Bridging the Huntington’s and early onset Alzheimer’s disease communities: a report from a family conference

 

In the quest to conquer chronic illnesses, members of disease communities need to build solidarity and learn from one another. I explored this theme in a 2018 article about the fellowship

that a sufferer of type 1 diabetes and I, a gene carrier for Huntington’s disease, had built in our student-teacher relationship at the University of San Diego.

 

On July 30, the common challenge of the daunting search for therapies for neurodegenerative diseases hit home again as I participated in the eighth international DIAD Family Conference, held at the Hilton San Diego Bayfront hotel in downtown San Diego. DIAD stands for “dominantly inherited Alzheimer’s disease,” also known by other names, including early onset familial Alzheimer’s disease.

 

Late onset Alzheimer’s affects more than 5.8 million mainly elderly Americans but has no clear cause. In contrast, early onset Alzheimer’s ­– like Huntington’s – is a rare disease with a known genetic cause. Like HD, it strikes in the prime of life, when people as young as their twenties are affected.

 

Both HD and early onset Alzheimer’s are autosomal dominant conditions: carriers of a mutant gene will definitely develop the disease, and their children have a 50-50 chance of inheriting the disorder. In HD, the mutant huntingtin gene is the culprit. In early onset Alzheimer’s, one of three different mutations causes disease.

 

Early onset Alzheimer’s is rarer than HD. Approximately 41,000 individuals live with HD in the U.S. Globally, an estimated 45,000 people have early onset Alzheimer’s.

 

Sadly, as with HD, there is no treatment yet to arrest the progression of the disease.

 

As I learned at the conference, early onset Alzheimer’s, like HD, produces devastating, ultimately deadly symptoms mainly affecting a person’s memory and behavior. Common symptoms include: abnormal social behavior, agitation, confusion/disorientation, hallucinations, hypertonia (arms/legs are difficult to move/reduced flexibility), language impairment, dementia, Parkinsonism (movement abnormality: tremor, slow movement, muscle stiffness), seizures, and disinhibition.

 

 

Gene Veritas (aka Kenneth P. Serbin) at the 2022 DIAD Family Conference (photo by Gene Veritas)

 

Sharing insights with an Alzheimer’s researcher

 

I was invited to the DIAD Family Conference by Lindsay Hohsfield, Ph.D., co-founder of Youngtimers, a 501c3 nonprofit established in 2021 to promote education, support, and research for the early onset familial Alzheimer's community.

 

The group’s motto is: “we are too young to forget, too many to be forgotten.”

 

An Alzheimer’s researcher focusing on ways brain cells control inflammation, Dr. Hohsfield was inspired to enter the field after her father’s diagnosis with early onset Alzheimer’s. He died in his early 50s.

 

“When my father was sick, my family and I felt isolated and lost,” Dr. Hohsfield wrote in a letter on the organization’s website. “My hope is that with Youngtimers, no early onset familial Alzheimer’s patient and family will ever have to feel alone.”

 

Dr. Hohsfield has also explored the dilemma of “childbearing versus clinical trial participation” for Huntington’s and early onset Alzheimer’s families. Currently, pregnant women are excluded from clinical trials for those disorders. She calls for the establishment of a standard to address patient well-being and needs concerning this dilemma.

 

In May Dr. Hohsfield, a reader of this blog, interviewed me on Zoom about my article reflecting on the significant benefits of psychotherapy in my fight against Huntington’s. That article sparked a discussion in the early Alzheimer’s community about finding a life coach/mind coach to help cope with testing positive for that disorder and living life to the fullest. The interview with Dr. Hohsfield will be posted on the Youngtimers’ website.

 

Facilitating support sessions

 

Dr. Hohsfield and the conference organizers invited me to facilitate two one-hour drop-in support sessions for members of early onset Alzheimer’s families. Leveraging my long experience as an HD gene carrier and advocate, I was assigned to a table discussing “post genetic testing: coping with risk and how it changes over time.”

 

Other tables covered grief, communication, living with symptoms, and “catching your breath.”

 

In all, about a dozen people came to my table over the two hours. Usually, rather than having me facilitate, we exchanged ideas about genetic testing, prenatal testing, workplace confidentiality about our genetic status, securing insurance coverage, and more. 

 

The "post genetic testing" support sign at the 2022 DIAD Family Conference (photo by Gene Veritas)

 

The most poignant moment came when three members of an affected family asked how to navigate tensions in the extended family over the onset of symptoms one of them had suffered. That individual, having stopped being a breadwinner, needed medical care and caregiving.

