Thursday, April 01, 2021

Overcoming a ‘heartbreaking’ moment for the Huntington’s disease cause (Coping with disappointing clinical trial results – Part I)

 

In the wake of two deeply disappointing clinical trial updates in just one week, the Huntington’s disease community is collectively grieving the loss of drugs that might have provided the first effective treatments for this incurable disorder.

 

As reported here, on March 22 Roche announced that it was halting dosing in the firm’s historic Phase 3 clinical trial of its gene silencing drug tominersen because of unfavorable efficacy data, as seen by an independent review committee.

 

On March 29, Wave Life Sciences revealed that a similar effort – gene silencing drug candidates in two small, earlier-stage trials – had failed to lower the level of the mutant huntingtin protein in trial participants.

 

Whereas Roche partner Ionis Pharmaceuticals’ success in using tominersen to reduce the protein represented a milestone and moment of euphoria in the HD community, the stall in the effort to transform this type of drug into an actual treatment in both the Roche and Wave programs has created one of the most frustrating moments of the last several decades.

 

With its usual resilience, the community and its leaders have responded quickly, organizing outreach events and furnishing resources to put the Roche results in perspective and provide ways to cope with the shock and disappointment.

 

Grieving because of lost hope

 

“It has been heartbreaking,” Katie Jackson, the president and CEO of Help4HD International, said of the Roche stoppage, which, she added, has “rocked the HD community.” Jackson’s husband Michael Hinshaw died of HD in 2019 at age 40, and she has three children at risk for being carriers of the HD mutation.

 

Jackson spoke during a March 24 panel discussion on Help4HD TV titled “Grief – When a clinical trial doesn’t go as hoped it is a loss.”

 

“I’m definitely grieving,” said Help4HD activist and podcast host Lauren Holder, 35, like me a carrier of the HD gene. The mother of two young at-risk children, Holder lost her father Stephen M. Rose, Jr., 62, to HD in January.

 

Holder said that she felt “extremely sad and disappointed and terrified” by the Roche news. The possibility of a treatment was “huge for us to have – to get so close to where it did and have all of the information so good on it” over the past several years, but then suddenly that hope “was taken away.”

 

HD gene carriers “don’t have time to just go back to the beginning” of another trial, “because that could mean symptoms” might have already started, she lamented.

 

“Everyone is human,” observed Help4HD vice president and CFO Katrina Hamel. “We all are feeling something because of this news.”

 

“I felt like someone punched me in the stomach,” said MaryAnn Emerick, an HD family member, in a March 25 webinar on the Roche announcement and grief sponsored by the Huntington’s Disease Society of America (HDSA), where she works as the manager of youth and community services. “I started hysterical crying.”

 

Emerick had built “more hope” in the potential of the Roche trial than she had realized, she added.

 

About 500 people took part in the webinar, including clinicians, scientists, social workers, and HD family members – a sign of both the impact of the Roche announcement and of community solidarity.

 

 

A slide from the HDSA webinar that focuses on the concept of ambiguous grief and compares the textbook-version stages of grief with how grief can actually be experienced by an individual. Presenting the slide is Jennifer Simpson, LCSW, HDSA assistant director of youth and community services (screenshot by Gene Veritas, aka Kenneth P. Serbin).

 

Tracking the project since 2008

 

I, too, have grieved the outcome of the Roche trial. I began tracking the program in April 2008, less than a year after tominersen developer Ionis (formerly Isis Pharmaceuticals) had initiated the search for a gene silencing compound. I reported on every key turn of the project, with many visits to the Ionis facility in Carlsbad, CA, about 30 miles from my house.

 

The prospect of taking an Ionis-Roche drug developed in my own community has long felt like a protective blanket shielding me from Huntington’s. Now, that blanket has been ripped away.

 

Like other HD family members, the Roche announcement has led me to relive the difficult moments in my family’s HD history, including my mother’s inexorable decline and then death in 2006. Since the day of the Roche news, I have aggravated the unhealthy, usually unconscious habit of clenching my teeth.

