public comment until it receives official final minutes of its most recent meeting with the FDA.

Two groups of HD advocates have launched petitions to the FDA to support the original uniQure timeline for AMT-130. They are discussed below.

 

 

The online petition to the FDA titled "Bring Hope to Huntington's Disease Families," on November 15, 2025 (screenshot by Gene Veritas, aka Kenneth P. Serbin)

 

Deep frustration with the FDA

 

The STAT report noted that Kapusta “doesn’t like all the drama” inside the FDA surrounding its upending of uniQure’s plans. They had involved extensive consultations with the FDA in 2024.

 

Aiming to stabilize the agency, the FDA has named Richard Pazdur, M.D., a leading cancer specialist and 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, as reported by STAT.

 

According to the STAT report, 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 the STAT reporter.

 

Meanwhile, the FDA and some scientists have moved ahead with researching and approving the world’s first personalized gene-editing treatments for individuals with rare genetic conditions. It is unclear how much this might benefit rare disease communities like HD (with thousands of affected individuals) and impact the FDA’s thinking on AMT-130.

 

Two petitions: ‘AMT-130 could change everything’

 

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.

 

One petition is titled “Bring Hope to Huntington's Disease Families: Urge the FDA to Uphold Accelerated Approval.”

 

It is sponsored by the Huntington’s Disease Society of America, HD Reach, Help4HD International, Huntington’s Disease Foundation, and Huntington’s Disease Youth Organization. These organizations have also pledged to improve collaboration.

 

It notes that “the FDA is now wavering on its commitment” to AMT-130. It asks the agency to honor its previous guidance to uniQure, recognize the urgency of the unmet dire medical need of HD families, and to expedite the approval of AMT-130.

 

It urges people to sign: “We cannot allow procedural hesitation to become a death sentence.”

 

The other petition is titled “Accelerate Breakthrough Drug Approval for Huntington's Disease - UniQure AMT-130.”

 

“Our Plea: Turn Heartbreak Into Hope,” it states. “We are mothers and fathers, sons and daughters, brothers and sisters, husbands and wives, friends and caregivers – all united by love and by loss. AMT-130 could change everything.”

 

As an HD gene carrier and HD family member, I immediately signed the first petition upon learning about it. I urge all friends and supporters of the HD community to join us in our plea to the FDA.

Understanding the FDA’s surprising step back on uniQure drug that slows Huntington’s disease

 

Less than six weeks after uniQure announced that its gene therapy drug slowed the progression of Huntington’s disease by 75 percent over three years, the U.S. Food and Drug Administration (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 of more than 22,200 people, as a baseline, rather than those taking a placebo, to compare with those on AMT-130. After extensive consultations with the FDA in 2024, uniQure had gotten permission from the agency to use the Enroll-HD data.

 

“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.”

 

uniQure expects to receive the final minutes of its meeting with the FDA within 30 days and plans to urgently interact with the agency “to find a path forward for the timely accelerated approval of AMT-130,” the press release continued.

 

“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 Matt Kapusta, the uniQure CEO. “This news is unexpected, and we are truly disappointed for people living with HD, who have no disease-modifying treatment options for this devastating disease.”

 

Kapusta added that “we strongly believe that AMT-130 has the potential to bring substantial benefit to patients, and we remain fully committed to working with the FDA to determine the best path forward to rapidly bring AMT-130 to patients and their families in the U.S.”

 

 

David Margolin, M.D., Ph.D., uniQure's vice president for clinical development, presents data illustrating AMT-130's slowing of the progression in Huntington's disease at the 20th Annual HD Therapeutics Conference, Palm Springs, CA, February 25, 2025 (photo by Gene Veritas, aka Kenneth P. Serbin).

 

FDA claims to ‘unleash gene therapies’

 

The October 30 Huntington’s Disease Society of America (HDSA) webinar on AMT-130, featuring uniQure’s chief medical officer, Walid Abi-Saab, M.D., offered no inkling of the FDA’s new position.

 

Some 1,000 people attended the webinar – a sign of the excitement about AMT-130 in the HD community. Reuniting after 17 years of estrangement, my own family has found great hope in the possibility of this treatment, though we understand that the drug is not a cure and might not even reach the public.

