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.

My arduous, lucky, and enlightening journey since my mother’s death from Huntington’s disease 15 years ago

 

February 13, 2021, will mark fifteen years since my mother Carol Serbin died in 2006 after a two-decade fight against Huntington’s disease. She was 68.

 

Recalling her struggles and taking stock of my own predicament as an HD gene carrier have stirred me to reflect on my arduous, lucky, and enlightening journey since her death. Greater maturity and experience have also afforded me a deeper perspective on the HD cause as a whole.

 

My mother was diagnosed with HD in 1995, just two years after the discovery of the huntingtin gene. That breakthrough permitted the development of a genetic test confirming passage of the disease from one generation to the next. However, in retrospect, her symptoms probably had begun in the late 1980s, when she was in her late 40s.

 

The arduous years

 

Given Carol’s inexorable physical, cognitive, and emotional decline and the lack of treatments, in July 2005 my “HD warrior” caregiver father Paul Serbin sadly concluded that she needed 24/7 care in a nursing home.

 

Her move to the nursing facility greatly eased the caregiving burden on my father, although he faithfully visited her daily, still spoon-feeding her as he had done at home.

 

It also freed him to travel from their home state of Ohio to spend Thanksgiving of 2005 with my wife Regina, our five-year-old daughter Bianca, and me at our place in San Diego.

 

“I didn’t know how much I loved your mother until these past few years, taking care of her and seeing how much she has lost,” my usually stoic father confided in me.

 

Paul Serbin pushing Carol Serbin in wheelchair (photo by Gene Veritas, aka Kenneth P. Serbin)

 

From my standpoint, my mother was descending into an HD hell. Psychologically, this became the roughest period of my life. Not only was she was dying. I, too, had tested positive for the HD gene in 1999, so watching her decline was like “looking into the genetic mirror” that reflected my own future.

 

After my mother steadily lost the ability to swallow, in January 2006 I helped my father make the wrenching decision not to approve a feeding tube, which would at best have prolonged her physical life but left her bedridden, unable to communicate.

 

On the weekend of January 28-29, 2006, with my mother in hospice care at the nursing home, I flew to Ohio to visit her for what I knew could be the last time. With almost indescribable emotion, I said good-bye to my mother and, once again, gazed into the genetic mirror. This time it revealed a practically lifeless individual, barely able to move and unable to speak (click here to read more).

 

After that visit, and then learning that she had died in her sleep the morning of Monday, February 13, 2006, I felt utterly distraught about my gene-positive status.

 

In the months after her passing, I felt so terrified about getting HD that I began to act out some of the disease’s physical symptoms in front of my wife and daughter. I could not write anything in this blog for eight months.

 

My father, suffering his own severe cognitive loss likely accelerated by the loss of his wife, died on September 25, 2009, with a broken heart.

 

Tons of luck, and some positive strategies

 

I have now been without parents so long that memories of them feel like a distant past.

 

At 61, still without any apparent symptoms of HD, I feel extremely lucky. Each moment of good health is a blessing.

 

I have practiced personal and social enrichment, which scientists have recommended.

 

I have the benefit of a stable, good-paying job. Also, as the centrality of my parents faded, my roles as husband and father became paramount. Bianca became the center of our lives. Regina’s and Bianca’s love and support have proved crucial.

 

Also, because Bianca tested negative for HD in the womb, we have averted enormous health, financial, and psychological burdens (click here to read more).

 

The Serbin Family Team of the 2014 HDSA-San Diego Team Hope Walk: from left to right, Dory Bertics, Bianca Serbin, Jane Rappoport, Gary Boggs, Yi Sun, Kenneth Serbin, Regina Serbin, and Allan Rappoport (photo by Bob Walker)

 

I also exercise regularly, meditate daily, take medications to control depression and anxiety, and have a solid, long-term relationship with a psychotherapist.

 

I cannot be sure whether any of these things have staved off HD, but they generally bolster health.