 

This went beyond the scope of genetic testing, so I relied on memories of similar predicaments at my local HD support group. The other members of the group and I provided a sounding board for this family, encouraging them to use the resources offered by Youngtimers and seek out local support.

 

At these sessions all of us quickly bonded. We found comfort in our shared plight: facing a devastating neurological disorder.

 

Framing HD in a broader light

 

The DIAD Family Conference was sponsored by the Dominantly Inherited Alzheimer Network Trials Unit, the Alzheimer’s Association, and the National Institute on Aging. It was held in conjunction with the Alzheimer’s Association International Congress, July 31-August 4, in San Diego.

 

In between several moving family presentations to the nearly 200 attendees, the audience heard updates from Alzheimer’s physicians and researchers on the progress of research, including ongoing global clinical trials to prevent the disorder.

 

As I have witnessed at Huntington’s conferences, the Alzheimer’s scientists pointed out that research advances have brought the field to an unprecedented moment in the search for treatments. Leading Alzheimer’s researcher Randall Bateman, M.D., stated that it is a question of not “if” but “when” effective therapies become available.

 

After the conference, I met with Jason Karlawish, M.D., a University of Pennsylvania specialist on late onset Alzheimer’s and the author of the key 2021 book The Problem of Alzheimer’s: How Science, Culture, and Politics Turned a Rare Disease into a Crisis and What We Can Do About It.

 

This book has helped me frame my efforts to understand the history of the HD cause in a broader, comparative light.

 

A deeply personal and fulfilling introduction

 

My participation in the DIAD Family Conference will help me to understand the strengths and weaknesses of the Huntington’s movement in comparison with others facing similar challenges. I hope that, however modestly, it helps point the way towards increased collaboration in the quest for therapies.

 

I look forward to learning more about early onset familial Alzheimer’s disease, its causes, and symptoms.

 

I was moved by the many stories of struggle, but also humor and optimism, from affected individuals and their families.

 

After this deeply personal and fulfilling introduction to the early onset Alzheimer’s community, I felt energized.

 

I look forward to when both communities can celebrate the discovery of therapies.

With the constitutional right to abortion gone, an uncertain medical future for Huntington’s disease families

With the U.S. Supreme Court’s radical toppling of long-standing abortion rights on June 24, families affected by Huntington’s disease and thousands of other rare and neurological disorders face a profoundly uncertain future regarding medical care in the United States.

 

The majority opinion in the 5-4 decision overturned the 1973 Roe v. Wade ruling, which was reaffirmed in the 1992 Planned Parenthood v. Casey decision. Those previous rulings guaranteed a woman’s right to an abortion before viability of the fetus.

 

Now, the authority to regulate abortion has been returned to Congress and the states. The court voted 6-3 in Dobbs v. Jackson Women’s Health, confirming a Mississippi ban on most abortions after fifteen weeks of pregnancy.

 

The majority position held that the Constitution does not confer a right to abortion.

 

Complicating a heart-wrenching situation

 

HD families have relied on prenatal genetic testing and abortion to prevent passing on the genetic mutation to their children. My mother died of HD in 2006, and I tested positive for the mutation in 1999.

 

In 2000, our gestating daughter tested negative for HD in the womb, forestalling the need for us to consider abortion. She just graduated from college.

 

Sadly, many families have lost children to juvenile HD (JHD).

 

Now, access to abortion will disappear or be severely restricted in almost two dozen states.

 

“This complicates an already incredibly difficult and heart-wrenching situation for women affected by HD,” leading advocate Lauren Holder wrote me in a Facebook message regarding the abortion ruling. An HD gene carrier, Holder has one at-risk child, and other who tested negative during the pregnancy. She lost her father Stephen Rose, Jr., 62, to HD last year.

 

“If I could recommend one thing, it would be to not let [our reaction] stand as just a sad or irate post on social media,” Holder urged. “If we want this to change, we have to be willing to speak up and advocate for ourselves, for women’s rights, at the state level now.”

 

Lauren Holder (left) with her late father Stephen Rose, Jr., who died of HD in 2021 (personal photo)

 

HD sheds light on bioethical challenges

 

As I reported in 2011 (click here and here), controversy over abortion in the HD community reflects the national societal divide.

 

However, confronting HD’s devastating symptoms and stigma, our community’s early and deep experience with genetic and prenatal testing, preimplantation genetic diagnosis (PGD), suicide, assisted suicide, euthanasia, disability legislation, mistreatment by the police, a crushing caregiving burden, and other challenges have made us bioethical pioneers.