 

The FDA so far has provided no comment to the media on the matter. At the top of its website’s homepage it has the phrase “first six months of FDA reforms,” including “unleashing cell and gene therapies.”

 

As this blog reported in July, under the Trump administration the uncertainty of public funding for science has created serious challenges to HD research.

 

Politics and society play a role

 

Science and medicine do not act in a vacuum and are impacted by politics and society, as HD family member and historian Alice Wexler brilliantly illustrated in her book The Woman Who Walked into the Sea: Huntington’s and the Making of a Genetic Disease (click here to read my review).

 

In July, a New York Times report titled “Inside the Collapse of the FDA” detailed how Health and Human Services Secretary Robert F. Kennedy Jr., is “dismantling the agency.”

 

The key biotech and life sciences website 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.”

 

Dr. Prasad heads the Center for Biologics Evaluation and Research.

 

Only last week STAT reported that a “slow-boiling feud” between Dr. Prasad and his staff “is threatening the future of the center that regulates the nation’s vaccines, biological products, and blood supply.”

 

According to the report, officials in the center described it as “rife with mistrust and paranoia” and with fears of “retaliation” for pushing back on Dr. Prasad. The center has lost hundreds of employees this year to retirements, layoffs, and resignations. Dr. Prasad has also pushed out senior leaders, including “top cell and gene therapy regulators,” STAT reported.

 

Prasad has also played a role in limiting access to Covid-19 vaccines, according to STAT and the New York Times.

 

The HD community is ‘highly mobilized’

 

The scientist-written website HDBuzz noted that, although “the reason for the change of heart” of the FDA is “not currently clear,” “it makes the timeline for advancing AMT-130 less clear, with additional uncertainty as the U.S. government shutdown continues.”

 

“The decision by the FDA to not agree that an external control group can be used to apply for a [drug application] doesn’t change the data” of AMT-130’s actual effect in the clinical trial run by uniQure, HDBuzz stated. It simply means that the FDA would want to see more data, possibly from a trial designed with a placebo control group, before moving forward with a BLA for AMT-130.

 

HDBuzz also noted that uniQure is working with the equivalent of the FDA in the United Kingdom and Europe, with an approval there possibly leading to acceptance elsewhere.

 

HDBuzz stated that “we push forward – together.”

 

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 Huntington’s disease (HD) patient and family organizations are more critical now than ever.” The four are Huntington’s Disease Foundation (formerly Hereditary Disease Foundation), HD Reach, Help4HD International, and Huntington’s Disease Youth Organization.  

 

“The next steps here are uncertain,” the brokerage and investment banking firm Stifel wrote, “but given the highly mobilized patient community in Huntington’s, and other external political forces that may have influence on the agency, the story here may not be over.”

As hopes build about the first effective therapy, a Huntington’s disease family reunites

 

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 unrelated to HD that led me to step back from HD advocacy, including this blog.

 

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. Despite her HD, we had an understandable conversation. 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. Since then, we have texted each other regularly.

 

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 at a restaurant in Painesville. 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. I thanked Donna, Barry, and Greg for forming a team in the annual Huntington’s Disease Society of America Hope Walk (HDSA) fundraiser.

 

I have their permission to write this article.

 

Left to right, Gene Veritas (aka Kenneth P. Serbin), Donna, Barry, Greg, and Regina. Barry is wearing an HDSA Team Hope t-shirt (personal photo).

 

A family reunion – and wonderful news!

 

We all caught up on one another’s lives.

 

I squeezed Donna’s hand firmly several times and looked into her eyes. Because of HD, she had to retire from her job, and recently she stopped driving.

 

Barry, always the dedicated husband and now a caregiver, detailed the adaptations he had made in their ranch house because of Donna’s involuntary movements and instability in walking. She had five falls in their previous, two-story home.

 

As I had remembered him as a child and young adult, Greg was ebullient, enthusiastically speaking of his work as a computer programmer, his car, and his fiancé. He does not have HD symptoms.

