Brain donation programs – now perhaps at risk of losing funding – are key to a Huntington's disease cure: a family's story

 

In July 2022 Dorlue Schulte of San Diego died at home after a long struggle with Huntington’s disease. To benefit HD research, Dorlue donated her brain to the Harvard Brain Tissue Resource Center (HBTRC) at the nonprofit McLean Hospital in suburban Boston.

 

“They can get hundreds of samples from one donation, so it’s truly the gift that keeps on giving,” said Dorlue’s husband and main caregiver Doug in a presentation last October at the Huntington’s Disease Society of America (HDSA) San Diego chapter’s “Family is Everything” Education Day.

Doug observed that HD researchers are “coming up with great ways to inspect the brain to learn from them.”

 

Dorlue Schulte (family photo)

 

“Scientists now have the ability to look at every cell in the brain and look at the mRNA and the proteins in the cells to see if they are resistant or not resistant to Huntington’s disease and, more importantly, probably, the timing of when (cell) death occurs,” Doug explained. “They’ve got to compare it with a brain that’s not diseased.”

 

For his outstanding advocacy Doug received the 2021 Woody Guthrie Award at the HDSA national convention. He served on the HDSA-San Diego board from 2019-2022. A retired firefighter, Doug has raised awareness about HD among police officers to make them “a friend, not a foe,” when encountering affected individuals.

 

You can watch Doug’s 30-minute talk in the video below.

 

 

‘Precious’ human data

 

Besides research on HD mice and many other non-human species, study of HD brains provides “precious” human data in the quest for treatments, in the words of Robert Pacifici, Ph.D., the chief scientific officer of the key, HD-focused CHDI Foundation, Inc.

 

At meetings like CHDI’s Annual HD Therapeutic Conference scientists discuss the growing body of knowledge coming from these brains.

 

Doug was inspired to present Dorlue’s story in part by Dr. Pacifici’s statements about the importance of research in humans. Although the huntingtin gene exists in many species, only humans develop HD.

 

Over 10,000 brains collected

 

Founded in 1978 and one of the first brain banks in the U.S., Harvard Brain Tissue Resource Center is one of six repositories that are part of the federal National Institutes of Health (NIH) NeuroBioBank, a centralized resource for the collection and distribution of human brain specimens for research.

  

According to the HBTRC website, it has collected over 10,000 brain donations from across the U.S. and distributed over a hundred thousand samples, both nationally and globally, that have resulted in hundreds of publications. More than 45 different brain disorders are represented in the HBTRC collection, including HD.

 

HDSA endorses HBTRC. The two have a long-standing collaboration, and HBTRC has one of the largest collections of brains donated by persons diagnosed with HD in the U.S. if not the world.

 

The HBTRC’s home, McLean Hospital, is the largest psychiatric teaching hospital of Harvard Medical School.

 

The sole funder of the HBTRC is the federal NIH, HBTRC director Sabina Berretta, M.D., wrote in an e-mail interview with me on July 25. An associate professor of psychiatry at Harvard Medical School, she carries out HD research on the team of investigator Steve McCarroll, Ph.D., whose lab has created precise techniques for measuring the impact of HD on single brain cells.

 

As Doug pointed out, this type of research is only possible because of brain donations.

 

The uncertainty of future public funding

 

Harvard University has sued the federal government to try to block the Trump administration’s freezing of nearly $3 billion in research funds. The government also seeks to eliminate $783 million in NIH funding.

 

A statement on the NeuroBioBank website reads: “This repository is under review for potential modification in compliance with Administration directives.”

 

Responding to my questions about this situation, Dr. Berretta wrote that the cuts at Harvard and the NIH have not currently impacted the HBTRC. The government has not flagged current funds, she added. She noted, however, that “we are not sure at the moment” about potential restrictions arising from government concerns about diversity, equity, and inclusion. 

 

Dr. Berretta explained that the HBTRC NIH contract “will end in October 2025. It is not known at this time whether and how the new contract, expected to start in November 2025, will be impacted.”

 

Dr. Berretta explained that “the current funding uncertainty creates some challenges, particularly for talent retention and long-term planning, both critical to our work.”

