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.”

Upbeat Huntington’s disease film, featuring undaunted family, aims for 10 million viewers

The Longest Journey – a new feature-length documentary film about Huntington’s disease – portrays the undaunted Shaffer family in an epic battle.

In June 2015, for the fourth time in ten years, Renato Shaffer of San Diego led a team of four men in the Race Across America (RAAM), a non-stop bicycle race from the pier in Oceanside, CA, to the boardwalk in Annapolis, MD. (In 2008, Renato also led an HD team in the Race Across the West.)

Their goal: to raise awareness about HD and support the effort to save Renato’s 48-year-old wife Sharon and 30,000 other Americans from the devastating, fatal neurological disorder and prevent it from striking the Shaffers’ two untested, at-risk daughters, Alexa, 25, and Taylor, 20.

Beautifully shot and directed by rising filmmaker Nathan Apffel and with inspirational sound design by Brandon Puda, The Longest Journey captures the heights and depths of the 3,200-mile race, which riders must complete in eight days or face disqualification.

“My motivation is, yeah, I’m going to suffer for seven days, but somebody with HD – they’re suffering until the end,” 50-year-old Renato says in the film. “After seven days, I get off my bike, I’m feeling good, but with HD, each day makes it worse, gets worse, gets worse, until the end, you’re just a shell of the person you used to be.”

However, as in the RAAM, the Shaffers haven’t given up the fight against HD. Along with Nathan, they want the film to help bring a cure.

In contrast with most presentations of HD I’ve witnessed in the two decades since my mother’s diagnosis for the disorder, this often emotionally wrenching film left me, an HD gene carrier, feeling upbeat.

Seeing Sharon strive to overcome HD with the help of workouts and the RAAM team compete in an event that would challenge even the best-trained Olympic athletes, I felt newly motivated to exercise, a scientifically proven way to promote brain health.

I was also inspired to renew my commitment to advocacy.

Huntington’s is so cruel. It was refreshing to see someone offer a more hopeful interpretation.

Nathan, in his role as narrator, indicates this intention at the outset: “And you might be sitting there thinking, ‘Great, another movie about getting older, the age clock spinning faster, and the happiest times were when you were a child and hadn’t faced the music yet.’ Well, I’m hoping for all our sakes this movie’s a bit bigger than that.”

You can watch the film trailer by clicking here.

Marketing the film

Nathan and producer LeeJ Razalan, a RAAM supporter and Shaffer family friend, held a private screening of the film for friends and family members in San Diego on May 19. About 200 people attended the screening, which also served as a fundraiser.

In an interview after the screening, Nathan said he expects to release the film in the next three to six months. His previous films and programs have appeared on Netflix, Bravo, Hulu, and ESPN, and he hopes to place this film with an online streaming site, aiming for ten million viewers.

Nathan, LeeJ, and the Shaffers want to educate as many people as possible about HD, and to raise funds for research.

The professional quality of The Longest Journey, its potentially wide viewership, and its positive outlook could make it a successful awareness-building vehicle.

Renato Shaffer (left), Sharon Shaffer, LeeJ Razalan, and Nathan Apffel (photo by Gene Veritas, aka Kenneth P. Serbin)

Fighting until she can’t fight

We learn in the 75-minute documentary that Renato married his high school sweetheart despite knowing her father had HD and that she might have inherited the genetic defect.

“She’s fighting a good fight,” he says. “At this stage, her father was already pretty far gone. She’s 48 now, and at least she can still speak, she can still communicate. She still has a little bit of freedom to do what she needs to do, as opposed to her father, who pretty much gave up.

“When he found out that he had it, he tried to kill himself a couple times. Not Sharon. She’s fighting until she can’t fight anymore.”

“It scares me that my whole family’s out there,” Sharon, her speech slurred by HD, says about the dangers of the long race, which originated in 1982. “There’s been deaths. There’s been accidents, so many accidents.”