 

We also discussed potential HD disease-modifying treatments – slowing, halting, or reversing the progression of symptoms.

 

I especially had in mind uniQure’s AMT-130, about which I had seen a presentation at the 20th Annual HD Therapeutics Conference in February in February. The uniQure program seemed the closest to seeking approval for its drug from the U.S. Food and Drug and Administration (FDA).

 

Since our dinner, we have stayed in touch.

 

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!” Donna and Greg both responded, echoing the elation of HD scientists and HD families.

 

I hope that we can continue to rebuild our lost family ties and support one another in the fight against HD, as we once did at the start of our HD journey with my mother’s diagnosis in 1995.

 

Rescuing neurons from death

 

HD occurs because of the massive death of brain cells (neurons).

 

AMT-130 is the first successful disease-modifying HD drug. In the uniQure clinical trial, it achieved its main goal and demonstrated a 75 percent slowing in the progression of the disease over a three-year period.

 

On September 25, Ed Wild, M.D.,Ph.D., a professor of neurology at University College London and an investigator on the uniQure program and senior advisor to the company, gave a podcast interview to HD gene carrier Lauren Holder of Help4HD International.

 

Dr. Wild pointed out that “AMT” refers to uniQure’s original name: Amsterdam Molecular Therapeutics. The Dutch and American company was founded in 1998.

 

Because it is a gene therapy, AMT-130 remains in the body permanently, thus allowing for the running of long clinical trials and without the drawback of a possible placebo effect, Dr. Wild explained. The effect of the drug “appears to be growing” over time, he added.

 

The 75-percent improvement went “dramatically beyond what any one of us could have dreamed of,” he said, adding that cognitive decline also slowed substantially.

 

AMT-130’s effectiveness lies in its reduction of the abnormal huntingtin protein in the brain.

 

Dr. Wild observed that the slowing of the disease has resulted from AMT-130’s “rescuing neurons” from death.

 

Because AMT-130 mainly targets the striatum (deep in the brain), other areas such as the cortex might still need treatment, perhaps done with another type of drug in a combination therapy, Dr. Wild observed.

 

He added that additional studies of the drug might be needed. “We’re up for all of that,” he said. “It’s putting flesh on the bones of what is already a winning recipe.”

 

Important details to be resolved

 

Many important details must be resolved before AMT-130 reaches HD patients.

 

In early 2026, uniQure plans to apply to the FDA for drug approval. Pending approval, the drug would be launched in the U.S. later in 2026. uniQure would need to gear up its AMT-130 operations to coordinate with HDSA and other patient and clinical organizations to inform the HD community about the drug and its availability.

 

Administering AMT-130 is far more complex than the pills or spinal injections used in other clinical trial programs: it involves 12 to 18 hours of brain surgery.

 

Dr. Wild noted that the treatment will be “expensive.” “The drug is made from a virus and so it has to be manufactured in specialized facilities,” he explained.

 

Dr. Wild estimated that, based on previous gene therapies, AMT-130 will cost $2 million per person.

 

“It’s obviously a lot of money, but we’re already spending a lot of money to keep people with Huntington’s cared for, to manage the symptoms, to provide assistance to their families,” he noted. The insurance industry, he said, also will need to agree to pay for the treatment.

 

Waiting for news of who can be treated

 

While the AMT-130 clinical trial included people in stages 2 and 3 of the disease (stage 4 being the worst), “it’s difficult to predict” who would get the treatment of an approved drug, Dr. Wild explained. He said the community needs to have the FDA permit as broad a label as possible: simply “Huntington’s disease.”

 

That label would allow people (like Greg and me) who have tested positive for the HD gene but lack visible symptoms to obtain the treatment. HD research has determined the disease process begins at birth, with the damage building over life, Dr. Wild observed. Gene therapy, a one-and-done treatment, is most potent when done early in life, he added.

 

Because of the conditions of accelerated approval granted by the FDA, uniQure would need to continue monitoring the drug, Dr. Wild said. If the drug does not work, approval can be removed.

