Scientists interacting with Huntington’s disease patients in the quest for therapies

 

In the quest for Huntington’s disease therapies, scientists have found key intellectual fuel for understanding the genetics of this fatal neurodegenerative disorder and developing therapies.

 

A brainstorming strategy became the trademark of the HD-focused Hereditary Disease Foundation (HDF), founded in 1974 by leading Los Angeles psychoanalyst and HD activist Milton Wexler as an offshoot of the Huntington’s Disease Society of America (HDSA).

 

Wexler organized multidisciplinary small workshops of scientists aimed at spontaneous discussion – as opposed to dry scientific presentations with slides – to search for the HD gene and develop treatments (click here to read more).

 

Allan Tobin, Ph.D., the former director of the Brain Research Institute at the University of California, Los Angeles (UCLA), ran hundreds of workshops for the HDF and later for CHDI Foundation, Inc. (CHDI), today the main private funder of HD therapeutic research.

 

Involving the affected

 

Many scientists have had little or no contact with HD families, so the HDF has included individuals from those families in its workshops. I was exposed to this approach in 2012, when Dr. Tobin transformed my desire to simply blog about a CHDI workshop into an event that included a 90-minute discussion of HD’s health and social ramifications based on my family’s story.

 

On the morning of January 30, I once again interacted with HD scientists, answering an invitation from HDF CEO Meghan Donaldson to offer my “perspective as both a family member and someone who is gene-positive,” aiming to help connect researchers “to the patients and the disease and to strengthen their resolve for finding a treatment.”

 

I not only spoke about my HD journey but also exchanged ideas with the scientists about their mission of developing therapies and also the many challenges faced by the HD community.

 

For me, exploring science with researchers serves as both mental enrichment and coping mechanism as I strive to forestall what research predicts will be my inevitable HD onset. Of course, I hoped to contribute to the scientific mission.

 

At the workshop: seated, from left to right, Mahmoud Pouladi, M.Sc., Ph.D., Osama Al Dalahmah, M.D., Ph.D., Ashley Robbins, Gene Veritas (aka Kenneth P. Serbin), Sarah Hernandez, Ph.D., William Yang, M.D., Ph.D. Standing, from left to right, Xinhong Chen, Andrew Yoo, Ph.D., Anton Reiner, Ph.D., Baljit Khakh, Ph.D., Nicole Calakos, M.D., Ph.D., Ed Lein, Ph.D., Beverly Davidson, Ph.D., Nathaniel Heintz, Ph.D., Harry Orr, Ph.D., Leslie Thompson, Ph.D., Myriam Heiman, Ph.D., Shawn Davidson, Ph.D., Steven Finkbeiner, M.D., Ph.D., Roy Maimon, Ph.D. (photo by Julie Porter, HDF) (Click on the image to enlarge it.)

 

Pondering modifier genes and a proactive approach

 

My 80-minute encounter with 20 scientists kicked off the two-day HDF Milton Wexler Interdisciplinary Workshop, held at the Huntley Hotel in Santa Monica, CA.

 

To provide background, before the meeting HDF Director of Research Programs Sarah Hernandez, Ph.D., sent the participants a copy of my article “Striving for a Realistic and Unapologetic View of Huntington’s Disease” from the Journal of Huntington’s Disease.

 

With the HDF’s permission, I recorded my remarks and Q & A with the scientists. As is customary, the confidential, scientific portion of the workshop was not recorded, to encourage uninhibited brainstorming.

 

After Dr. Sarah Hernandez introduced me, I gave an overview of my family’s fight against HD, including my mother’s diagnosis with the disorder in 1995, the genetic test revealing my risk in 1999, my gradual exit from the “terrible and lonely HD closet,” and strategies for delaying onset.

 

I discussed the possible key role of modifier genes in enabling me to reach the age of 64 still fully functioning – in contrast with my mother, whose symptoms began in her late 40s, ending with her death at the age of 68 (click here to read more).

 

Just before the meeting, I had discussed with two of the scientists that “maybe I should get my genome sequenced and find out if I actually have any of those modifier genes,” I told the scientists.

 

I noted, however, that no routine genetic tests exist for these genes and that establishing them might “open a whole new Pandora's box of bioethical considerations,” given the potential for unsettling messages. We'd have to have new protocols.”

 

“So, yes, I think it might be good to have those tests, but we've got to think very carefully about jumping into that,” I said. “But maybe for science, I could do my own whole genome sequence and write a blog article about it and analyze my modifier genes.”