 

“The other 5 brain banks part of the NIH NeuroBioBank are in our same situation,” she added.

 

Dr. Sabina Berretta (McLean Hospital photo)

 

A family discussion and a decision

 

Dorlue was 63 and had been married to Doug for 32 years. After graduating from high school in 1976, she worked for 20 years in a Pacific Bell office. She volunteered at her church, participated in her son Ryan’s school PTA, and enjoyed family camping trips. As a young adult, Ryan tested negative for the HD gene.

 

Dorlue was remembered as having “a fighting spirit that never wavered in the face of her diagnosis” with HD, including participation in clinical trials in hopes of a cure.

 

Doug and Dorlue discussed, and then agreed to, donating her brain when she was no longer in “denial” about her disease and learning that Ryan was now free of the disease, Doug said in his presentation. Dorlue registered for the donation in 2012.

 

“It should be your decision and no one else’s,” Doug emphasized, noting that contemplating a donation can be “very stressful” because of all of the difficulties already involved in HD.

 

The decision must involve the person’s legal first of kin, who will see through the donation after the person has died.

 

There are many reasons to donate – or not donate, said Doug, noting that some might have religious reasons against the process.

 

He recommended that families start conversations about donations “early.”

 

“You can cancel at any time,” he said of the process. The opportunity to donate is “a blessing,” he added.

 

A ‘very professional’ organization

 

A person can pre-register their donation on the HBTRC website or register any time over the phone, even after an individual has died, Doug explained.

 

Doug spoke several times with Dr. Berretta.

 

“She’s very compassionate,” he said. “The organization is very professional. I really felt that they understood how difficult it was to go through that process, especially right after your loved one died.”

 

Doug noted several exclusionary criteria that might prevent a brain from being accepted, such as a delay of more than 24 hours in getting the brain to the bank; a stroke or penetrating head injury; or testing positive for HIV, hepatitis B, or hepatitis C.

 

Although “it costs a lot of money for the brain to be put on a plane and sent to Harvard,” the only charges covered by the family are the usual funeral costs, such as cremation or embalming, Doug said.

 

Just 24 hours to get the brain delivered

 

The 24-hour clock for the donation to be received starts at the moment the last person saw the deceased alive, Doug continued.

 

Dorlue died at 6 a.m., when a hospice nurse declared her dead. Doug contacted the funeral home, which needed to transport the body to the facility that “harvests” the brain. The funeral home worker took four hours to arrive, Doug said.

 

“We were ten hours into this before they even took the body out of the house,” he recalled. “I was pretty anxious that we get this thing off.”

 

The brain is packed in ice for transport and placed in the luggage area of the plane so that it stays cold throughout the flight, Doug explained.

Once it arrives at the HBTRC laboratories, the brain is immediately dissected. Part of it is immediately frozen and kept at minus 80 degrees centrigrade. Another part is immersed in formalin. It is then assessed by a neuropathologist, who generates a neuropathology report. Both preparations are made available to investigators.

 

Once the brain arrived at Harvard, Doug received a call reassuring him that it had arrived undisturbed and on time. To preserve the integrity of the tissue for research, the brain is ultimately frozen at minus 80 degrees centigrade.

 

Doug also sent the HBTRC Dorlue’s medical records to assist in their research on her brain.

 

“That’s a big part of what the scientists look at,” he said. “They compare the brain with the symptoms and see if there’s any similarities or not.”

 

Crucial work towards a cure

 

The HBTRC website has an FAQ, donation forms, and phone numbers for making a donation.

 

This HBTRC does crucial work in the quest for a cure.

 

Doug has signed up to donate his brain. I will do the same.

 

As Doug put it, the bank collects brains from around the U.S. and sends samples around the world.

 

“Who knows who’s going to find a cure,” he said.

Savoring 20 years of my Huntington’s disease blog

 

This month I am celebrating the 20 years of this blog.

 

I began At Risk for Huntington’s Disease on January 10, 2005, wanting to “squeeze as much life into my days as possible” before experiencing the debilitating HD symptoms that led to my mother’s death a year later. Because I lived in what I called the “terrible and lonely HD closet” – fearful of genetic discrimination – I used the pseudonym “Gene Veritas,” “the truth in my genes.” That name reflected the fact that I had tested positive for the HD gene in 1999.