 

Significantly, scientists have discovered very powerful explanations for why I am might have stayed asymptomatic so long: genetic factors, including modifier genes, that delay disease onset.

 

Gaining enlightenment about HD

 

Becoming enlightened about HD research and building bonds with scientists have reinforced both my advocacy and personal enrichment.

 

As a college professor, HD advocate, and explainer of the science ­– both in this blog and in interviews with researchers – I have had a privileged window on the quest for treatments. I have thoroughly enjoyed this work.

 

Moreover, I have gained great satisfaction in encouraging HD families to participate in research studies, platforms like Enroll-HD, and clinical trials.

 

Witnessing the progress towards treatments has also boosted my hope to participate someday in an HD clinical trial and, ultimately, enjoy the benefits of the first wave of effective treatments.

 

Overall, I believe that becoming enlightened about HD has helped me become a better person.

 

Pride

 

My devout Catholic parents – when I was a child, my father especially had hoped that I would become a priest – would have been especially proud of my family’s participation in #HDdennomore, Pope Francis’ special audience with the Huntington’s community in Rome in May 2017.

 

The pope declared HD to be “hidden no more” from the world.

 

I presented Pope Francis with a framed photo of my parents, well-dressed and smiling in a formal pose, taken after my mother had already been diagnosed with HD.

 

“My mother died of Huntington’s,” I told the Pope in his native tongue of Spanish. “My father cared for her for 20 years.”

 

In September 2017, I gave a presentation on #HDdennomore at my workplace, the University of San Diego. In February 2020, just before the COVID-19 crisis hit, I organized a screening of the poignant documentary on the papal audience, Dancing at the Vatican. It was well-attended by members of the local HD community.

 

Pope Francis displayed great love and mercy for our community.

 

Photo of Paul and Carol Serbin presented to Pope Francis by Kenneth Serbin, May 18, 2017. Photo taken shortly after Carol's diagnosis for Huntington's disease in 1995 (family photo).

 

Tributes, and imagining a world without HD

 

In many ways, since its inception sixteen years ago in January 2005, this blog has paid tribute to my parents. I have also honored the lives of other HD-affected people who valiantly fought against the disease such as Steve Topper and Harriet Hartl.

 

In these years since my mother’s departure, I have often wondered what our lives would have been like without the scourge of HD. This April 30, my mother would have turned 84 – within a plausible lifespan nowadays.

 

How wonderful it would have been had my mother – who could not interact with Bianca as a baby and toddler – been able to see her granddaughter reach college and to see Regina and me next year mark 30 years of marriage.

 

I can forge the greatest of tributes to my parents by continuing to nurture my health and hopefully secure a longer life so that I can grow old with Regina and see Bianca go out into the world.

 

When we learned of my mother’s diagnosis in 1995, there was no real hope of an HD treatment. However, since her death, research and the advent of clinical trials have brought unprecedented hope. As we’ve seen in response to the coronavirus pandemic, science can make great strides.

 

In unison with others, I can honor my parents by renewing the fight for Huntington's treatments so that thousands of families around the world can be freed from witnessing loved ones die early deaths.

Join the Facebook Live event (soon!) on Pope Francis’s historic audience with Huntington’s disease families

I want to invite the Huntington’s disease community – and all potential new supporters of the cause – to participate in my Facebook Live interview about Pope Francis’s historic HD audience on Wednesday, May 31, at 11 a.m. Pacific Daylight Time.

Conducted by San Diego Union-Tribune reporter Bradley Fikes, the interview will take place at this link: j.mp/sdutface. Participants can send questions and comments.

The interview will discuss details of the papal audience, where Francis declared that HD should be “hidden no more.” It will also allow for reflection on the significance of the event for the HD movement. (Click here to watch highlights of the audience).

Building on #HDdennomore’s goal of increasing global awareness of HD and removing the shame associated with the disease, we in the HD community can use the interview to expand our base of supporters.

Please invite others beyond your regular circle of friends, relatives, and acquaintances to watch.

