After another critical Huntington’s disease clinical trial proves negative, a time to embrace self-care and caregiving

 

A long-awaited clinical trial of a drug aimed at improving daily function  in the early stages of Huntington’s disease has produced negative results, Prilenia Therapeutics announced on April 25 at the American Academy of Neurology meeting in Boston.

 

According to Prilenia, the drug, pridopidine, failed to show improvement for trial participants on its primary and secondary measurements of symptoms (endpoints).

 

"Unfortunately, the failure of the PROOF-HD trial to meet its primary endpoint in preliminary analyses is a huge disappointment for the HD community,” Jody Corey-Bloom, M.D., Ph.D., the director of the Huntington’s Disease Society America (HDSA) Center of Excellence in San Diego, wrote me in an e-mail on April 25. “There was, however, some suggestion of benefit on other clinical measures, particularly a computerized assessment of motor function [a person’s movements], and I suspect we will see additional detailed analyses in the coming months.”

 

“We won’t sugar-coat this: the trial results were unfortunately negative,” the HD science site HDBuzz concluded. “The drug did not slow progression of HD as measured by the TFC [Total Functional Capacity]. Failing to meet its primary endpoint means that pridopidine will not get licensed by the FDA and other regulatory agencies.”

 

“The data obtained as part of the study remain useful and will be analyzed further for new insights they can provide,” Martha Nance, M.D., the HDSA Center of Excellence director in Minneapolis, wrote me. “We will not stop looking for better answers.”

 

Seeking a disease-modifying therapy

 

As an HD gene carrier who will inevitably develop symptoms, I had hoped to take pridopidine – if prescribed by a doctor – to help prevent or slow disease onset and maintain my daily activities. At 63, I have reached far beyond my HD-stricken mother’s onset in her late 40s. She died at 68.

 

Pridopidine would have been the first drug to potentially affect the progression of HD. Also, unlike drugs in other key trials that require spinal injection or direct injection into the brain (requiring an operation), pridopidine is a pill.

 

The news about pridopidine is the latest in a series of disappointing clinical trial news over the past two years. Last October, the highly innovative Triplet Therapeutics, Inc., had to shut down because of investor nervousness about the HD field. In December, Novartis had to end a program of developing its own pill for HD, branaplam, because of serious side effects in volunteers in a clinical trial.

 

PROOF-HD was a definitive Phase 3 trial. There are no other Phase 3 HD trials in progress for disease-modifying therapies.

 

Researchers remain hopeful that they will ultimately develop effective therapies. In January, Roche announced the start of GENERATION HD2, a second, less ambitious clinical trial of its gene-silencing drug tominersen. Other trials are in progress. This week, scientists and drug hunters focused on the cutting-edge developments at the 18th Annual HD Therapeutics Conference in Dubrovnik, Croatia (click here to read more).

 

Prilenia CEO and founder Michael Hayden, M.D., Ph.D., reporting the negative results for improvement in Total Functional Capacity in PROOF-HD participants at the HD Therapeutics Conference, April 27, 2023 (photo from HDBuzz)

 

Stepping back from advocacy

 

With the rest of the HD community, I have been riding the “clinical trial roller coaster” of emotional ups and downs in the quest for therapies.

 

I am also acutely aware of the passage of time – and that I may never get to participate in a clinical trial. GENERATION HD2, for example, restricts participation to ages 25-50. In the 30 years since the discovery of the huntingtin gene, we still have not seen a therapy to slow, stop, or reverse the disease. This month marks 25 years of my work as an HDSA volunteer advocate.

 

Recently, due to unforeseen circumstances unrelated to HD, I have had to step back from my advocacy, including this blog. My current challenges come on top of the juggling act that has characterized my fight against HD since my mother’s diagnosis in 1995 and positive test for the mutation in 1999.

 

So I have struggled to maintain my sense of meaning and purpose – crucial in slowing cognitive decline in HD. 

 

I have thus felt the need to concentrate on self-care. I believe there is wisdom in recognizing the importance of self-care – especially for someone like me facing a challenge for which science has yet to find an answer.

 

As I have learned, my first obligation is to my own health – remaining symptom-free and therefore fully available for my family, friends, and others I love and care for.

 

In this blog I have aimed for transparency about my health. For my own and the community’s benefit, I have sought to report accurately and thoughtfully on the quest for therapies, the endeavor to provide better care, and the many ramifications of HD (click here to read more).

 

Prioritizing diet, sleep, and exercise

 

So, as an advocate striving to be the best version of himself, I want to embrace self-care.