 

My mother died at 68, after two decades of debilitating symptoms, which was very painful to watch.

 

I turned 65 last month. By this age, I had expected to have full-blown HD, which would have left me unable to work, drive, or write.

 

But, according to my latest neurological checkup, I don’t yet have apparent HD symptoms!

 

In general, the more abnormal the gene, the earlier the age of disease onset. My mother and I have the same gene mutation, suggesting a similar disease path. However, although my mother’s symptoms started in her late 40s, one or more modifier genes, the functions of which were discovered a decade ago, have perhaps delayed my disease onset.

 

This article is number 336. Each day of good health is a blessing.

 

Gene Veritas (aka Kenneth P. Serbin) with his blog (photo by Regina Serbin)

 

The impact

 

In 2012, I exited the HD closet by publishing an essay – and using my real name, Kenneth P. Serbin – in The Chronicle of Higher Education. It was titled “Racing Against the Genetic Clock.” Going public opened new vistas of advocacy and enabled me to blog with greater transparency.

 

In December 2022. I published a detailed analysis of the blog in “Striving for a Realistic and Unapologetic View of Huntington’s Disease” in the Journal of Huntington’s Disease. It described how the blog has helped give voice to the HD community by exploring the major challenges faced by HD families, becoming a key reference for those families, and chronicling the quest to defeat the disorder.

 

As I observed, the blog has also “helped document the new and harrowing experience of living in the gray zone between a genetic test result and disease onset.”

 

At Risk for HD has addressed multiple topics including advocacy, caregiving, family trauma, coping strategies, genetic testing, discrimination, leaving the HD closet, participation in research and clinical trials, as well as religion, faith, and spirituality.

 

When my mother was diagnosed with HD in 1995 – two years after the discovery of the gene – little hope existed for treatments that could slow the progression of HD. However, in the past decade, advances in academic labs and biopharma firms have led to key clinical trials that show potential for affecting the course of HD and perhaps even a cure (click here to read more).

Telling the story of those complex developments has become a major focus of At Risk for HD. With the growing number of research projects, I have necessarily highlighted those that appear closest to producing actual drugs such as the Roche gene silencing program, which I have covered extensively.

 

In 2021, the first Roche trial showed lack of efficacy. In 2023 Roche started enrolling volunteers in a more focused trial to see if the drug might work at least in some patients. Other key trials are in progress or being planned.

 

Hoping for an HD-free world, savoring life

 

Writing the entries of At Risk for HD has given me great meaning and purpose, which researchers have identified as increasing well-being and positively impacting the course of the disease.

 

For now, I plan to continue blogging as long health permits – and until the quest for a cure is complete.

 

In February, I hope to attend the crucial 20th Annual HD Therapeutics Conference at the Parker Hotel in Palm Springs, CA. The conference is sponsored by CHDI Foundation, Inc., the largest private funder of HD research.

 

In 2011, I delivered the conference keynote speech before 250 scientists, physicians, and biopharma reps – a decisive step towards my complete exit from the closet in 2012 and chronicled in this blog.

 

I have described the conference as the “Super Bowl of HD research,” covered in many blog articles and videos of scientists (see, for example, this one).

 

With the rest of the HD community, I hope for the announcement of effective treatments. I very much look forward to reporting on progress.

 

Just as important is the need to savor life – another key lesson of my journey with the HD community, this blog, and my friends and family.

CRISPR, curing Huntington’s disease, and humanity’s future in Isaacson’s ‘Code Breaker’

In a new book about the broad issue of editing human DNA, a prominent biographer of scientific innovators proposes that such cutting-edge, potentially curative gene editing research prioritize Huntington’s disease.

 

“Our newfound ability to make edits to our genes raises some fascinating questions,” writes historian Walter Isaacson – author of studies of Leonardo da Vinci, Steve Jobs, Albert Einstein, and Benjamin Franklin – at the outset of his recently published The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race.

 

Code Breaker presents a crucial account of the biggest breakthrough in genetics since the discovery of DNA’s structure in 1953 by Francis Crick and James Watson.