 

I do add my deep thanks to the chorus of gratitude for the participants in the Roche trial and their families and – once the data is analyzed in the coming months – for their contributions to a greater understanding of HD science. In Emerick’s words, “They are the foundation for the future.”

 

The team effort was not a ‘failure’

 

Other perspectives on clinical trials can perhaps help the community overcome the grief and disappointment.

 

In 2005, when I was preparing articles for the HDSA-San Diego chapter newsletter on a research project in San Diego sponsored by the Hereditary Disease Foundation, a scientist educated me on a key point: if a scientific experiment does not produce the desired result, that does not mean it failed. On the contrary, such an experiment is valuable in its own right because it brings forth new information and helps point the way for future experiments.

 

Clinical trials are scientific experiments, a fact underscored by the scientific and medical personnel at the HDSA webinar. Interestingly, nobody said “failure” at that event nor at the one by Help4HD.

 

Indeed, the Roche and Wave trials should not be considered failures – especially because of the very large team efforts involving not just the scientists and the participant families, but many kinds of support staff from inside and outside those firms.

 

Riding – and learning from – the clinical trial roller coaster

 

Emerick described another common feeling that can ultimately help the community move forward in the search for effective treatments: “I’m going on this roller coaster ride of emotion and feeling super-motivated and resilient and then all of a sudden just wanting to cry and wanting to know why – give us answers.”

 

Leading HD scientist Robert Pacifici, Ph.D., anticipated this scenario in February 2020. At that point, Roche was approaching the midpoint of its trial and, significantly, other clinical trials were also ramping up – as others do today.

 

“Getting to this stage – which we’ve all so been hoping for – is still a bit of a roller coaster ride,” Dr. Pacifici told me in an interview at the 15th Annual HD Therapeutics Conference, sponsored by CHDI Foundation, Inc., the nonprofit virtual biotech dedicated solely to finding HD therapies and headed by Pacifici. “You have to be able stay in our seats and weather the ups and downs. I think we’re well-poised for some great news, as some of these trials hopefully report out. Even a whisper of efficacy would be just amazing.”

 

However, there will also be “disappointments, where, despite our best attempts, some of the things that showed so much promise didn’t end up meeting their endpoints,” he cautioned. “But it’s going to be a learning roller coaster. So hang in there. Don’t lose hope.”

 

The HD-affected (and their caregivers) should keep informed about the trials by consulting their physicians, attending meetings of patient organizations, and keeping abreast of developments in such sources as HDBuzz and this blog, Dr. Pacifici advised.

 

Become knowledgeable, he urged, “so that you are not disproportionately spooked or elated when these bits of information come out.”

 

Many of us are scared. However, in the words of my “HD sister” Holder, now is the time to reach out to one another, and remember that the scientists have continued their quest.

 

Nobody has to ride that roller coaster alone.

 

(The second part of this series will examine other key programs in the Huntington’s disease drug pipeline.)

 

(Disclosure: I hold a symbolic amount of Ionis shares.)

Tuesday, March 23, 2021

Tough news for Huntington’s, other neurological disease patients: Roche halts dosing in historic clinical trial on signs of inefficacy

 

Calling it “tough news to share” and “even more difficult to receive,” pharmaceutical giant Roche announced on March 22 that it has halted dosing in the firm’s historic Phase 3 Huntington's disease clinical trial of its gene silencing drug tominersen, GENERATION HD1, because of unfavorable efficacy data, as seen by an independent review committee.

 

“The committee recently met for a pre-planned review of the latest safety and efficacy data from GENERATION HD1 and made a recommendation about the investigational therapy’s potential benefit/risk profile,” wrote David West, Roche’s senior director, for Global Patient Partnership, in a letter addressed to the international HD community. “Based on the committee’s recommendation, we will permanently stop dosing with tominersen and placebo in the GENERATION HD1 study.”