 

Those issues include human embryonic stem cell research, crucial for developing a greater understanding of HD and potential therapies. I commented on religious leaders’ concern about the research in a September 2017 presentation on Pope Francis’s historic meeting the previous May with the HD community in Rome, where he declared HD to be “hidden no more.” My family and I attended.

 

Francis had encouraged the HD scientists present to avoid research involving human embryos, “inevitably causing their destruction.”

 

“Bioethicists, both within and without the [Catholic] Church, can learn from the HD community,” I asserted. “This is not an easy issue, but it requires dialogue. Unfortunately, some media outlets focused on this aspect of the meeting, ignoring the historic moment and how Francis exuded love towards us in the HD community.”

 

Defenders of the sanctity of human embryos continue to support a ban on this research.

 

Some abortion opponents have also proposed that embryos have legal status as persons.

 

PGD in jeopardy?

 

The blistering Supreme Court dissenting opinion by the three liberal justices described the decision as “catastrophic,” taking away women’s freedoms, threatening other rights, and eroding the court’s credibility.

 

Because of the majority’s position, the dissenting justices affirmed that the Supreme Court will “surely face critical questions” about how the ruling will be implemented.

 

“Further, the Court may face questions about the application of abortion regulations to medical care most people view as quite different from abortion,” the dissenting justices wrote. “What about the morning-after pill? IUDs? In vitro fertilization?”

 

Earlier this month, in anticipation of the expected overturn of the right to abortion, HD advocate Allie LaForce recognized that changes in the laws in some states might lead her and her untested, at-risk husband, Minnesota Twins baseball pitcher Joe Smith, to change their approach to assisting families with PGD through their foundation, HelpCureHD. PGD involves in vitro fertilization. LaForce is currently pregnant after using PGD.

 

LaForce and Smith have considered the possibility of paying for families to travel out of state for PGD if they live in a place that has restricted the practice. The extra cost might reduce the number of families HelpCureHD can help.

 

A cautionary tale from Brazil

 

Previously, I noted my long study of the disturbing history of abortion in Brazil, where it is illegal except in cases of rape and incest, danger to the life of the mother, and anencephaly, a fatal condition in which a fetus lacks a complete brain.

 

Each year, hundreds of thousands of women are hospitalized in Brazil because of complications of illegal abortions, and, overall, thousands have died. This tragedy provides a stark warning for the U.S. as it attempts to adjust to the Supreme Court decision.

 

I wholeheartedly agree with the emphasis on the medical – as opposed to religious ­– nature of the abortion question. I also believe in a woman and her family’s right to choose. In Brazil, I carefully studied – and came to identify with many of the ideas of – the local version of Catholics for a Free Choice.

 

The Supreme Court does not consider letters from the general public in its decisions. In April, I had begun exploring how to contribute to an amicus brief, which can only be filed by individuals or organizations registered with the court. I hoped to send a copy of an article I had published in 1995 in The Christian Century on abortion in Brazil as well as copies my blog articles on HD, abortion, and bioethics.

 

The stunning May 2 leak of the court’s draft majority decision made any potential input a moot point. The final version largely tracked the draft.

 

Respecting individual decisions

 

In the late 1990s, during a conversation about abortion with one group of poor women in a Rio de Janeiro slum, they told me: “cada caso é um caso,” that is, each woman’s situation is different.

 

After my 2011 articles on HD and abortion in the U.S., I came to that same conclusion after reflecting on the contrasting predicaments of the couple who aborted their gene-positive child and the 20-year-old JHD-affected woman who decided to have her untested, at-risk baby.

 

In the immediate aftermath of the news of the abortion decision, I was struck by the comments of Phil Metzger, the lead pastor of Calvary San Diego, a local Christian church

 

“My reaction is mixed, which you might not expect to hear from a pastor of a church,” Metzger said in a radio interview. While the decision was a victory for abortion opponents, it was also a moment to remember those struggling with the reversal of Roe v. Wade, he observed.

 

“Every place, I don’t care what institution it is, statistically, somebody in that group had an abortion,” Metzger continued. “So we have to ask ourselves, ‘Are they my enemy?’ They're not. And whatever reason brought them to making these hard choices, God loves them.”

 

Metzger’s words echo the middle ground sought by some in the abortion debate but drowned out by the fierce political and legal battles.

 

Sadly, the “hard choices” just got immeasurably harder for many women, especially those disadvantaged by poverty and, now, distance from the states where abortion will remain legal for at least the time being.