 

A critique of AMT-130 and a call for accurate communication

 

Not everyone shares the same enthusiasm for AMT-130. Ignacio Muñoz-Sanjuán, Ph.D., the CEO of Rumi Scientific, a drug discovery company focused on genetic and neurological diseases, published a critique of uniQure’s AMT-130 data (click here to read more).

 

A native of Spain, Dr. Muñoz co-founded Factor-H, a charitable organization seeking to assist poor HD families in Latin America and raise awareness about their plight. He is the former vice president of translational biology for CHDI Foundation, Inc., the largest private funder of HD research and the sponsor of the annual HD Therapeutics Conference.

 

Dr. Muñoz agrees that the AMT-130 results are “a turning point for the field of HD and, more broadly, for the treatment of neurodegenerative conditions at large.”

 

However, Dr. Muñoz raised caveats about AMT-130. He wrote, for instance, that the study “only showed the results derived from 12 patients who have completed the full 36-month period” of the trial and they were “in the early stages” of the disease.

 

Dr. Muñoz urged uniQure to analyze data from “all individuals in the study.” With the “small number of individuals receiving the therapy, one or two people could be disproportionately contributing to the signals of protection demonstrated for the group average.” Twenty-nine volunteers took part.

 

“Families deserve a realistic sense of the commercial path ahead,” Dr. Muñoz added, advising “careful communication” with HD families. Access will “dominate the conversation,” he added, noting that “costs, geography, and the need for specialized neurosurgical centers will slow availability, creating disparities that will frustrate many families worldwide. The path to broad applicability will be slow and difficult.”

 

‘Day one of a new world’

 

I wish my parents, Paul and Carol Serbin, were still alive to witness this moment in the HD journey! An “HD warrior,” my father was my mother’s HD caregiver for over ten years.

 

Paul and Carol Serbin (family photo)

 

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.

 

As my blog has documented the past 20-plus years, HD families face enormous stigma and tensions. I am overjoyed at my family’s rapprochement at this promising moment.

 

As Dr. Wild noted, before AMT-130 more than HD 100 clinical trials had been run, without disease modification.

 

“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,” including, he said, poor HD families in Venezuela who contributed blood samples in the search for the huntingtin gene.

 

“No one is free until everyone is free,” he said.

Wonderful news: uniQure’s one-and-done drug slows Huntington’s disease

 

AMT-130, a one-time gene therapy developed by uniQure, has successfully slowed the progression of Huntington’s disease.

 

While that is not a cure, and the therapeutic process is hardly simple, it is the first evidence that scientific progress translates into meaningful results for those suffering from HD.

 

The treatment is far more complex than a pill: it involves 12 to 18 hours of delicate brain surgery. A neurosurgeon injects AMT-130 directly into the brain under the guidance of an MRI. As a gene therapy, AMT-130 requires just this one application. (Watch the uniQure video about how AMT-130 is administered here).

 

According to clinical trial results reported by uniQure on September 24, AMT-130 achieved its main goal (primary endpoint) and 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 release stated. TFC is total functional capacity. It refers to a person’s ability to function – a key loss in HD.

 

Other progress

 

The company, based in Lexington, MA, and Amsterdam, 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 second measures of motor (movement) and cognitive function, the release stated. Movement disorders and cognitive loss are major HD symptoms. 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,” Sarah Tabrizi, M.D., Ph.D., a leading HD specialist at University College London, 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.”

 

 

David Margolin, M.D., Ph.D., uniQure's vice president for clinical development, presents data illustrating ATM-130's slowing of the progression in Huntington's disease at the 20th Annual HD Therapeutics Conference, Palm Springs, CA, February 25, 2025 (photo by Gene Veritas, aka Kenneth P. Serbin).

 

Transforming the HD landscape

 

AMT-130 seeks to lower the amount of harmful mutant huntingtin protein in the brain cells of patients. Whether the drug has actually done this has yet to be verified.

 

In early 2026, uniQure plans to apply to the U.S. Food and Drug Administration (FDA) for drug approval. Pending drug approval, the drug would be launched in the U.S. later in 2026.

 

“We are incredibly excited about these topline results and what they may represent for individuals and families affected by Huntington’s disease,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders.”