 

Editing our DNA, the molecule that makes up our genes and guides our biological lives, to make us less susceptible to microbes like the coronavirus would be a “wonderful boon,” Isaacson suggests in the introduction.

 

“Should we use gene editing to eliminate dreaded disorders, such as Huntington’s, sickle-cell anemia, and cystic fibrosis?” he asks. “That sounds good, too.”

 

Jennifer Doudna, Ph.D., the subject of Code Breaker, has also embraced the concept of gene editing for HD if it can become a safe and effective therapy. Dr. Doudna won the 2020 Nobel Prize in Chemistry for her work in identifying and understanding the natural gene editing process now widely known as CRISPR, and the insight that this tool could potentially be refined for use not only in the laboratory, but ultimately also in the clinic, to alter human DNA.

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Above, author Walter Isaacson learns CRISPR editing, and, below, the cover of Code Breaker (images from Simon & Schuster website).

 

A historic breakthrough, major consequences

 

In Code Breaker, Isaacson traces the influence of the controversial Watson, now 93, on Dr. Doudna and others. He also interviewed Watson.

 

For both general readers and specialists, Code Breaker furnishes an excellent description of Dr. Doudna and others’ investigation of the structure and actions of CRISPR-Cas9, the specific type of gene editing feasible for use in humans.

 

CRISPR stands for “clustered regularly interspaced short palindromic repeats,” a strand of RNA, and Cas-9 for the enzyme associated with the RNA. Cas-9 acts as a type of scissors to cut DNA. The RNA guides the enzyme to the cutting target. There are other types of CRISPR.

 

Ultimately, Isaacson delves into the significance of CRISPR (and related themes such as biohacking and home genetic testing) for the future of humanity. CRISPR can perhaps end single-gene disorders like Huntington’s – but might ultimately also permit us to change such characteristics as IQ, muscle size and strength, and height. Russian President Vladimir Putin has extolled CRISPR as a potential way to produce “super-soldiers,” as Isaacson notes.

 

A powerful bioethical story

 

Isaacson has produced a powerful bioethical study of when and how gene editing should be done. He interviewed Dr. Doudna other scientists on their views. He also consulted bioethicists and their writings.

 

He also contrasts competing political theories regarding editing, pitting the idea of a free-market “genetic supermarket,” where the individual decides, against that of a society (and its government) that would permit editing only if it did not increase inequality.

 

Thus, Code Breaker is a major contribution to bioethics (the ethics of medical and biological research). Isaacson analyzes the potential social, moral, ethical, political, and ultimately biological consequences of gene editing and the conflicts it might produce. Editing the human race could produce many wonders, but also less biological diversity and greater and more permanent inequality, as the rich will almost inevitably gain privileged access to therapies and enhancements.

 

Isaacson illuminates this dilemma by recounting Dr. Doudna’s own “ethical journey” on gene editing.

 

“By limiting gene edits to those that are truly ‘medically necessary,’ she says, we can make it less likely that parents could seek to ‘enhance’ their children, which she feels is morally and socially wrong,” he writes. The lines between the different types of edits can be blurry.

 

“As long as we are correcting genetic mutations by restoring the ‘normal’ version of the gene – not inventing some wholly new enhancement not seen in the average human genome ­ – we’re likely to be on the safe side,” Dr. Doudna affirms.

 

Code Breaker also offers important evidence of the tension between so-called open science, where researchers (and some biohackers) freely share data, and the scientists, universities, and corporations that fight to establish patents and earn profits. (Click here for more on this development.)

 

Making the case for editing the HD mutation

 

Isaacson recounts how, in 2016, Dr. Doudna was especially moved by a visit at her workplace, the University of California, Berkeley, with a man from an HD family, who described to her how his father and grandfather had died of the disease, and that his three sisters, also diagnosed with the disorder, now “faced a slow, agonizing death.”

 

Putting Huntington’s first in a series of bioethical case studies, Isaacson underscores the crucial need for an HD CRISPR treatment, noting the disease’s devastating symptoms and rare, dominant genetic nature (inheriting the mutation from just one parent is sufficient for getting symptoms).