Surfing through life with the spirit of aloha

To persevere against neurological diseases such as Huntington’s and the aging we all face, I have learned that it is essential to develop meaning and purpose and perform mental exercise.

 

In May 1997, just seventeen months after learning that my mother had the devastating symptoms of Huntington’s, I confided for the first time in a medical professional who was outside my local support group. Explaining my family’s predicament, I revealed to a physician in Brazil, my second home, that I had a 50-50 chance of having inherited the HD mutation.

 

Thomaz Gollop, M.D., an OB-GYN, knew about the harm caused by genetic disorders such as HD and the enormous potential for psychological trauma involved when a family learned it was at risk: in Brazil he helped pioneer genetic counseling and testing, particularly for families who wanted to conceive.

 

I had gone to interview Dr. Gollop at his São Paulo clinic about abortion, a topic I was researching. Though Brazil, a fervently Catholic country, had outlawed abortion, millions of women found ways to terminate their pregnancies, often in precarious circumstances.

 

The disturbing history of this underground practice provides a cautionary tale for the U.S. as our Supreme Court prepares in June to apparently renounce five decades of protecting legal abortion. An affiliate of the American Society of Human Genetics and member of the American Association for the Advancement of Science, Dr. Gollop has been a leading advocate in Brazil for women’s health and legalization of abortion, emphasizing the medical – as opposed to religious ­– nature of the procedure.

 

I had not yet tested for HD. Because of my risk, my Brazilian wife Regina and I had postponed having children. I saw Dr. Gollop as a shoulder to lean on. I poured out my heart about my mother’s struggles and my fear of becoming like her.

 

Dr. Gollop told me: just keep doing what you like to do until the disease hits.

 

In my journey of risk – I tested positive for the mutation in 1999, followed by our daughter Bianca’s negative test in 2000 – I have frequently reflected on Dr. Gollop’s advice by imagining the simultaneous challenge and beauty encountered by a surfer riding a wave.

 

“Just keep surfing through life!” I tell myself.

 

Celebrating our 30th anniversary in Hawaii

 

During this, Huntington’s Disease Awareness Month, we must recognize the enormous caregiving and financial burdens imposed by HD. As a result, affected families must often relinquish their dreams. Regina and I did not have more children. We gave up buying a vacation condo in Brazil. I turned down an offer of a better job at a research university in another state so that, if I were unable to work, we could rely on Regina’s secure salary and pension from her job as a public school teacher.

 

My risk of becoming disabled means we have focused on saving, to bolster my long-term care insurance policy. So we usually take modest vacations.

 

This year, though, we splurged a bit. To celebrate our 30th wedding anniversary – which I had never expected to reach with the HD-free health I have enjoyed – we traveled to Hawaii for the first time. In late March we visited the islands of Kona (the Big Island) and Oahu.

 

We found Hawaii wondrous with its primordial, balmy setting: we saw molten lava flow in the crater of a volcano and heard a resounding chorus of birds sing at sunset. Along with newlyweds and other couples marking anniversaries, we were called to the stage at a luau to slow dance to a Hawaiian love song in celebration of “ohana,” the Hawaiian word for family.

 

Keeping alive the joy

 

I was introduced to the story of the father of modern surfing, Duke Kahanamoku (1890-1968), a native of the Waikiki neighborhood of Honolulu. A dark-skinned man competing in a world dominated by white athletes and sports officials, Kahanamoku impressed the world by winning gold and silver medals in swimming at the 1912, 1920, and 1924 Olympics.

 

Also active in rowing and water polo, Kahanamoku was one of the greatest athletes of his era. Always around beaches and pools, throughout his life he also saved many people from drowning.

 

I first read about Kahanamoku in a guidebook praising the popular Honolulu restaurant that he owned, Duke’s Waikiki. Powerful local interests had always capitalized on Kahanamoku’s fame to promote Hawaii as a tourist mecca but frequently abandoned him to struggle for economic stability on his own. He opened Duke’s late in life as a way to supplement his income

 

Regina and I visited Duke’s. It has Kahanamoku memorabilia, including one of his large wooden surfboards. Outside the restaurant Regina took a picture of me in front of a giant wall photo of Kahanamoku poised to take a dive.

 

 

Gene Veritas, aka Kenneth P. Serbin, standing in front of photo of Duke Kahanamoku in Honolulu (photo by Regina Serbin)

 

I was intrigued by Kahanamoku. Returning home to San Diego, I wanted to keep alive the joy I had felt in Hawaii. Exploring Hawaiian culture and history, I thought, might build for me new dimensions of meaning and purpose.