 

Last August and September, though fully vaccinated and having masked except for meals, I fought off an infection of COVID-19 caught in Boston while attending HD2022: Milton Wexler Biennial Symposium, sponsored by the HD-focused Hereditary Disease Foundation. I have been deeply concerned about COVID-19 because of the many instances of long COVID, the disease’s neurological symptoms, and the devastating impact on people in their 60s and older.

 

The pandemic has highlighted the need for self-care and caregiving.

 

To continue HD-free, I must prioritize the triad of a healthy diet, adequate sleep, and regular, vigorous exercise. I tell myself about swimming: in terms of health, “this is the most important thing you can do today.”

 

Recently, after challenges replacing my retired psychotherapist of 24 years, I began working with a new therapist – a profound form of self-care.

 

Self-care for me also includes continued participation in Enroll-HD and other HD research studies.

 

 Gene Veritas (aka Kenneth P. Serbin) swimming in his backyard pool (family photo)

 

Addressing deficits in care and caregiving

 

With the negative results from PROOF-HD and other recent trials, I am reminded of the debate and tensions over “care versus cure” that I witnessed at the start of my HDSA advocacy in the late 1990s and early 2000s. We need both. I saw my mother’s desperate need for care as HD devastated her and fought with fellow advocates to support the search for a cure.

 

As I age, and with the continued lack of effective therapies, the likelihood that I will not take a disease-modifying drug increases – as does, therefore, the likelihood that I will need caregivers. For HD gene carriers like me, improvements in caregiving will become essential.

 

As one key study has shown, serious deficits HD in care and caregiving remain, and plans for addressing this issue remain aspirational.

 

Most HD funding goes to biomedical research. Greater resources for HDSA and other patient advocacy organizations could help address the care and caregiving shortfalls.

 

Being patient and gentle with human fragility

 

Upon entering this world, we are all subject to illness, both genetic and non-genetic. The fight against HD, COVID-19, and other illnesses highlights our human fragility.

 

We are all potential caregivers and recipients of care, at various times in our lives.

 

I have found heart in the words of Pope Francis during his historic May 2017 audience with the HD community at the Vatican, which I attended with my family: “Fragility is not an ill, and disease, which is an expression of fragility, cannot and must not make us forget that in the eyes of God we are priceless. Disease can also be an opportunity for encounter, for sharing, for solidarity.”

 

As I patiently and gently await the recharging of my mental and spiritual batteries, I am mindful of my own – and others’ – fragility and the new opportunities for solidarity in achieving research progress and improved caregiving.

My Huntington’s disease sister – and a hero who strives for the unthinkable

Sharon Shaffer is my Huntington’s disease sister – and my hero.

Afflicted with progressively worse HD symptoms the past 15 years, San Diego area resident Sharon decided to once again attempt the unthinkable for someone heading into the final years of the fatal, incurable disorder: she rowed the equivalent of an aquatic marathon (26.2 miles) on a gym machine in six and a half hours.

The May 10 event, with loved ones and supporters cheering her on, was called “Sharon's Marathon Row for Huntington's Disease Awareness Month.” 

Sharon’s feat was captured in a five-minute video titled Magic on Marathon Row, produced by filmmaker Nathan Apffel, who also directed the feature-length documentary The Longest Journey, about the Shaffer nuclear family’s epic battle against Huntington’s.

A scene from Magic on Marathon Row

“When disease takes your health and mobility and will take your life, you have a choice,” the video’s overlying text says. “Meet Sharon, a real-life super woman. As Sharon’s body gives out, her determination grows. As her world contracts, her commitment to raising awareness intensifies. As her body breaks down, one thing remains consistent: her determination to fight.”

Sharon’s husband Renato told me in an e-mail that, despite her advanced HD symptoms, she did the "marathon" through “sheer perseverance.”

“It is the only exercise she is able to do without assistance,” he added.

“Sharon, you truly are an inspiration to so many,” wrote E.J. Garner, the chair of the board of the Huntington’s Disease Society of America, in response to my Facebook posting of the video. “Thank you for being such a beautiful example of persistence to fight and bringing awareness to Huntington's disease.”

“She completed a feat only few in the entire world, even healthy and athletic, would not dare approach, let alone finish,” observed LeeJ Razalan, a friend and the owner of Stay Classy CrossFit, the San Diego gym where the event took place. “Sharon's statement in life and in disease will forever ring: we shall overcome and we will finish this together."

Watch Sharon in the video below.