 

I stressed that a “proactive approach is absolutely essential.” That option was unavailable to my mother, the first person to develop HD in an extended family with no knowledge of the disease.

 

Seeking to manage HD

 

The scientists probed various facets of my family’s HD experience and my advocacy.

 

I explained the importance of the HDSA-San Diego support group in providing vital information about such matters as genetic testing and obtaining long-term care insurance. I also discussed my timeline for testing and how I did so anonymously. I reflected on how my colleagues at the University of San Diego reacted positively to my exit from the closet and the full-throated advocacy that I could now pursue.

 

The concerns about discrimination led me to underscore the importance of the Affordable Care Act and the Genetic Information Nondiscrimination Act in eliminating discrimination against those with preexisting conditions.

 

Some wanted to know about the very difficult social and psychological challenges involved in genetic testing, and how to convince those worried about HD to reach out to medical professionals. 

 

Given how devastating the discovery of HD in a family can be, I advocated a “gentle” and gradual approach to getting people involved, recalling that research studies such as Enroll-HD allow people to participate anonymously and without knowing their genetic test results.

 

I pointed out that, despite the fear and devastation associated with HD, today the HD community has real hopes for clinical trials of HD-specific remedies. Such hope did not exist a quarter-century ago. As I tell younger people just starting their struggle against HD, although “there may not be the magic bullet,” HD might ultimately be “managed like other diseases are managed like heart disease, diabetes, and HIV.”

 

Involving presymptomatic people in trials

 

I was both humbled and thrilled that the scientists wanted my observations on various aspects of the search for therapies.

 

In my opening remarks, I had stated that, in comparison with the start of my HD journey in the late 1990s, thankfully it has been harder for me to track the progress because of so many research and clinical trial programs. In her introduction, Dr. Hernandez noted that I am at work on a biosocial history of the HD movement.

 

UCLA neuroscientist Baljit Khakh, Ph.D., asked whether I could identify “errors” to be avoided or “strengths” to be reproduced, as well as trends worth noting.

 

In response, I expressed my frustration about the lack of opportunity for presymptomatic gene carriers like me to participate in clinical trials. The now defunct Triplet Therapeutics, Inc., had planned such a trial, I observed, and that the Alzheimer’s disease field has had such a trial.

 

“We're a valuable resource,” I said, recognizing that such trials require approval by the U.S. Food and Drug Administration and also involve bioethical and financial considerations.

 

However, I also observed that “the field's done a great job of trying to diversify [drug] targets,” because of the many types of approaches under research.

 

Addressing the cognitive deficit

 

Nathaniel Heintz, Ph.D., of The Rockefeller University asked about the importance of clinical trials to test drugs to treat just symptoms, without modifying the course of the disease. Treatments developed for other diseases, like Parkinson’s, benefit millions, he noted, but does HD as a rare disease face a greater challenge to attract trial volunteers?

 

I observed that HD now has three treatments for chorea, the involuntary, dancelike movements experienced by many of the affected.

 

However, I also pointed out that HD clinical trials are very U.S.- and Europe-based, avoiding important countries such as Brazil, which was not included in Enroll-HD. I observed how HD families in Brazil and other parts of the world are “desperate to participate in clinical trials.”

 

Xinhong Chen, a lab researchers at the California Institute of Technology, touched on another facet of Dr. Heintz’s question: what symptoms do people most want treated to improve their quality of life?

 

I pointed to the importance of reducing the “cognitive deficit” that occurs with HD and prevents people from engaging in daily functions, caring for themselves, and communicating with others. I added that I had hoped to take pridopidine, a pill developed for this purpose. Sadly, the pridopidine trial failed in April 2023.

 

Andrew Yoo, Ph.D., of Washington University in St. Louis, wanted to know how to overcome the lack of interest in HD and related research in his native South Korea.

 

The leadership of the HDF, CHDI, HDSA, and the Huntington Study Group (HSG) should push for greater “diversity” on the international level, I said, suggesting that the HSG could send a delegation to South Korea. Also, advocates and medical personnel can spur action on HD, Alzheimer’s, and other neurodegenerative diseases by alerting people to the caregiving crisis, which is global, I observed.

 

The scientists get down to business

 

I was energized by my exchange with the scientists.

 

After my session, the workshop participants took up the main business of the rest of that day and the next: “cell type specific biology in Huntington’s disease.”

 

That activity was chaired by William Yang, M.D., Ph.D., of UCLA, Myriam Heiman, Ph.D., of the Massachusetts Institute of Technology, and Steven Finkbeiner, M.D., Ph.D., of the University of California, San Francisco.