 

GENERATION HD1 began in early 2019, paused for several months to recalibrate dosing, and became fully enrolled in April 2020. Volunteers were to receive the drug over 25 months, and Roche had expected to finish the trial and report results in 2022. Tominersen developer Ionis Pharmaceuticals, Inc., Roche’s partner, had completed a Phase 1/2a trial of the drug (testing for mainly safety and tolerability) in 2017. That trial was so successful that Roche skipped a full-blown Phase 2 and went directly to Phase 3, GENERATION HD1.

 

West noted that the review committee’s recommendations resulted not from “any new emergent safety concern, but on a broad assessment of the benefit/risk” for those receiving the drug as compared to those getting the placebo.

 

This means that the drug demonstrated an “unfavorable efficacy trend,” an official of U.S. Roche’s subsidiary Genentech wrote me in an e-mail. If successful, the trial would have demonstrated that tominersen could slow, halt, or even reverse HD symptoms.

 

“This is brutal and I am absolutely devastated for our patients and families,” Jody Corey-Bloom, M.D., Ph.D., the director of the Huntington’s Disease Society of America (HDSA) Center of Excellence at the University of California, San Diego, wrote me.

 

Trial participants in Dr. Corey-Bloom’s clinic were among those taking part in GENERATION HD1. “I am glad that Roche will continue following patients for safety and clinical outcomes,” she added.

 

Veteran HD physician LaVonne Goodman expressed a similar sentiment. “Hope has been so very high for this drug; our community will feel not just disappointment, but real grief,” Dr. Goodman wrote me. “However, we’re accustomed to grief, and are resilient.  I think part of the community message should be that supporting each other is vitally important now.”

 

HDSA Chief Scientific Officer George Yohrling, Ph.D., called the news “devastating.” “HD families around the world had their hopes held high that this experimental drug could one day soon become an effective therapy for HD,” Dr. Yohrling stated. “While this is clearly not the news we wanted to hear, I am confident that in the coming weeks the Generation HD1 data will help the scientific community understand why tominersen did not meet its desired outcome.”

 

Robert Pacifici, Ph.D., the chief scientific officer for CHDI Foundation, Inc., the nonprofit virtual biotech dedicated to discovering HD therapies and a collaborator of Roche and Ionis, also commented on the development.

 

“Roche’s decision to discontinue dosing in most of its Huntington’s disease studies based on a recommendation from the unblinded [with access to data] Independent Data Monitoring Committee that periodically reviews study data is a very disappointing outcome,” Dr. Pacifici wrote. “However, knowing our colleagues at Roche we are confident that this decision has been made in good faith with the best interests of study participants uppermost in mind.”

 

 

No new safety concern caused the halt

 

The stop to the Roche trial underscores the fact that an effective treatment still eludes not only HD scientists, but also researchers of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and other neurological conditions.

 

The reviewers who recommended the halt to GENERATION HD1 work separately from Roche. The committee has not yet shared its specific reasoning or data with Roche.

 

“It is important to note that the recommendation is not based on any new emergent safety concern,” West’s letter stated.

 

Roche has notified the clinical trial sites in the 18 participating countries of the halt. The sites are contacting the 791 symptomatic volunteers who had enrolled in the program.

 

The participants were receiving intrathecal (spinal) injections of tominersen or a placebo. Participants in GEN-EXTEND (an extension study for participants coming from any Roche HD study) will also no longer receive doses.

 

“It is our intention to provide as much information as we can to the community, which at this time is limited until we have accessed and analyzed full data,” West’s letter explained.

 

West acknowledged “the tremendous contribution of the families who are participating in these studies, as well as the broader Huntington’s community for their collaboration.”

 

Next steps depend on the data

 

Although Roche has stopped giving tominersen to the volunteers, the trial has not yet ended.

 

“The studies will remain ongoing (without further dosing in GENERATION HD1 and GEN-EXTEND) and it is intended that study participants will be followed by their physicians for safety and clinical outcomes,” West stated. Roche has not provided a timeline for the remainder of the work to be completed.