Advancing symptoms

The “marathon” exhausted Sharon. “She could barely move when we got home and took a good three days for full recovery,” Renato explained.

With her family’s help, Sharon has remained one of the most physically active HD-afflicted individuals I have encountered. The highly demanding CrossFit workouts have been one of her favorite activities.

Renato believes that CrossFit delayed Sharon’s need for a wheelchair.

“I also believe the people she worked out with gave her motivation,” he added. “She always looked forward to working out.”

However, Renato also described CrossFit as a “barometer” of HD progression.

In recent years she has become physically weaker, and the involuntary movements caused by HD have increased.

“We have witnessed a rapid decline in the past twelve months,” Renato wrote. “She is no longer able to walk unassisted, and her speech is becoming more labored every day. We have full-time in-home care and are so fortunate they are doing a really great job taking care of her.”

Sharon still exercises, but “it gets more difficult every week,” Renato added.

Renato allowed Sharon to row in the “marathon,” he wrote, because as symptoms worsen, exercise will become impossible. That moment will be "heartbreaking."

An upbeat family

I met Sharon about two decades ago at the HDSA-San Diego support group. With others in the breakout group for presymptomatic gene carriers like us and also the untested at-risk, we shared our fears about the disease and its consequences for our children and extended families.

The Shaffers became one of the most active supporters of the cause. Between 2005 and 2015, with Sharon, family members, and others following in support vehicles, Renato and three other riders competed four times in the Race Across America, a non-stop coast-to-coast bicycle race. They always completed the race in fewer than the required eight days.

The Longest Journey documentary chronicles the 2015 race. “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,” I wrote in a review of a private screening of the film in 2016 (click here to read more). 

The closing words of Sharon’s rowing video ask viewers to learn more about Sharon’s story by watching The Longest Journey. (It’s on Amazon and free to Prime members.)

According to Renato, Amazon statistics reveal that the film has been viewed 200,000 times.

The essential goal: treatments

Sadly, I’ve witnessed how HD has overcome Sharon, transforming her from a healthy and vibrant woman into someone now dependent on a wheelchair and the assistance of others.

However, Sharon has demonstrated that, despite the ravages of the "devil of all diseases," the core of her personality has survived.

As we enter the final week of HD Awareness Month, Sharon’s gutsy fight reminds us all that we must not give up in the face of Huntington’s difficult challenges.

For me, Sharon’s devotion to exercise is a cue to spend more time swimming.

At the same time, exercise, although certainly important, has not stopped Sharon’s HD from progressing.

We need effective treatments – urgently.

In the HD movement, advocates create moments that capture the essence of the cause.

In defying seemingly insurmountable obstacles, the Shaffers remind us of the immense scientific, financial, political, and social challenges that the HD community faces in seeking to find the first effective treatment – and perhaps even a cure – for a neurological disorder.

Support from unaffected relatives makes big difference in fight against Huntington’s disease

May is Huntington’s Disease Awareness Month.

Building awareness in the fight to defeat HD means expanding knowledge of this deadly brain disorder beyond directly affected individuals and their families. Ultimately, an effective campaign must actively involve the unaffected, both relatives and friends.

George Essig epitomizes the dedication of the unaffected relative.

For families like mine – my mother died of HD in 2006, and I carry the genetic mutation – individuals like George bring hope alive.

“I remember as a child my uncle walking in a very clumsy manner and at one family event even spilling his entire plate of food on the living room floor,” George says in the May 15 edition of “Faces of HD,” a daily autobiographical advocacy mini-profile disseminated via e-mail and social media by the Huntington’s Disease Society of America (HDSA) during May. “People kind of looked away. My aunt cleaned things up amidst the awkwardness. My uncle got progressively worse and could not enunciate his words.

"I remember that the family thought his son, my cousin, as a young boy was mirroring his father's actions. We found out of course that he had child onset Huntington's disease. He died at age 19."

George Essig

Nobody in George’s extended Midwestern family wanted to talk about HD, he remembers.

“My parents would not talk about it,” he continues. “I learned my grandfather had it. My uncle tried to commit suicide in the basement of his home using gasoline from the lawnmower. My cousins' boyfriends at the time had to clean it up.”

In 1975, George moved to San Diego.

“Huntington’s was lost in my memory,” he says. “I am one of eight kids. It wasn't until my Dad was in his seventies that we figured he did not inherit the defective HD gene.”

About twelve years ago, George and a sister, Kathleen Martinek of North Carolina, started wondering what had happened to the branch of the family affected by HD. As they got back in touch, they learned of the terrible devastation wrought by the disease.