 

Through their brainstorming – the first session of which I observed – the participants aimed to advance ideas for HD therapies.

 

On January 29, I lunched with Dr. Yang, gave a slide presentation on my advocacy to his research team, and toured his lab. I also interviewed Dr. Yang on his latest research.

 

Stay tuned for my next article: Dr. Yang’s long interest in HD and his enthusiastic outlook for potential therapies.

 

Disclosure: the Hereditary Disease Foundation covered my workshop travel expenses.

 

Gene Veritas (left) with Dr. William Yang in his UCLA office. In the background: a medium spiny neuron, one of the brain cells most affected by Huntington’s disease (photo Nan Wang, Ph.D., of the Yang Research Group).

Lessons from the Maui wildfires for human solidarity and the fight against Huntington’s and other diseases

 

In late June – vacationing in the balmy Hawaiian town of Lahaina – my wife Regina and I snorkeled at Pacific Ocean coral reefs teeming with marvelous aquatic life, dined on succulent seafood, and recharged our emotional batteries after a difficult first half of 2023.

 

We had celebrated our 30th wedding anniversary by traveling to Hawaii for the first time, to the islands of Kona and Oahu, in March 2022. I had never expected to reach my early 60s healthy: I carry the deadly gene for Huntington’s disease, which took my mother at 68. Inspired by the spirit of aloha, we returned with our daughter Bianca in July 2022, this time to Lahaina, on the island of Maui, to celebrate her college graduation.

 

Now, we are alarmed by the massive destruction of Lahaina’s historic core on August 8 by wildfire, and the impact on the rest of Maui. As of August 14, 96 people had succumbed to the fire. This was the deadliest wildfire in the U.S. in over a century, resulting from sweeping long-term human-led changes to the Hawaiian landscape, climate change, and seeming poor preparedness by public officials.

 

We were heartbroken to learn of the deaths and how the fire burned down museums, restaurants, and stores that we had visited on Front Street, the historic main drag dating back to Lahaina’s time as the capital of the Hawaiian kingdom and whaling center in the 1800s. More than 2,000 buildings were destroyed or damaged.

 

We were heartened to see how Hawaiians were coming together, with help from the mainland, to assist one another and express hopes for rebuilding.

 

Such devastation, I believe, is another reminder to strive for human solidarity in the face of global climate change, war, and disease – including devastating neurodegenerative disorders like HD and Alzheimer’s and the threat of future pandemics.

 

Gene Veritas (aka Kenneth P. Serbin) with exhibit of whaling equipment at the Lahaina Heritage Museum in the Old Lahaina Courthouse (photo by Regina Serbin). After the fires, only a shell of the building remains.

 

An overpowering nature

 

With the coronavirus pandemic, the war in Ukraine, and the climate crisis, the history of humanity and the environment may have reached a tipping point.

 

In July, as the world experienced record temperatures, United Nations Secretary-General António Guterres declared that global warming has become “global boiling.”

 

The fires at Lahaina and other parts of Maui reminded Regina and me of the overpowering nature of wildfires in California, which in recent decades have burned ever more acres, taken lives, and forced evacuations.

 

In 2003, during the massive, deadly Cedar Fire, we and thousands of other families were forced to leave our homes in our San Diego residential neighborhood homes; for two long days we wondered whether we would have a home to return to. We saw flames rising 40 or 50 feet into the air as we drove off in our vehicles. Several homes in our neighborhood burned down. Many other neighborhoods also had to evacuate.

 

Significantly, this fire was not restricted to the backcountry but reached into the suburban neighborhoods of the city of San Diego.

 

In Hawaii, a group of youth are suing the state’s Department of Transportation over climate change. In another case involving young people, on August 14 a Montana judge ruled..that the state's failure to consider climate change when approving fossil fuel projects was unconstitutional.

 

Regina and I are exploring ways to lessen our impact on the environment.

 

Keeping the momentum on disease research

 

There is no arguing with nature.

 

With this new reality, as the climate crisis threatens to deepen, societies could have fewer resources for combating disease because of the need to prioritize saving the environment.

 

There is also no arguing with biology. I have endeavored to avoid HD onset through building new avenues of enrichment and building meaning and purpose, including my new interest in the history and culture of Hawaii – stimulated yet further, though in a tragic sense, with Lahaina’s traumas.

 

After our trip to Lahaina, I underwent surgery on my left hand to repair the damage wrought by another biological reality: arthritis and tendonitis. The hand had become painful and weak. I wore a cast for a month, and am now undergoing physical therapy.