 

A Q&A appended to West’s letter states that “Roche remains committed to the HD space and our studies are continuing,” and data from GENERATION HD1 “will advance our understanding of tominersen and inform research for other disease modifying treatments.” It adds: “In addition to tominersen, the Roche family of companies is investigating gene therapy approaches to treating Huntington’s disease.”

 

The conclusions about GENERATION HD1 – and possible next steps by Roche and Ionis­­ – will depend on the analysis of the independent reviewers’ explanations and all of the massive data from the Phase 3 trial.

 

As Dr. Pacifici noted, only when data from the independent review committee has been “shared with the wider HD community” will it become possible to “form a scientific opinion” about the halting of the trial.

 

A perplexing result

 

Ionis held a public conference call on March 22 to answer questions about the Roche announcement.

 

“This is the largest Huntington’s trial ever conducted,” stated Ionis CEO Brett Monia, Ph.D. “It was conducted on a wealth of information.”

 

Monia stated that, “while we are saddened by today’s outcome, we are committed to the HD community and focused on delivering treatments for this and other devastating neurological diseases.”

 

Monia added, “Although this is a disappointing setback for Ionis and the HD community, we are confident in the potential of our technology platform to address many neurological diseases.”

 

Various questioners on the call asked Dr. Monia and Ionis scientists to speculate about the reasons for the halt and future potential approaches using the company’s technology (antisense oligonucleotides, or ASOs), but the Ionis officials emphasized that answers are premature without access to the data.

 

“We are still strong believers in the ASO approach,” Dr. Monia asserted.

 

However, Ionis Chief Scientific Officer Frank Bennett, Ph.D., the long-time coordinator of the firm’s HD program, added that the news of the potential ineffectiveness of using an ASO to reduce the amount of huntingtin protein in patients was “perplexing and disappointing to us,” leaving many unanswered questions.

 

Eric Swayze, Ph.D., Ionis’s executive vice president for research and one of the developers of the ASO, reminded the participants on the call of a fundamental reality of HD: “It’s a complex disease.”

 

Dr. Monia added that “one silver lining” in the halt to GENERATION HD1 was that it did not, as noted above, result from a concern about safety.

 

Diversification necessary

 

Although the pioneering Roche-Ionis program had electrified the HD world with the hope of the first effective treatment, the HD research community has also deliberately diversified the approaches to treating HD.

 

Thus, companies like Triplet Therapeutics, Inc. have leveraged publicly available knowledge gained from the Roche/Ionis program and others to plan their own, unique drug development strategies.

 

Triplet aims to start a clinical trial in the second half of this year for a potential drug targeted at stopping the mutant huntingtin gene’s tendency for continued expansion with age. That expansion compromises brain cells and triggers disease. In this respect, HD is known as a repeat expansion disorder (RED), with the triplets of the genetic code CAG recurring too many times and thus causing disease.

 

As a Triplet scientist explained last year, the Roche/Ionis approach is like “putting a brake” on the disease, whereas Triplet’s ASO will target the expansion of the gene and therefore seek to “remove the foot on the gas.” (Click here to read more).

 

Using the same mechanism, in addition to HD, Triplet hopes to develop transformative treatments for many of the more than 50 other REDs. For REDs of the central nervous system, it would use the same drug as for Huntington’s.

 

Although unavailable for comment on the Roche announcement, Triplet executives offered encouragement in an e-mail to me: “Triplet’s thoughts are with the HD community, and our clinical development plans in HD and other repeat expansion disorders remain on track and unchanged.”

 

As one scientist wrote me (and as I also felt), the Roche announcement was like a punch to the gut. However, I am also heartened by the potential of other clinical trials like Triplet’s. (I will further explore the implications of the Roche trial halt in upcoming articles.)

 

To echo Dr. Goodman’s words, our community and its scientists are indeed resilient.

 

(For more on the Roche announcement, see the article in HDBuzz).

 

(Disclosure: I hold a symbolic amount of Ionis shares.)

Sunday, March 14, 2021

Blog article No. 300: who exactly is Gene Veritas?