Some teams “never come back the same,” she adds. Already by Colorado, 24 teams had to quit the 2015 race, unusually grueling because of extremely hot weather in the West, as shown in the film.

In past races, Sharon helped as a support team member on the road. In 2015 HD kept her home. She flew to Maryland with other family members on the last day.

Valiant people

Everybody in The Longest Journey is on a personal mission against HD, including Nathan, whose HD-affected brother-in-law has two young, at-risk children.

Nathan skillfully interweaves scenes from the Shaffer team’s spectacular athletic performance with interviews with Sharon, Renato, his teammates, and the Shaffer daughters and their boyfriends.

Also interviewed is Sharon’s physician, Jody Corey-Bloom, M.D., Ph.D., the director of the Huntington’s Disease Society of America (HDSA) Center for Excellence for Family Services and Research at the University of California, San Diego. Dr. Corey-Bloom explains the causes and symptoms of Huntington’s, providing a counterpoint to scenes in which we see Sharon speaking or fighting to overcome her condition.

As disabling symptoms gradually appear, HD patients “absorb” many “blows,” Dr. Corey-Bloom says.

“These are young people struck down at very productive points in their lives,” she adds. “There’s a valiant nature to people.[…] People are just so amazing in the way they handle it and deal with it and just try to keep going on.”

The desire to survive

The Longest Journey bravely ponders HD’s endpoint: death.

“I think the hard thing for people to […] talk about is that it’s fatal,” Dr. Corey-Bloom comments.

However, The Longest Journey doesn’t dwell on death. On the contrary, it focuses on the RAAM, the Shaffers’ efforts to defeat HD, and their large network of supporters.

Sharon is living with her HD, and her family along with her, to the greatest extent possible.

Sharon and her family do CrossFit exercises in the Shaffer garage, converted into a gym.

Nathan projects Sharon’s desire to survive and her family’s hopes for a cure by focusing on their expressions during interviews and moments of the RAAM.

“I still feel: what an amazing lady,” says Dr. Corey-Bloom, recalling that Sharon before HD onset was articulate and employed by a drug company. “She is tough. I am sure there must be days when she sort of thinks, ‘Why am I even bothering?’ She’s out there. She campaigns for things. Renato makes that grow.

“These are two people who, at least in San Diego, everyone looks up to.”

Sharon and Renato (photo by Gene Veritas)

Good-natured and humorous

Nathan balances the many difficult challenges of RAAM and the struggle against HD with moments of humor and optimism.

“It’s only the end of the first day, and I didn’t know a body could sweat as much as I’ve sweat in the last few hours,” he observes. “Our vehicle’s already starting to smell like day-old beef stroganoff.”

Alexa good-naturedly refers to sister Taylor as a “neat freak” who bought “ten Glade air fresheners” for the two vans the riders eat and sleep in when off the road.

“Mother nature beat us up a little bit,” observes teammate Jason Tate, 45, about the winds and heat.

These and other moments made the audience laugh.

Wisdom on HD

Through the interviews with the Shaffers and their friends, The Longest Journey offers much wisdom for the HD community.

The documentary exemplifies how families can unite – not split – when faced with the myriad challenges of HD. It also demonstrates how people like LeeJ, a friend with no blood connection to HD, provide crucial support for the cause.

As HD advocacy, The Longest Journey can potentially draw out of the “HD closet” those individuals and families needed as volunteers at events and in research studies and clinical trials.

Projecting optimism

Like The Lion’s Mouth Opens, Removing the Mask, and other films about HD, The Longest Journey offers a unique perspective.

After the screening, some attendees had tears in their eyes. However, the audience also applauded enthusiastically.

In talking with the audience, Nathan and LeeJ projected optimism.

I believe that optimism is indeed the film’s most important quality. I listened with great interest to Nathan and LeeJ’s recollections and their plans to attract viewers.

They recalled how the project was born after Nathan met Sharon, who was wearing a RAAM t-shirt, met at the 2015 HDSA-San Diego Hope Walk.