 

Surfing king Duke Kahanamoku and aloha

 

I delved into journalist David Davis’ Waterman: The Life and Times of Duke Kahanamoku, the first comprehensive biography of Kahanamoku (and the source of my observations here). By coincidence, the moving documentary Waterman, based on Davis’ book, premiered in theaters in April. I saw it on opening day.

 

In Hawaii Regina and I were frequently greeted with “aloha,” and people used “mahalo” to say “thank you.”

 

As an official greeter of visiting dignitaries (including President John F. Kennedy) and global ambassador for Hawaiian culture, Kahanamoku spent his life spreading the spirit of aloha.

 

Davis writes that Kahanamoku “suffused” visitors “with aloha because he believed that promoting Hawaii was beneficial for fellow Hawaiians.”

 

 

Regina Serbin at Chief's Luau with flowers presented in celebration of our 30th wedding anniversary (photo by Gene Veritas)

 

Kahanamoku printed his personal philosophy on his business card:

 

In Hawaii we greet friends, loved ones or strangers with ALOHA, which means with love. ALOHA is the key word to the universal spirit of real hospitality, which made Hawaii renowned as the world’s center of understanding and fellowship. Try meeting or leaving people with aloha. You’ll be surprised by their reaction. I believe it, and it is my creed.

 

(I have also frequently encountered sincere hospitality in my years of traveling and residing in Brazil and other Latin American countries.)

 

Although highly competitive in athletic contests, Kahanamoku’s embodiment of aloha gained him a reputation as a humble victor and cooperative teammate.

 

He refused to respond to the many racist epithets he endured. He suppressed his feelings when personally attacked or taken advantage of by others so much that he developed ulcers.

 

Nevertheless, with his athletic prowess and aloha, Kahanamoku entered areas of society normally reserved for whites.

 

As Davis observes, “Many years before nonwhite athletes like Joe Louis, Jesse Owens, and Jackie Robinson fought racism with courageous performances, Kahanamoku was a groundbreaking figure who was able to overcome – some would say transcend ­– racism.”

 

The wisdom of a waterman and his people

 

For Native Hawaiians, Kahanamoku’s plight symbolized the unwanted but steamroller-like annexation of the independent nation by the U.S. (in 1893); the adulteration of the environment by settlers from the mainland; the imposition of mainland culture and language on the locals; and, ultimately, the commercialization of society in favor of tourism, plantation agriculture, and the establishment of Hawaii as a major military installation.

 

In the words of another fine documentary, Hawaii is a “stolen paradise.”

 

Not surprisingly, Kahanamoku’s extended family retained no ownership in Duke’s Waikiki, which expanded to include restaurants on two other Hawaiian islands and also in three California coastal cities.

 

Despite this history, Hawaii fortunately has maintained much of its connection to nature and cultural traditions. With aloha and their intimate ties to the land and water, Kahanamoku and his fellow Native Hawaiians (along with natives elsewhere) offer a connection to premodern humanity and the importance of solidarity.

 

That spirit resonates with the fight for human well-being fundamental to the Huntington’s cause. As I tweeted in March, “Fortitude, collaboration of #HuntingtonsDisease movement embody opposite of aggression of war in @Ukraine: caregiving, alleviation of suffering, and harnessing of science for cures. #IStandWithUkraine.”

 

A “waterman,” Kahanamoku felt most at home in the sea, the source of life and the substance inhabiting our inner parts.

 

In a time of global warming, political strife, and warfare, the world has much to learn from the wisdom of aloha and Hawaiians’ immersion in nature.

 

 

Kenneth and Regina Serbin with Waikiki Beach and Diamond Head volcanic cone in the background (family photo)

 

Negotiating the waves of life

 

Modern surfing emerged from Hawaii. The greatest surfer of his time and global popularizer of the activity, Kahanamoku did not see it as a sport. It was about his love for, and relationship with, the sea. And about pure fun.

 

“The best surfer out there is the one having the most fun,” he said. After World War II, with the worldwide explosion in surf culture, competitions, and surfboard technologies, Kahanamoku marveled at ­– and was deeply proud of ­– how it took hold. He did want to see it included in the Olympics, which finally occurred in the 2020 games.

 

I tried surfing once in my 20s but did not pursue it. At 62 and still healthy, and with the example of Kahanamoku, I have thought of perhaps trying again, if I can find a patient instructor!

 

More importantly, Dr. Gollop’s advice rings true: to stave off Huntington’s onset, I need to keep doing what I like ­– including exploring Hawaiian culture and history.