 

On January 10, 2005, I began the first post in this blog with a simple but consequential sentence: “My name is Gene Veritas and I am at risk for Huntington’s disease.”

 

Today, 16 years and two months later, after my mother’s death from Huntington’s at age 68 in 2006 and my own long struggle to avoid disease onset, I am writing my 300th post.

 

Now 61, I never expected to get this far. Starting in her late 40s, my mother’s symptoms left her progressively unable to care for herself and ultimately bedridden. And I inherited from her the same degree of mutation in the huntingtin gene – which I long thought portended the same fate.

 

As I have noted often in recent years, I feel extremely lucky to remain asymptomatic. Although there is (as yet) no genetic test available to individuals to pinpoint the reason, researchers have discovered key modifier genes that slow or hasten onset among people with identical mutations (click here to read more). Also, as doctors and researchers have observed, my efforts to lead a healthy lifestyle likely have also helped.

 

In the early years of the blog, writing under the protection of my Gene Veritas pseudonym, I focused mainly on my family’s struggles with the many medical and psychosocial ramifications of HD. More recently, with the tremendous advances in HD research of the past decade, I have emphasized the science and the advent of crucial clinical trials. Those trials have brought unprecedented hope for the HD community.

 

However, in the whirlwind of HD advocacy and writing, I have not paused to reflect on the deeper meaning of my alias. Even after I went fully public as Kenneth P. Serbin nine years ago in an article in The Chronicle of Higher Education, I am still widely known in the HD community as Gene Veritas.

 

I have relished explaining a pen name that has become my trademark. In my HD work, I actually prefer the pseudonym, which not only intrigues people but also instantly focuses our interaction on the profound implications of Huntington’s.

 

To mark my blogging milestone, I thus want to clarify two things: who exactly is Gene Veritas? And what does that name mean?

 

A college professor and family man

 

Huntington’s, as a 100-percent genetic disorder, always involves stories about families.

 

After the news of my mother’s diagnosis blindsided my wife Regina and me in late 1995, our life plans changed dramatically. A future as my potential caregiver has loomed over Regina ever since. She is ever thankful about my delayed onset.

 

We forged ahead as best we could. Over the past two decades, we have brought our HD-free daughter Bianca to the threshold of adulthood. Bianca expects to graduate from college in 2022.

 

I am in my 28th year as a history professor at the University of San Diego, and Regina works as an instructional coordinator for the San Diego Unified School District.

 

As a family, we have been active in the local chapter of the Huntington’s Disease Society of America. In 2017, we traveled to Rome for one of the most extraordinary moments in our journey with HD, “HDdennomore: Pope Francis’ Special Audience with the Huntington’s Disease Community in Solidarity with South America.”

 

In the doctor-recommended enrichment and exercise that I practice, I have included the canine member of our family, our cockapoo Lenny, with long walks on diverse routes through our neighborhood.

 


Gene Veritas (aka Kenneth P. Serbin) with wife Regina, daughter Bianca, and dog Lenny (family photo)

 

Representing our common struggles

 

I began this blog under “Gene Veritas” because I lived in the “terrible and lonely HD closet,” fearing discrimination on the job and in healthcare and insurance matters. I built what I have described as an “absolute firewall” between my HD reality and the rest of my life.

 

In February 2011, I took a major step out of that closet by delivering the keynote speech at the “Super Bowl” of HD research, the Sixth Annual Huntington’s Disease Therapeutics Conference, sponsored by CHDI Foundation, Inc., the nonprofit virtual biotech solely dedicated to finding HD treatments. It was held in Palm Springs, CA.

 

About 250 prominent scientists, physicians, drug company representatives, and others listened to my speech, which was titled “Blog Entry 85 … Unmasking the World of Gene Veritas: An Activist Copes with the Threat of Huntington’s Disease.” (I referred to an “entry” instead of “post,” because of the diary-like nature of the blog in the early, anonymous years. Now I use the term “article,” because the posts have become more in-depth and sometimes run several thousand words or more.)