Eventually they would discover that HD had stricken not only his grandfather and uncle, but another uncle, an aunt, three cousins, and a number of second and third cousins.

The disease also caused collateral damage, devastating those who lived at risk but did not develop symptoms.

“I found out recently from (a cousin), now 69, who we had lost track of, that she experienced the deterioration of her entire family and her own mental health,” George says. “She doesn’t want to talk about Huntington’s disease. She and her husband adopted children.”

George assumes the cousin had preferred to adopt rather than run the risk of passing on the mutation to biological children. Each child of an HD-affected parent has a 50-50 chance of inheriting the mutation.

To learn more about HD and the effort to stop it, George contacted members of HDSA-San Diego. In 2006, he joined the chapter board of directors. (I served on the board from 1998-2010.)

“I would like to help raise money for a cure and educate people about Huntington’s – starting with my own family and friends,” George said in an article about him that I wrote for the HDSA-San Diego newsletter.

I noted that George and his wife Theresa lived in Poway, CA. The couple has three grown daughters, who work in medicine, law, and education. George's hobbies include growing avocados, and he enjoys swimming and bicycling.

For about a year, George quietly observed the other board members at work. At the time, he told me he was searching for an effective niche on the board.

George Essig studies documents at the May 2007 meeting of the HDSA-San Diego board of directors (photo by Gene Veritas).

George had an infectious smile, but he was also very earnest and persistent in his efforts to make a difference for the cause.

A television and radio marketing specialist, George started to parlay his contacts in the local business, media, and pro sports communities into support for HDSA. He also generated ideas for fundraisers and advocacy efforts.

In 2012, George became the HDSA-San Diego board president. Since then, he has devoted most of his work days to leading the chapter’s continuing efforts to raise awareness and obtain funds for research towards treatments and a cure.

That year, he presided over the chapter’s 12th annual gala, which raised a San Diego chapter gala record $155,000 for HDSA.

“Volunteering works both ways as I have learned that I get a great deal in return and dream of the day, which we are all encouraged about, that a treatment for HD will be discovered,” George says in his HDSA profile. “And of course, that day can’t come soon enough.”

After reading his profile, I e-mailed George: “Thank you for sharing your family's powerful and haunting story – and your message of hope. If more unaffected relatives of the affected helped out, as you do, we'd be much further along in this fight.”

Learn more about George and his advocacy in the photos below. To donate to HDSA, please click here.

George and Theresa Essig (right) with San Diego Chargers quarterback Philip Rivers (in blue tie) and Essig daughters and sons-in-law at 2009 HDSA-San Diego Celebration of Hope Gala (photo by Mike Nowak). The San Diego chapter's signature event, the Hope Galas have brought in over $1 million for care and cure of HD since 2001. 

George speaks at the April 2011 meeting of the San Diego HD support group (photo by Gene Veritas). Each year the chapter board meets once with support group members to discuss chapter activities.

George with daughter Julie and wife Theresa at December 2013 screening of the HD documentary Alive and Well (photo by Gene Veritas)

George addresses the crowd just before the start of the 2014 HDSA-San Diego Hope Walk on April 13 (photo by Gene Veritas). The event garnered more than $40,000 for HD care and cure.

Reaching out to the ‘HD family’ at the World Congress on Huntington’s Disease

As I returned on the plane from Brazil and the sixth World Congress on Huntington’s Disease, held September 15-18 in Rio de Janeiro, I was thrilled about my fortified connections to the emerging global movement to defeat HD.

I greatly expanded my contacts within the Brazilian HD community, which had the largest representation of HD family members, with more than 60 attendees.

After months of frequent contact via e-mail, phone, and Skype, I was delighted to meet in person Taíse Cadore, the president of the Associação Brasil Huntington (ABH), and neurologist Francisco Cardoso, M.D., Ph.D., two key organizers of the event. Along with Dr. Mônica Santoro Haddad, Cadore, Cardoso, and I have worked to raise the profile of HD in Brazil and to involve the government in improving the care provided to patients.

ABH volunteers helped put on the congress, staffed an information table, and attended many of the scientific and HD-family-oriented activities. Along with the organizing committee and many other Brazilians contributing to the event, the ABH volunteers made the congress a success.

In the coming days, I will prepare a comprehensive report on the congress, including a video of my presentation on coping strategies for living with the HD gene, plus many of the other presentations.