 

“If ever there was a case for editing a human gene, it would be for getting rid of the mutation that produces the cruel and painful killer known as Huntington’s disease,” Isaacson asserts.

 

Eliminating HD forever

 

For HD, Isaacson suggests a germline edit—removing the elongated piece of DNA in the huntingtin gene that causes HD in an embryo. A treatment done at this stage would restore the normal function of the HD gene in all the body cells, including that individual’s eggs or sperm. This genetic repair would then be inheritable, thus erasing HD forever from the future generations of the family.

 

Scientific protocol and governments have not yet approved such edits, though they have been done in animal subjects. As narrated in great detail in Code Breaker, a Chinese researcher did such an edit – to prevent AIDS – in twin babies in 2018, only to be punished by his country’s government and criticized as irresponsible by scientific colleagues. However, Dr. Doudna and other pioneers of CRISPR remain hopeful that safe, inheritable edits will become acceptable for at least some conditions.

 

Isaacson mentions two alternatives to germline editing that can eliminate HD from a family’s lineage. First, adoption. Second, preimplantation genetic diagnosis (PGD), which involves in vitro fertilization using embryos screened for the mutation. PGD has been used in the HD community for about 20 years. Before PGD arrived, some families, like mine, have had our offspring tested in the womb. However, neither of these strategies have been used widely in the HD community by at-risk couples.

 

If it can be harnessed safely, to target only the abnormal HD gene, and delivered effectively to human cells, CRISPR could provide the all-out cure for Huntington’s long sought by science and so deeply hoped for by HD families.

 

Isaacson concludes, “it seems (at least to me) that Huntington’s is a genetic malady that we should eliminate from the human race.”

 

For now, don’t ‘hold your breath’ for an HD CRISPR therapy

 

Isaacson states that “fixing Huntington’s is not a complex edit,” but he does not elaborate further.

 

However, while leading HD scientists are eagerly using CRISPR as a research tool, the technique is far from ready as a therapy.

 

CRISPR was a key topic at the “Ask the Scientist … Anything” panel of the virtual 36th Annual Convention of the Huntington’s Disease Society ofAmerica (HDSA), held June 10-13. Noting that many in the HD community have inquired about CRISPR, HDSA Chief Scientific Officer George Yohrling, Ph.D., asked the panel to comment on its potential as a therapy.

 

“CRISPR is really an exciting tool,” said researcher Jeff Carroll, Ph.D., co-founder of the HDBuzz website and, like me, an HD gene carrier who lost his mother to the disease. “CRISPR allows us really for the first time to edit DNA itself in a very precise way, to make very precise cuts in the DNA of a cell or even in an intact organism.” He added: “scientists are using it like crazy” in lab experiments.

 

In his own HD-focused lab at Western Washington University, Dr. Carroll and his team have developed a line of experimental mice with cells containing enzymes (proteins that act as chemical catalysts) necessary for doing CRISPR edits, Dr. Carroll explained. Such enzymes do not normally occur in human cells, he added.

 

Using CRISPR, “we can mess with these mice’s genome [DNA] in ways that were unimaginable just a few years ago,” Dr. Carroll continued.

 

Dr. Jeff Carroll commenting on HD science at the virtual 2021 HDSA national convention (screenshot by Gene Veritas, aka Kenneth P. Serbin)

 

For an HD family, “the idea of cutting out the DNA and fixing it is very, very appealing and something we can do in animal models and [animal and human] cell lines in the lab already, and it looks really promising.”

 

However, Dr. Carroll offered a blunt assessment of the current state of research on CRISPR as an HD treatment.

 

“As an actual HD therapy, I’m less excited about CRISPR,” he said. “I think it’s many years away. Something based on it may someday help us, but you have to realize that these enzymes that you need to enact CRISPR are themselves giant proteins that actually originate from bacteria, and we have to put them into the cell.

 

“So, if you want to use CRISPR as a therapy for Huntington’s and we want to modify all the DNA in the whole brain, we have to get into every one of your 84 billion neurons and put a CRISPR factor in there and modify the DNA.”

 

As a result, “Huntington’s will not be the first disease treated with CRISPR,” Dr. Carroll concluded. “I wouldn’t hold your breath for it as a therapy for HD in the medium or short term.”