 

The thought of Kahanamoku flawlessly negotiating the waves on his board also reminds me of the need ­– with aloha ­– to find in life “the right balance between striving and chilling.”

 

This week I am balancing my disappointment over a professional roadblock with the joyous celebration of Bianca’s graduation from the University of Pennsylvania.

 

I hope that those of us in the Huntington’s community and beyond can all learn to surf through life like Duke Kahanamoku ­– and always with aloha.

 

Regina (left), Bianca, and Kenneth Serbin during graduation weekend at the University of Pennsylvania in Philadelphia (family photo)

CHDI keynoter Charlotte Raven reflects on her fight against Huntington’s disease and the dashed hopes of a clinical trial

 

Like many affected by Huntington’s disease, renowned British journalist Charlotte Raven longed for the chance to participate in a clinical trial of a potential treatment for the incurable disorder.

 

Charlotte was diagnosed with Huntington’s in 2005. She inherited the genetic mutation from her father, who, after a long battle, died from HD in 2016.

 

In 2019 Charlotte had her wish fulfilled in London. As part of its HD clinical trial program to evaluate the efficacy of tominersen – the historic first attempt to attack the disease at its genetic roots – the pharmaceutical giant Roche was recruiting volunteers for GEN-PEAK, a small, Phase 1 study run in tandem with the larger, main, Phase 3 study.

 

Charlotte became “patient 1,” the first individual in GEN-PEAK to receive tominersen. If successful, the main trial would result in all participants in the program, including GEN-PEAK volunteers, receiving the treatment.

 

In her keynote speech at the recent 17th Annual HD Therapeutics Conference, Charlotte recalled the immense hope she felt about tominersen, shared by HD families around the globe: “Ever since I’d been picked to be on the trial, I’d woken up every morning thinking about the drug. It was like being in love. It was what I needed, wanted, looked forward to.”

 

A heartrending presentation

 

Those hopes were dashed on March 22, 2021, with Roche’s announcement that it was halting dosing of tominersen because of unfavorable efficacy data.

 

“Now that pinprick of light had been blacked out,” Charlotte told the 300 researchers, biopharma executives, and advocates gathered at the conference, held in Palm Springs, CA, and sponsored by CHDI Foundation, the nonprofit virtual biotech firm dedicated to developing HD therapies. “The world ended again; it felt exactly the same as the moment of my original diagnosis.”

 

Struggling with HD symptoms and assisted by her twelve-year-old son John, Charlotte bravely delivered a heartrending presentation, reading from a computer screen. Because Charlotte’s speech is slurred, the audience was provided access to an online script. She received a standing ovation.

 

Despite the bad news of 2021, drug hunters expressed renewed optimism about potential therapies. As reported in my previous article, the ensuing three days of scientific talks focused on multiple approaches. Indeed, Roche said it would test tominersen again in an improved clinical trial.

 

Assisted by son John, Charlotte delivers her keynote address (photo by Gene Veritas, aka Kenneth P. Serbin).

 

‘Feeling your personality crumble’

 

Charlotte’s keynote traced her career as an ambitious and controversial journalist and social commentator, her family’s fight against HD, and her efforts to cope with the symptoms and resulting limitations on her work and life.

 

The speech echoed Charlotte’s book Patient 1: Forgetting and Finding Myself, published last November. CHDI gave each conference attendee a copy.

 

In Patient 1, Charlotte provides a detailed, hauntingly beautiful portrait of the challenges posed by HD to both her and her extended family. Writing with help from her brother Daniel, as yet untested for the mutation, Charlotte intimately describes the toll HD has taken on her, robbing her of her memories and producing crippling anxiety.

 

“I wanted this book to be an accurate record of what it is like to exist with HD and to feel your brain and personality crumble,” Charlotte writes.

 

It also includes the first published account of the Roche program from a patient perspective.

 

‘A new leaf of hope’

 

During her CHDI keynote, to rest, Charlotte took two short breaks.

 

In the first interlude, with Charlotte looking on, her daughter Anna, 17, took the stage to speak of the special bond she has developed with her mother because of HD.

 

“Growing up under the shadow of Huntington’s has meant I’m often not the only priority, and sacrifices need to be made to make sure that my mom is properly looked after,” said Anna, who helps care for her mother.

 

Untested, both Anna and John have a 50-50 chance of inheriting the HD mutation. HD genetic testing protocols recommend against testing before age 18.