 

As I wrote in an article about that key moment, despite revealing my real name to the audience, my penname “‘Gene Veritas’ will still live on in cyberspace.[…] Through its anonymity and universality, it symbolizes the common struggles of families threatened by HD and numerous other neurological and genetic diseases.”

 

Indeed, in many talks since then I have introduced myself with both my real name and pseudonym.

 

‘The truth in my genes’

 

I explain to people that “Gene Veritas” means “the truth in my genes.”

 

A “gene” is a sequence of DNA, the code that programs our development as humans and gives us particular characteristics. “Veritas” is Latin for “truth.”

 

The truth of my future lies in the mutant huntingtin gene that I inherited from my mother.

 

I also have a personal connection to “veritas”: it forms part of the motto “lux et veritas” (light and truth) on the seal of my alma mater, Yale University.

 

The connection to Yale bubbled up from my subconscious while I was searching for a pseudonym. Surely Yale also came to mind because of the solidarity, advice, and assistance I have received from fellow alumni (click here, here, and here to read more).

 

As one observed, because of the devastation caused by HD, the pseudonym can also represent a grim pun on the school motto.

 

We are all Gene Veritas

 

On March 8, I participated in an online interview conducted by HD global advocate Charles Sabine and Simon Noble, Ph.D., CHDI’s communications director. They wanted to learn more about the Gene Veritas facet of my life.

 

Dr. Noble asked me whether I had an alter ego and other identities, in line with the ideas of 2010 keynoter and graphic novelist Steven Seagle, who has addressed his family’s way of confronting Huntington’s by juxtaposing the reality of disabling HD with the fantasy of Superman.

 

“Gene Veritas” is my alter ego, I said.

 

So, Dr. Noble wanted to know, how did the Gene Veritas alter ego protect me? Did it allow me to do other things? Did I become a different person in some respect? Were there positives to being Gene Veritas?

 

“Absolutely,” I responded. “Being anonymous for so many years allowed me to be completely honest about Huntington’s disease. Those first years of the blog were a complete explosion of HD honesty – talking about the feelings, talking about the discrimination, talking about the anger, the hurt, the pain, worrying about my mother, seeing my mother die from the disease. Those early years were really, really hard.”

 

This blog and “Gene Veritas” have also served as coping mechanisms, I added, and they allowed me to build awareness about HD.

 

“But how to build awareness anonymously?” I continued. “It’s like a contradiction in terms. That’s why ‘Gene Veritas’ became so important, because I was somebody. I couldn’t be Ken Serbin, but I could be Gene Veritas.”

 

Pondering further the universality of my pseudonym, I observed: “It’s my story, but it’s really the story of the HD community. Anybody could be Gene Veritas in the HD community. Because I think we’ve all been at one point or another a kind of Gene Veritas, at least when we first find out about Huntington’s. It’s representative. It’s something that has a broad meaning to it.”

 

Writing the history of the HD movement

 

In this blog, my CHDI keynote, and other speeches, I have documented the new and harrowing human experience of living in the gray zone between a genetic test result and onset of a disease.

 

In my CHDI speech, I showed a slide with a simple breakdown of main blog topics to that point. Information about the disease and research was the leading topic, followed by articles on my mother, fear of onset, and coping.

 

I will do a more fine-grained content analysis of posts for an academic article on the blog as a coping mechanism, fount of information for the HD community, and source of insight into the fight against HD and the search for therapies. I will submit the article to a scientific or medical journal.

 

I am also planning a book on the history of the Huntington’s disease cause, tentatively titled “Racing Against the Genetic Clock: A History of the Huntington’s Disease Movement and the Biomedical Revolution.” The blog will serve as a considerable primary source (a document or other material produced by a participant in a historical event) for my research and/or future historians of the HD cause.

 

In academic year 2021-2022, I will dedicate an expected sabbatical (a leave from teaching and other on-campus duties) to the book project. I will consult researchers, physicians, and members of the HD community about the key themes.