“Everything was serendipitous up to today,” said Nathan.

He explained that a film like this normally costs $300,000 to $500,000.

“The coolest part is that we made this one for 20,000 bucks,” he said. “Don’t get me wrong. There’s a lot of blood and sweat equity put into this.”

Noting that he shot the film in 4K (ultra high-definition) resolution/high dynamic range, the next generation TV technology, he added: “We’ve future-proofed this film for the next ten years.”

As of that evening, Nathan and LeeJ still needed $8,000 to reach their $20,000 basic budget. In an e-mail the next day, LeeJ announced that donations from the screening amounted to $9,000.

LeeJ with racing bike to be raffled to support the HD cause (photo by Gene Veritas)

A raw and authentic story

They will now focus on marketing the film, including film festival submissions.

“This is my strongest [film], hands down,” Nathan told the audience. “I think it has the heart and the quality. I want to open or close Sundance or a really, really big festival.”

LeeJ calls The Longest Journey a “raw and authentic instrument to share the story of HD.” As a slogan to accompany the film, they’re considering “better together,” a reflection of its emphasis on family and community unity.

As Sharon states at the end of the film, in a message relevant for all HD families: “My advice would be to just continue to love yourself and your family.”

To donate to the Shaffers’ efforts to combat HD, click here.

Renato (left) and Nathan (photo by Gene Veritas)

Engaging a ‘scared population’ of Huntington’s disease families by respecting their journeys

The number of clinical trials for Huntington’s disease treatments has increased exponentially, pushing up the demand for volunteers. Now advocates ask a pressing question: how to inspire more affected families and individuals to participate?

I have addressed this theme with increased frequency in recent years, as in my last two articles (click here and here to read more). As a carrier of the devastating HD mutation who saw his mother succumb to the disease, I feel in my gut the urgency to involve other members of the community.

“If no patients or gene-positive people show up for trial participation there will be no novel treatments, ever!” Daniel P. van Kammen, M.D., Ph.D., wrote in an e-mail in response to my articles.

For several years, I have maintained a dialogue on this topic with Dr. van Kammen, from 2007-2011 the chief medical officer for CHDI Foundation, Inc., the nonprofit virtual biotech focused exclusively on developing HD treatments. A professor emeritus at the University of Pittsburgh, Dr. van Kammen currently serves as an independent consultant for central nervous system (CNS) clinical trial development.

“The notion that if you build it they will show up, just does not work!” Dr. van Kammen continued. “In general only 5% of people diagnostically eligible for drug development study participation, do so. This is fine for a large population with Alzheimer’s. Not for the HD community either at risk or diagnosed. So people have to come forward.”

As he indicated, there’s a relatively small number of HD-affected individuals, estimated at 30,000 in the U.S. By contrast, as many as 5 million Americans over age 65 may have Alzheimer’s.

Beyond that, a good number of HD-affected individuals cannot participate in clinical trials because of so-called exclusion/inclusion criteria. (I’ll write about this issue more in a future article.) So that leaves an even smaller number of potential trial subjects.

The Enroll-HD program, the global platform, research project, and family registry aimed at facilitating clinical trials and the discovery of treatments, recently marked its 5,000th registrant but needs as many as 25,000 more volunteers.

People deciding at their own pace

Over my nearly two decades of advocacy – my mother was diagnosed in 1995 – I have learned that it’s important to respect the unique journey of each individual touched by HD. Without that respect, we cannot begin to engage what Dr. van Kammen described as a “scared population.”

From a pure research standpoint, the more at-risk people who test for the HD gene, the better. Despite the enormous psychological burden of knowing that I will develop HD, I don’t regret undergoing genetic testing.

I often wish that more individuals from the untested at-risk pool – the vast majority of those people don’t  get tested – would also test and/or participate in programs such as Enroll-HD, which doesn't require that people learn their genetic status.