 

“Seeing and hearing about all these people working and researching to find treatments amazes me every day and makes everything seem a little less bleak,” Anna said. “The future for me, my brother, and my mom is unknown, but we have a new leaf of hope, and for that I would like to say thank you from the bottom of my heart.”

 

In the second interlude, Charlotte’s neurologist and clinical trial physician, Ed Wild, M.D., Ph.D., described her intellectual mettle. Dr. Wild wrote the Afterword to Patient 1. At the conference, he also recalled how “injecting 120 milligrams of tominersen into Charlotte’s spine in 2019” was one of his “proudest moments” in his career of helping HD patients.

 

Watch the entire keynote presentation in the video below, which includes the option of closed captioning.

 

 

The best team for defeating HD

 

Charlotte finished the speech with a tribute to researchers and a reflection on how confronting HD has “humbled me, and helped me connect more with the people around me, which is a new skill that I’ve been working on with commitment and persistence.”

 

“GEN-PEAK may have turned out to be a blind alley, but it was still a step on the journey towards a cure, and I still feel proud to have been part of it,” she said. “I’ve lived a fairly selfish life in lots of ways, so it seems oddly fitting that this last thing I did to save myself, might end up saving others instead.”

 

Charlotte noted an irony: she could write Patient 1, with its portrayal of HD's impact, only because the disease had mentally “compromised” her.

 

“I feel like I’ve finally been able to portray my family and friends as they really are instead of as I’d like them to be,” she added. “They are coming to life.”

 

She concluded: “Anna and I cannot get over how HD is such a rare disease, yet somehow attracts so many of the world’s brightest and best scientists. In my complicated journey with empathy, this is the most striking gift I can imagine.”

After a difficult year for the Huntington’s disease cause, CHDI chief scientist feels ‘reinvigorated’ and ‘optimistic’ about quest for therapies

 

Having faced negative results in two key clinical trials a year ago while battling the coronavirus pandemic, the Huntington’s disease community has renewed the quest for therapies (treatments).

 

A vital sign of this: despite initial fears about the omicron variant of COVID-19, the 17th Annual HD Therapeutics Conference took place ­from February 28-March 3 at the Parker Palm Springs hotel in Palm Springs, CA. The 305 fully vaccinated attendees gathered under a massive tent, which allowed social distancing and provided good ventilation.

 

Shortly after the March 2020 conference, much of the world went on lockdown to avoid the ravages of the virus, pushing the 2021 conference online.

 

“I don't think it's hyperbole to say that coming here for this conference in person feels like a rebirth,” said Robert Pacifici, Ph.D., in a half-hour interview with me on March 4. “It's been a hard couple of years for everybody, but for the Huntington's disease community in particular.”

 

Dr. Pacifici is the chief scientific officer of the conference sponsor, CHDI Foundation, the nonprofit virtual biotech entity geared solely towards finding HD therapies. CHDI is the largest private funder of HD research.

 

In March 2021, the community “learned that two of the really well thought-out and very rational clinical trials for Huntington's disease had been halted and it dashed a lot of people's hopes,” recalled Dr. Pacifici, referring to GENERATION HD1, the largest clinical trial in HD history, run by Roche, and two smaller trials with a similar drug run by Wave Life Sciences.

 

Those results “must have been devastating” for people awaiting an “efficacious treatment,” Dr. Pacifici continued. “But we do what the Huntington's community always does: we persevere, we lift ourselves up by our bootstraps, and we go forward.”

 

Witnessing a “bunch of reasons” for hope about therapies at the conference, Dr. Pacifici declared, “I'm reinvigorated and very optimistic.”

 

For an overview of the conference and my interview with Dr. Pacifici, watch the video below.

 

 

Above, HD Therapeutics Conference attendees view scientific posters presenting new research, and, below, watch one of the many presentations at the four-day event (photos by Gene Veritas, aka Kenneth P. Serbin).

 

 

Learning from last year’s setbacks

 

At the Therapeutics Conference, Roche elaborated on new data from GENERATION HD1 and its plans to develop an improved clinical trial. Wave provided an update on its new early-stage trial, SELECT-HD.

 

Both firms use gene silencing drugs to attempt to reduce the amount of the toxic huntingtin protein in the brain (called huntingtin lowering). Both seek to build on the lessons learned from the 2021 setbacks.  (Click here to read about Roche’s recent announcement and here about Wave’s new trial.)

 

“I'm heartened that there's still a lot of enthusiasm for the huntingtin-lowering approach,” Dr. Pacifici observed. “There's actually a very impressive portfolio of other companies, therapeutic modalities, and approaches to huntingtin-lowering.”