 

I earnestly hope to recount in this blog and my book the achievement of effective treatments for HD.

Thursday, February 25, 2021

Getting the COVID-19 vaccine and a new exercise bike to keep stable in the fight against Huntington’s disease

 

In my fight against Huntington’s disease, I have strived to delay the inevitable onset by working hard to keep my overall health stable. This strategy has included avoiding potential shocks to my system.

 

Now the leading cause of death in the United States, COVID-19 poses a threat to all of us. As a 61-year-old HD asymptomatic gene carrier, I have religiously followed recommendations on social distancing, mask use, and handwashing.

 

As a university professor, I have taught online since March 2020. The pandemic has rocked universities’ finances and employees’ benefits. Despite serious precautions by the schools, the coronavirus has surged among some students, including at my campus, the University of San Diego.

 

On February 6, I got a last-minute opportunity to get vaccinated with the Moderna COVID-19 vaccine. A San Diego nonprofit clinic that was following guidelines to first vaccinate individuals 65 and over announced around midday that not enough people from that group had responded, thus making available extra doses that needed to be injected that day. Educators and healthcare workers were invited to get that first of two doses.

 

My wife Regina, an instructional coordinator for the San Diego Unified School District, and I jumped at the chance. After a two-hour wait, including filling out forms and questionnaires, we received our shots! We were jubilant. Getting vaccinated also felt like an extra gift for Regina: February 6 was her birthday.

 

 

Gene Veritas, aka Kenneth P. Serbin, receiving an injection of the Moderna COVID-19 vaccine (selfie by Gene Veritas)

 

As one of the tens of millions of Americans now at least partially vaccinated, I am protecting not only my health, but also limiting the spread of the pandemic. (For an expert discussion of the ethics of COVID-19 vaccination, including the phenomenon of “vaccine guilt,” click here.)

 

I was also proud to get the Moderna vaccine because its RNA-based approach resembles some of the treatment strategies being tried in HD clinical trial programs. Furthermore, the scientist-written HDBuzz website has urged HD-affected individuals to get vaccinated for COVID-19.

 

Though I had a sore arm and felt a queasy for a couple of days, I have felt normal since. We are scheduled to get the required second shot on March 6. I also have participated voluntarily in the federal government’s V-safe After Vaccination Health Checker, a mobile phone app including questions about pain and other potential side effects.

 

An innovative, ‘neurobic’ spin bike

 

Four days after our COVID shots, technicians delivered and set up our long-awaited new exercise machine, the Peloton Bike+, which has a screen for watching online classes.

 

Regina and I have always prioritized exercise. This has become ever more important as we have aged. When we had a backyard pool built in 2009, I insisted on installing a Fastlane swim device so that I could exercise vigorously.

 

I have varied my exercise – swimming, walking, riding a stationary bike – to focus on different parts of the body.

 

In general, avoiding physical and mental routine can reinforce brain and overall health. This has led me to practice “neurobics,” a word that combines words “neurons” and “aerobics.” Such brain workouts can include something as simple as engaging with interesting people or taking a different route every time I walk. Neurobics can increase levels of the critical brain nutrient BDNF, brain derived neurotrophic factor. (Click here to read more.)

 

After the start of the pandemic, we noted the extensive TV advertising for Peloton (which even became the subject of a recent Saturday Night Live skit poking fun at the motivational online workouts).

 

The Peloton bike and other online exercise apps that feature live and recorded exercise classes are an innovative, neurobic way of connecting with coaches and others. Users can expand their physical and mental horizons with the wide variety of online cycling classes, strength exercises, stretch classes, yoga, and other activities.

 

 

Gene Veritas riding the Peloton Bike+ (photo by Regina Serbin)

 

We have found the Peloton Bike+ and the app to be far superior to our previous exercise bike, which had begun to deteriorate. A spin bike, the Peloton allows for a more versatile workout.