Gene Veritas (aka Kenneth P. Serbin) with Pope Francis, who is holding a picture of Gene's late mother Carol Serbin, a victim of HD, and her long-time caregiver, the late Paul Serbin (photo by L'Osservatore Romano)

Pope Francis declares: Huntington’s disease should be ‘hidden no more’

Wow! In a stirring speech at the Vatican transmitted globally, Pope Francis declared to the world on May 18 that Huntington’s disease should be “hidden no more!”

“It is not simply a slogan, so much as a commitment that we all must foster,” the head of the Catholic Church said of the idea embraced by the roughly 1,500 HD family members and supporters gathered at the Paul VI Audience Hall just a few yards from St. Peter’s Square. They had gathered for "HDdennomore: Pope Francis's Special Audience with the Huntington's Disease Community in Solidarity with South America."

“The strength and conviction with which we pronounce these words derive precisely from what Jesus himself taught us,” the pope continued in Italian, as Spanish and English speakers listened to a simultaneous translation on headsets. “Throughout his ministry, he met many sick people; he took on their suffering; he tore down the walls of stigma and of marginalization that prevented so many of them from feeling respected and loved.”

Click here to read the full text of the speech in English.

After the speech, the highly popular and charismatic Pope Francis stopped to greet, hug, kiss, console, and have selfies taken with about 300 HD family members, HD researchers, pharmaceutical company representatives, and dignitaries seated in the front rows of the auditorium.

Overtaken with the pope’s powerful presence, some people cried uncontrollably as he stood before them.

The emotional charge traveled across the crowd. I welled up with tears as he got closer to my family and me in the third row.

After greeting my wife Regina and daughter Bianca and putting his hands on the head of my 78-year-old mother-in-law Lourdes, Pope Francis arrived at my place.

As I had planned, I showed the pope a picture of my mother Carol Serbin and father Paul Serbin, well-dressed and smiling in a formal pose, a photo taken after she had already been diagnosed with HD.

“My mother died of Huntington’s,” I told the Pope in his native tongue of Spanish. “My father cared for her for twenty years.”

I gave Francis a copy of each of my main books on the history of the Church in Brazil, explaining the theme of each with a brief phrase: priestly training and the Church’s struggle against the dictatorship in Brazil. I knew the themes were dear to him as the leader of the world’s Catholic clergy, respected colleague of Brazilian Catholic leaders and their flocks, and untiring proponent of social justice.

Francis said nothing, but he looked me in the eyes.

Somehow, my hands were now firmly holding the pope’s, and I told him: “Many thanks for supporting our community!”

Gene Veritas (aka Kenneth P. Serbin) with Pope Francis, May 18, 2017. In foreground, with back to camera, Bianca Serbin (photos by Regina Serbin).

Then Francis moved on to the next person.

When he finished circulating among the people, Francis returned to the stage, looked back at us and waved, and then exited with his papal entourage.

After listening to some closing music by performers from HD families, we filed out of the auditorium.

As I wrote in a blog note my cell phone, I felt “drunk with excitement” as I left with my family, hugging and taking a selfie with event co-organizer and HD global advocate Charles Sabine, greeting fellow advocates from South America, and at one point becoming disoriented and nearly tumbling to the ground. Regina became concerned that I would injure myself.

We had done it! We had witnessed Pope Francis decisively place Huntington’s disease on the world agenda.

Above, the audience at the May 18, 2017, papal audience on Huntington's disease. Below, Gene Veritas and Charles Sabine (photos by Gene Veritas).

(Click here to watch the audience on the Vatican’s YouTube channel. In my next article I will comment further on Francis’s HD speech and explore in detail the event and its impact.)

(My trip to Rome was made possible by the College of Arts and Sciences, the Frances G. Harpst Center for Catholic Thought and Culture, the International Center, and the Department of History of the University of San Diego. I am grateful for the institutional and moral support of my colleagues and students.)