 

Other plans to attack the mutant protein

 

PTC Therapeutics and Novartis Pharmaceuticals presented updates on their respective ongoing clinical trials using different huntingtin-lowering approaches. Whereas Roche and Wave drugs were administered via an uncomfortable spinal tap done at a clinic, PTC and Novartis use so-called small molecules: pills.

 

Besides the obvious convenience, such small-molecule drugs offer other key advantages, Dr. Pacifici explained.

 

“We know that mutant huntingtin is expressed everywhere [in the body] and so it’s good to know that you can lower it everywhere with a small molecule,” he said, noting that dosages can then be calibrated to achieve different lowering effects.

 

A higher dose creates more lowering, while a lower dose lessens it, Dr. Pacifici explained.

 

“From a safety perspective, if we ever found a long-term problem with huntingtin lowering, you can stop taking the compound and let the huntingtin come back so that then you can decide,” he continued, referring to a practice called picket-fence dosing, in which patients stop and restart dosing as needed.

 

Triplet gears up to test its approach

 

With no guarantee that reducing the toxic protein will result in an effective treatment, the Huntington’s field has purposefully diversified.

 

A key example is the work of Triplet Therapeutics. Triplet focuses on somatic expansion (also known as somatic instability), the tendency in HD of the already expanded (and therefore mutant) huntingtin gene to continue growing in length with age. The greater the expansion, the earlier the impact of the mutation on brain cells. This process is governed by recently discovered modifier genes that slow or hasten disease onset. (Click here and here to read more.)

 

“That's what actually causes the cells to malfunction, to die, and eventually leads to the underlying physiology of Huntington's,” Dr. Pacifici said. “So, not surprisingly, that gives us another therapeutic handle. Can we slow down that somatic instability?”

 

At the conference, two Triplet scientists presented a preliminary analysis of data from SHIELD-HD, a research study of 70 presymptomatic and early-disease-stage carriers of the HD mutation. SHIELD-HD is furnishing data for a clinical trial of Triplet's drug candidate, TTX-3360, aimed at blocking somatic expansion and, therefore, potentially delaying or avoiding HD onset.

 

Triplet Therapeutics scientists Irina Antonijevic, M.D., Ph.D., the chief medical officer (right), and Peter Bialek, Ph.D., senior director of translational science, after their presentation at the HD Therapeutics Conference (photo by Gene Veritas)

 

Founded in 2018, Triplet has used the science of somatic expansion and HD modifier genes to move with “record-breaking speed” towards a clinical trial, Dr. Pacifici said.

 

In a brief interview after the Triplet presentation, Irina Antonijevic, M.D., Ph.D., the company’s chief medical officer, confirmed that it will file a Clinical Trial Application this summer for permission to start a Phase 1 dose escalation clinical trial of TTX-3360, mainly to test safety and tolerability. Regulatory agencies can take a few months to review the application, after which the firm could start recruiting people with HD.

 

“We’re very excited,” Dr. Pacifici said. “The whole area of somatic instability is a great complement to huntingtin lowering. It's possible that eventually, if God forbid, huntingtin lowering turns out not to be viable, we've got a great backup plan. But even if it is, these things could actually synergize with each other. I could imagine people in the future being treated with a combination of therapies that address both of these things – lowering the huntingtin protein, but also preventing additional somatic instability.”

 

A future article will explore the SHIELD-HD presentation and Triplet’s clinical trial plans.

 

The value of family participation

 

Most of the conference presentations focused on human data, as opposed to research in animals. Dr. Pacifici pointed out that many advances in HD research result from the participation of thousands of gene carriers in studies and clinical trials.

 

“I appreciate that families are willing to give their time, their blood, their urine, and the travel, the poking, the prodding they're going through,” Dr. Pacifici said. “I want to express my heartfelt gratitude. This year, more than ever, I guess I'm happy to say I told you so, meaning that I always encourage people to participate and we're now seeing the fruits of that participation. We now have the evidence that those samples are being used judiciously and are providing unparalleled value.”

 

Dr. Pacifici also pointed to the steadfast commitment of both scientists and families to HD research during the pandemic, which “required people taking risk and going into the clinics and the labs.”

 

“Hang in there, be resilient, participate when you can,” Dr. Pacifici concluded, because a “really talented, committed global group of passionate drug discovery professionals would love nothing more than to deliver what you need so desperately, which are effective treatments for Huntington's disease.”

 

For my coverage of the start of the conference, click here.

 

For additional coverage, visit HDBuzz.