 

Hopes for a life-long treatment

 

“This is the first time any drug has been shown to alter the course of HD in people in a clinical trial,” the scientist-written website HDBuzz stated. “uniQure believes that AMT-130 has the potential to be a treatment that lasts for life.”

 

uniQure officials told HDBuzz that, beyond the FDA, they plan to seek approval with other regulators, including the European Medicines Agency, which oversee drug approvals in Europe.

 

HDBuzz cautioned that key details need to be worked out before AMT-130 can be administered to a large group of people beyond the fewer than 30 people whose data were analyzed by uniQure.

 

Only some of those individuals received the high dose of the drug that proved effective. Also, because AMT-130 requires an operation, the company must find a way to provide access to the drug, and at an affordable level, to a larger number of people.

 

On the whole, despite the caveats and complexities, this is wonderful news for the HD community.

 

"We never in our wildest dreams would have expected a 75% slowing of clinical progression," Dr. Tabrizi told the BBC.

Brain donation programs – now perhaps at risk of losing funding – are key to a Huntington's disease cure: a family's story

 

In July 2022 Dorlue Schulte of San Diego died at home after a long struggle with Huntington’s disease. To benefit HD research, Dorlue donated her brain to the Harvard Brain Tissue Resource Center (HBTRC) at the nonprofit McLean Hospital in suburban Boston.

 

“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 in a presentation last October at the Huntington’s Disease Society of America (HDSA) San Diego chapter’s “Family is Everything” Education Day.

Doug observed that HD researchers are “coming up with great ways to inspect the brain to learn from them.”

 

Dorlue Schulte (family photo)

 

“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.”

 

For his outstanding advocacy Doug received the 2021 Woody Guthrie Award at the HDSA national convention. He served on the HDSA-San Diego board from 2019-2022. A retired firefighter, Doug has raised awareness about HD among police officers to make them “a friend, not a foe,” when encountering affected individuals.

 

You can watch Doug’s 30-minute talk in the video below.

 

 

‘Precious’ human data

 

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 of Robert Pacifici, Ph.D., the chief scientific officer of the key, HD-focused CHDI Foundation, Inc.

 

At meetings like CHDI’s Annual HD Therapeutic Conference scientists discuss the growing body of knowledge coming from these brains.

 

Doug was inspired to present Dorlue’s story in part by Dr. Pacifici’s statements about the importance of research in humans. Although the huntingtin gene exists in many species, only humans develop HD.

 

Over 10,000 brains collected

 

Founded in 1978 and one of the first brain banks in the U.S., Harvard Brain Tissue Resource Center is one of six repositories that are part of the federal National Institutes of Health (NIH) NeuroBioBank, a centralized resource for the collection and distribution of human brain specimens for research.

  

According to the HBTRC website, it has collected over 10,000 brain donations from across the U.S. and distributed over a hundred thousand samples, both nationally and globally, that have resulted in hundreds of publications. More than 45 different brain disorders are represented in the HBTRC collection, including HD.

 

HDSA endorses HBTRC. The two have a long-standing collaboration, and HBTRC has one of the largest collections of brains donated by persons diagnosed with HD in the U.S. if not the world.

 

The HBTRC’s home, McLean Hospital, is the largest psychiatric teaching hospital of Harvard Medical School.

 

The sole funder of the HBTRC is the federal NIH, HBTRC director Sabina Berretta, M.D., wrote in an e-mail interview with me on July 25. An associate professor of psychiatry at Harvard Medical School, she carries out HD research on the team of investigator Steve McCarroll, Ph.D., whose lab has created precise techniques for measuring the impact of HD on single brain cells.

 

As Doug pointed out, this type of research is only possible because of brain donations.

 

The uncertainty of future public funding

 

Harvard University has sued the federal government to try to block the Trump administration’s freezing of nearly $3 billion in research funds. The government also seeks to eliminate $783 million in NIH funding.

 

A statement on the NeuroBioBank website reads: “This repository is under review for potential modification in compliance with Administration directives.”