 

As with a hip or knee replacement, I am hoping that the operation will restore full use of my hand for many years, and to enable me to work, exercise, and carry out daily activities to reinforce my overall health in the fight against HD.

 

Not having to worry about the hand will also provide an important psychological boost.

 

Our concerns about the environment come precisely as the search for cures for neurodegenerative diseases got some good news: for the first time, the FDA has approved two drugs that have shown efficacy in slowing the progression of Alzheimer’s (click here and here to read more).

 

We need to have that momentum carry over to HD and other diseases. After having to step away from advocacy earlier this year, followed by weeks of inactivity due to my operation, I hope to return to regular reporting of the quest for HD therapies.

 

Gene Veritas recovering from hand surgery (photo by Regina Serbin)

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.

Accentuating the positive: Olympic medalist Sarah Winckless’s strategy against Huntington’s disease

As a bronze medalist in rowing in the 2004 Summer Olympics in Athens and chair of the highly successful British athletes’ commission in the 2012 London games, Sarah Winckless pursued her goals based on strenuous training, teamwork, and effective thinking.

However, Sarah faces a challenge far more daunting than most Olympians could imagine.

Since 1997, when she learned at just 22 that she carries the gene for Huntington’s disease, Sarah has faced the difficult reality of knowing that she will likely follow in the footsteps of her HD-afflicted mother Val, who requires full-time care.

Sarah has kept upbeat by focusing on athletics and her major leadership roles in the British sports and HD communities.

Huntington’s is always a family story. Sarah was the first of four siblings to undergo genetic testing. When Sarah began to feel isolated from her two brothers and sister after all three tested negative for HD, she turned once again to the “thinking challenge” she had learned in sports.

“Suddenly my siblings didn’t know what is was like to open the door of your genetic counselor and know that you’ve got a bad result,” Sarah told an audience of several hundred scientists, drug company representatives, and Huntington’s disease advocates the evening of February 24 in her keynote address at the Ninth Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc., in Palm Springs, CA. “And I didn’t want them to know that. But it made me different. It separated me.”

Sarah said that she “hated” herself for “thinking and feeling that way.”

“I had to choose a thought that brought me back in, that made me part of my family – they’re so important to me,” she continued. “And I did what I always do when I need to think.”

Sarah went out for a long session of rowing, which helped bring clarity to the issue at hand. She had in mind the fact that every child of a parent with HD has a 50-50 chance of inheriting the genetic mutation.

“I came up with a thought: three out of four, we’ve beaten the odds,” she said. “And for the next two weeks, every time I caught myself thinking in a negative way, I ran that thought into my brain. And people would come and go, ‘We’ve heard the news about John (the last to be tested). How do you feel?’ And I’d go: ‘three out of four, we’ve beaten the odds!’

“And it helped, because suddenly I was part of it, and I was with them.”

Sarah struck a similarly optimistic, sometimes even jovial chord throughout her speech. (You can watch an excerpt in the video below.)

 

At dinner, Sarah regaled a group of conference attendees with other stories from her athletic career as well as her mother’s spirited fight against HD. Though HD patients rarely live two decades beyond onset, Val has now lived with the disease for about 25 years.

I felt infected by Sarah’s optimism.

“In all of my years of dealing with HD, you are the most positive individual I have ever met,” I told Sarah as I prepared to retire for the evening.

I hugged her and gave her a brotherly kiss on the forehead. “You are not going to get HD,” I declared. She smiled broadly as she thanked me.

As an HD gene carrier, I live with the stark knowledge of the disease’s inevitability. However, scientists believe that personal enrichment and staying active and positive might very well help delay onset. And there is the very real hope of an effective treatment for Sarah, me, and the entire HD community.

Sarah Winckless and Gene Veritas (photo by Simon Noble, CHDI)

That night and into the next day, I thought of how I need to maintain my own positive attitude – not just to bolster myself in the fight against HD, but to become a better husband, father, coworker, and citizen.

As the HD therapeutics conference proceeded, Sarah’s spirit lived on as the participants presented new research demonstrating a deeper understanding of HD and continued progress in the quest for treatments.

We all need to become infected with Sarah’s optimism.

Like the Winckless family, we must all bond together in this fight.

As difficult and terrible as it may feel, we are never alone.

“Three out of four, we’ve beaten the odds” – despite her own adversity, Sarah found joy in her siblings’ good fortune.

She has reminded us of a key lesson: no matter how difficult our situation, our lives mean so much more than the fight against HD.

Next time: a report on the therapeutics conference.