But then I remember how I wanted to get tested immediately after learning of my mother’s diagnosis. I postponed the decision after receiving advice regarding the discriminatory consequences of testing, and, more than three years later, bit the genetic bullet because my wife and I wanted to know my status before starting a family. Six months later our daughter tested negative for HD in the womb.

What a journey!

When I meet people new to HD, I am aware that I can offer ample advice based on experience. However, I stick to the basics, allowing them to ask questions and share their stories and fears at their own pace. I remind myself that testing for HD is often an extremely trying process, with implications for the extended family. This personal decision requires time and reflection.

People new to HD are embarking on their own journeys based on their backgrounds and particular point in life.

The same respectful approach applies in encouraging people to attend a support group, visit the local HD clinic, participate in fundraising activities, and enrolling in studies and clinical trials.

The dynamics can be complex. In the face of HD, many families close ranks. However, many split, beset by fear, denial, and the stigma of HD.

Activists’ self-respect

I have received enormous respect from my fellow HD advocates.

We activists must always remember to respect our own journeys.

At 55, I have passed the age of my mother’s HD onset. Each day without symptoms is a gift.

To maintain self-respect, I must allay guilt about doing too little for the cause. I especially feel this way when missing a support group meeting or a local event of the Huntington’s Disease Society of America (HDSA).

Lately I have also faced advocacy fatigue. However, seeing other, often less fortunate families suffer from HD – like the young man holding his HD-stricken grandmother or the family with members stricken by both adult-onset HD and juvenile HD – leads me to gird myself again for the fight. On April 11, at an HDSA educational event at the William W. Backus Hospital in Norwich, CT, I will share my story and the hope offered by the upcoming gene-silencing clinical trial planned by Isis Pharmaceuticals, Inc., and Roche.

In re-engaging, I remind myself that my journey is unique, too, with my own particular moments and needs.

Enjoying the present, planning the future

Twenty years into the cause and ever closer to disease onset, I need to focus on my health, enjoying life, and my family.

With a sabbatical from teaching duties, I am also writing a long-gestating book on Brazilian politics that I had partially put aside because of my work as departmental chair the past five and a half years and my developing interest in the history of science, technology, and medicine.

As our daughter approaches college age and my wife and I initiate conversations about retirement plans, we are also focusing on shoring up the family finances. As all HD families know, losing a working family member to the disease not only severely reduces family income but also creates a caregiving burden very costly in both time and money.

Luckily neither of lost our jobs in the Great Recession, but like many Americans in the eroding middle class we have received little or no increase in income during the recovery.

At 55, I also face the normal challenges of aging. Over the past eight months I have struggled with a nagging elbow pain that has prevented me from swimming, my preferred exercise and excellent for cardiovascular and brain health. Luckily, with my doctor’s okay, I am back swimming, although the pain continues. Because of pain elsewhere in the body, I have spent many an hour at physical and occupational therapy sessions.

I want to remain as limber as possible to facilitate coping with HD symptoms (more on this in a future article).

I also continue to exercise my mind. As I wrote to an old friend regarding the recent tenth anniversary of this blog and its 200th article, “Writing for survival is my motto.”

Affirming the good in our lives

Like many others in the HD community, my journey has deepened my search for spiritual meaning.

I have added another book to my morning meditation, Gratitude Works!, a book about gratitude journaling by Robert A. Emmons.

Writing regularly about the positive experiences in our lives promotes a shift in awareness from “what we are lacking to the abundance that surrounds us,” Emmons writes.

“Gratitude leads us to affirm and acknowledge the good things in our lives,” he adds.

Our community has immense suffering, but is also has immense good.

I am grateful for remaining asymptomatic today, for the many people bravely struggling to come to terms with HD, and for the great respect the members of the HD community have for each other as we live our unique moments together.

I’ll be even more grateful when more people enroll in clinical trials. Yes, we may be a “scared population.” But we may also be a “sacred population,” one dedicated to a deeper purpose, helping to conquer this awful disease.