Taíse Cadore (photo by Gene Veritas)

Gene Veritas with (from left to right) ABH volunteers Carmen Faccio, Maria Eni Souza, Carmen Varalta, Majida, and Tereza Portigliotti and Zulay Final Romero of the Venezuelan HD association. The t-shirts say "embrace this cause." 

Cramming in activities

For now, I am focusing on the transition from the cultural environment of Brazil – my “other home” – back to my life in San Diego.

International journeys require intense, detailed preparation. This one proved especially demanding.

After a 25-year stretch in which I visited Brazil annually, including long periods living there, I declined to travel there in 2011 and 2012. Those years my time was taken up by my increasingly public HD advocacy and my added focus on the history of science, technology, and medicine in the context of the Huntington’s movement. The trip felt like a whirlwind: it included the congress, four presentations, other Brazil-related research, and visits with relatives and friends crammed into just ten days.

It didn’t help matters that my connection to Rio was delayed some 13 hours, obliging me to spend the early morning of September 13 sleeping on a cot in the Dallas-Fort Worth airport. The trip to Rio wound up taking 30 hours!

A life-affirming quest

This was not just another of my expeditions to Brazil.

Once again, I was on a mission to help defeat Huntington’s disease, the condition that, unless a treatment comes soon, will relentlessly attack my brain. In addition to helping with advocacy in Brazil and planning a bit of the congress, I spent more than 30 hours preparing the speeches I would deliver in Brazil.

The day before I left the U.S., I gave a 90-minute Skype interview to journalist Marcelo Leite, who published an article in the Folha de S. Paulo titled “‘It’s necessary to pass laws against genetic discrimination,’ says historian.”

The ABH circulated copies of the article at the congress. A radio reporter who had seen the article interviewed me and others. Senator Aloysio Nunes Ferreira, one of three senators representing the state of São Paulo, Brazil’s most populous and economically powerful state, wrote me a personal e-mail pledging to push for passage of such legislation in Brazil’s Congresso Nacional.

I felt a deeply visceral satisfaction meeting with so many of the HD movement’s advocates. It was emotionally wrenching to see people with HD and hear the affected, gene carriers, at-risk, and caregivers tell their stories.

Hugging my fellow “HD family” members from far-off lands or shaking their hands joined us in a lifelong, life-affirming quest.

Gene Veritas with actress and ABH volunteer Luiza Portigliotti 

Gene Veritas with Carlos and Eliezé Adriani of Campinas, Brazil

Stark challenges, seeking advice

One woman, a middle-aged dentist from Rio in the early stages of HD but still completely lucid, wanted to know about supplements and other remedies that I take.

The mother of Priscila, a 31-year-old Rio woman with pronounced chorea, the involuntary, dance-like movements produced by HD, asked how she might get her daughter into a clinical trial for the HD “vaccine” they heard was in development in California. The newspaper O Estado de S. Paulo featured Priscila and her family in an article about the world congress and HD.

Priscila's mom was referring to the gene-silencing approach at Carlsbad-headquartered Isis Pharmaceuticals, Inc., which, along with pharmaceutical giant Roche, hopes to start Phase I of the trial by the end of 2014. I explained that Isis and Roche had not yet announced the trial sites and suggested that she and her family should keep abreast of news on the project.

Others shared with me their stories of testing positive for the gene, the stark challenges of family planning, and learning that a potential future mate is at risk.

Priscila, a 31-year old Rio resident who suffers from HD (photo courtesy of O Estado de S. Paulo)

Priscila on the beach in Rio (photo courtesy of O Estado de S. Paulo)

In sync with the movement

During this trip, I reached many milestones.

I felt fully in sync with the HD movement, its values, and its supporters, as I took 13 congress participants and leading HD researchers to my favorite Rio steakhouse and bar; for the first time met Nancy Wexler, the dean of HD scientists; and delivered my speech on HD and bioethics and engaging with the emotion-charged audience at a college in São Paulo on September 21.

As waiter serves steak, Gene Veritas (right) converses with HD specialist Dr. Ed Wild, global HD advocate Charles Sabine, and HD drug-hunter Dr. Doug Macdonald at Café Lamas in Rio de Janeiro (photo by Alice Wexler).

I felt vindicated in my decision to go fully public about HD late last year and meld my professional and personal lives with my advocacy.

I smiled and got a warm feeling inside as I spoke of this big transition in my life with a long-time Brazilian friend and professional colleague.

As she observed, I was doing the right thing.

Gene Veritas (aka Kenneth P. Serbin) in Rio (photo by Tim Power)