 

Responding to my questions about this situation, Dr. Berretta wrote that the cuts at Harvard and the NIH have not currently impacted the HBTRC. The government has not flagged current funds, she added. She noted, however, that “we are not sure at the moment” about potential restrictions arising from government concerns about diversity, equity, and inclusion. 

 

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.”

 

Dr. Berretta explained that “the current funding uncertainty creates some challenges, particularly for talent retention and long-term planning, both critical to our work.”

 

“The other 5 brain banks part of the NIH NeuroBioBank are in our same situation,” she added.

 

Dr. Sabina Berretta (McLean Hospital photo)

 

A family discussion and a decision

 

Dorlue was 63 and had been married to Doug for 32 years. After graduating from high school in 1976, she worked for 20 years in a Pacific Bell office. She volunteered at her church, participated in her son Ryan’s school PTA, and enjoyed family camping trips. As a young adult, Ryan tested negative for the HD gene.

 

Dorlue was remembered as having “a fighting spirit that never wavered in the face of her diagnosis” with HD, including participation in clinical trials in hopes of a cure.

 

Doug and Dorlue discussed, and then agreed to, donating her brain when she was no longer in “denial” about her disease and learning that Ryan was now free of the disease, Doug said in his presentation. Dorlue registered for the donation in 2012.

 

“It should be your decision and no one else’s,” Doug emphasized, noting that contemplating a donation can be “very stressful” because of all of the difficulties already involved in HD.

 

The decision must involve the person’s legal first of kin, who will see through the donation after the person has died.

 

There are many reasons to donate – or not donate, said Doug, noting that some might have religious reasons against the process.

 

He recommended that families start conversations about donations “early.”

 

“You can cancel at any time,” he said of the process. The opportunity to donate is “a blessing,” he added.

 

A ‘very professional’ organization

 

A person can pre-register their donation on the HBTRC website or register any time over the phone, even after an individual has died, Doug explained.

 

Doug spoke several times with Dr. Berretta.

 

“She’s very compassionate,” he said. “The organization is very professional. I really felt that they understood how difficult it was to go through that process, especially right after your loved one died.”

 

Doug noted several exclusionary criteria that might prevent a brain from being accepted, such as a delay of more than 24 hours in getting the brain to the bank; a stroke or penetrating head injury; or testing positive for HIV, hepatitis B, or hepatitis C.

 

Although “it costs a lot of money for the brain to be put on a plane and sent to Harvard,” the only charges covered by the family are the usual funeral costs, such as cremation or embalming, Doug said.

 

Just 24 hours to get the brain delivered

 

The 24-hour clock for the donation to be received starts at the moment the last person saw the deceased alive, Doug continued.

 

Dorlue died at 6 a.m., when a hospice nurse declared her dead. Doug contacted the funeral home, which needed to transport the body to the facility that “harvests” the brain. The funeral home worker took four hours to arrive, Doug said.

 

“We were ten hours into this before they even took the body out of the house,” he recalled. “I was pretty anxious that we get this thing off.”

 

The brain is packed in ice for transport and placed in the luggage area of the plane so that it stays cold throughout the flight, Doug explained.

Once it arrives at the HBTRC laboratories, the brain is immediately dissected. Part of it is immediately frozen and kept at minus 80 degrees centrigrade. Another part is immersed in formalin. It is then assessed by a neuropathologist, who generates a neuropathology report. Both preparations are made available to investigators.

 

Once the brain arrived at Harvard, Doug received a call reassuring him that it had arrived undisturbed and on time. To preserve the integrity of the tissue for research, the brain is ultimately frozen at minus 80 degrees centigrade.

 

Doug also sent the HBTRC Dorlue’s medical records to assist in their research on her brain.

 

“That’s a big part of what the scientists look at,” he said. “They compare the brain with the symptoms and see if there’s any similarities or not.”

 

Crucial work towards a cure

 

The HBTRC website has an FAQ, donation forms, and phone numbers for making a donation.

 

This HBTRC does crucial work in the quest for a cure.

 

Doug has signed up to donate his brain. I will do the same.

 

As Doug put it, the bank collects brains from around the U.S. and sends samples around the world.

 

“Who knows who’s going to find a cure,” he said.