 

In the psychologically devastating social isolation of the pandemic, the Peloton is also allowing us to thrive indoors. Despite a significant sticker price, the bike makes sense budget-wise, since the money from Regina’s cancelled gym membership goes to a monthly payment plan.

 

Subtle impairments predate onset

 

On February 16, I received a stark reminder of how Huntington’s disease can impair gene carriers, however slightly, in the years leading up to an actual clinical diagnosis.

 

I attended an online presentation by Paul Gilbert, Ph.D., a professor and the chair in the Department of Psychology at San Diego State University, to the University of San Diego Neuro and Psych Research Club. Titled “Neuropsychological Changes in the Premanifest and Manifest Stages of Huntington’s Disease,” Dr. Gilbert’s talk highlighted some of the key findings in his ongoing research on this topic, including data from a 2020 article by his team in the journal Cognitive and Behavioral Neurology.

 

Premanifest HD involves the period before a neurologist can actually observe a gene carrier as having experienced the onset of the disorder’s typical motor, cognitive, and/or behavioral symptoms, stated Dr. Gilbert. In the past, physicians only saw the motor symptoms – involuntary movements and unstable gait, for example – as signs of the malady

 

Using verbal learning and memory tests, the research has demonstrated that these individuals can develop subtle cognitive symptoms – in particular, memory loss – ten to fifteen years before the formal diagnosis, Dr. Gilbert explained. The memory deficits increase dramatically after HD onset, he added.

 

“It really argues that we as clinicians need to be looking at not just the motor symptoms to make a diagnosis of Huntington's disease, but really starting to look at cognitive symptoms,” Dr. Gilbert asserted.

 

That position echoes the general trend towards a view of Huntington’s as a multi-symptom disease over the past several decades.

 

Statistical versus clinical signs

 

As a regular participant in research studies, I have performed a number of the tests that Dr. Gilbert described.

 

During the Q&A, noting that gene carriers like me worry about where we stand on the road to onset, I asked Dr. Gilbert whether the premanifest impairments hamper “actual functioning,” for example, daily activities such as driving, balancing a checkbook, and communicating with others.

 

“They’re statistically impaired, but they’re not clinically impaired,” Dr. Gilbert observed about the gene carriers in the research studies. The deficits are “very subtle” and can only be picked up on testing, he added.

 

Nevertheless, he added that his research has also determined that subtle memory impairment does have a “measurable but quite mild” impact on activities like handling finances or taking medications, but that only after onset does the disease seriously interfere with daily living.

 

(Dr. Gilbert’s work also echoes the recent landmark study of young HD gene carriers, ranging in age from 18-40 and illustrating no significant cognitive of psychiatric decline. Click here to watch Dr. Gilbert’s 2018 presentation on HD to University of San Diego students.)

 

Anticipating a brighter future

 

With the pandemic and the worst economic crisis since the Great Depression, I am very fortunate to have a job and work remotely.

 

Because an estimated 20 percent of HD onset results from non-genetic factors, my imminent protection from COVID-19 and anticipation of new neurobic adventures with the Peloton can help me maintain stable health.

 

They certainly have helped me to feel optimistic about the future – for the first time in a year. I am also looking forward to news on the key HD clinical trials in progress.

 

Although we recognize the long-term social impact of the pandemic, Regina and I are especially looking forward to a healthier and happier 2022 for all, and the chance to travel: we hope to attend my 40th college reunion, celebrate our 30th wedding anniversary, and watch our HD-free daughter Bianca graduate from college.

 

We are thankful for every moment of life.

Monday, February 08, 2021

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

 

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

 

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

 

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

 

The arduous years

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

Tons of luck, and some positive strategies

 

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

 

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

 

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

 

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

 

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

 


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

 

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

 

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

 

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

 

Gaining enlightenment about HD

 

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

 

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

 

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

 

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

 

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

 

Pride

 

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

 

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

 

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

 

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

 

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

 

Pope Francis displayed great love and mercy for our community.

 

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

 

Tributes, and imagining a world without HD

 

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

 

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

 

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

 

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

 

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

 

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