 

Currently, a possible better candidate for a CRISPR treatment would be a disease involving immune cells that could be removed from the body, edited, and then reintroduced into the individual, Dr. Carroll observed.

 

Elaborating on Dr. Carroll’s comments, Ed Wild, M.D., Ph.D., another speaker at the HDSA science panel and also a co-founder of HDBuzz, cited the example of a blood cancer as a possible early target for CRISPR.

 

He agreed with Dr. Carroll that an HD CRISPR treatment remains difficult at this time and underscored why: unlike parts of the body like blood cells or bone marrow, brain cells cannot be removed, treated, and reinserted or given replacements.

 

Further cautions

 

An August 2020 HDBuzz article also urged caution in the use of CRISPR for HD and other genetic diseases in the wake of three experiments with human embryos that resulted in “unintended changes in the genome.” These so-called “off-target” effects suggest that “CRISPR is less precise than previously thought,” the article stated. Like desired edits, the unwanted ones make permanent changes to the DNA.

 

Such unintended edits are “bad because our DNA code is a very precise set of instructions, which can be thought of like a cooking recipe,” the article explained. “If you rearranged the steps in a recipe or got rid of some of the ingredients the outcome would not be good!”

 

When CRISPR is used in an embryo, the mistaken edits would not only affect that individual, but could also be passed on to the next generation.

 

Clarifying some key points

 

As an HD advocate and family member who has tracked the research for two decades, I felt that Code Breaker could have gone into greater depth about HD science. Given all the valuable detail about Dr. Doudna’s and other scientists’ efforts to discover the workings of CRISPR, it would have been helpful to present some scenarios about how it might work in HD.

 

Code Breaker also states that in HD the “wild sequence of excess DNA serves no good purpose.” This is a confusing term, as so-called “wild” type DNA in this context usually means “normal” DNA. Isaacson might better have done better to avoid the use of this term, but instead to emphasize that the normal huntingtin gene is essential for life and brain cell stability, as HD research has demonstrated. Normal huntingtin is present in all humans without the mutation and even in those who have inherited a mutation from one parent, because the non-HD parent has passed on a normal copy of the gene.

 

The book could have further benefited from additional references to both the scientific and social significance of the disease as presented in works such as Dr. Thomas Bird’s Can You Help Me? Inside the Turbulent World of Huntington Disease. There was also no reference to the pathbreaking research on modifier genes, which can hasten or delay the onset of HD.

 

Contemplating the ‘gift’ of life

 

Citing the philosopher Michael Sandel, Isaacson points out that finding “ways to rig the natural lottery” of genetics could lead humanity to humbly appreciate the “gifted character of human powers and achievements. […] Our talents and powers are not wholly our own doing.”

 

Still, I agree with Isaacson that “few of us would regard Alzheimer’s or Huntington’s to be a result of giftedness.”

 

Even so, it’s important to recall that HD researchers continue to investigate the role of the huntingtin gene not only in the disease, but, in the words of one study, in intelligence and the “evolution of a superior human brain.”

 

Faced with the daunting challenges of the disease, many HD mutation carriers and affected individuals have also grown in unexpected ways. I, for one, consider myself a lucky man because of the richer life I have lived as a result of my family’s fight against Huntington’s.

 

In this new reality, advocating once again for our families

 

HD families like mine have lived on the frontier of bioethics, facing challenges such as genetic testing, prenatal testing, genetic discrimination, decisions on family planning, and many others.

 

Perhaps, as Code Breaker speculates, gene editing may someday be considered morally acceptable in the way that in vitro fertilization and PGD have come to be.

 

However, as seen in the case of abortion, the HD community does not have a monolithic bioethical stance (click here and here to read more).

 

It remains an open question as to whether the HD community would wholeheartedly embrace CRISPR as a therapy. Some might celebrate it as a cure, but others might see it as going against nature or even as a return to the era of eugenics in the early- to mid-20th century, when medical professionals advocated sterilization for HD-affected individuals. Taking a cue from the United States, the Nazis were said to have forcibly sterilized as many as 3,500 people affected by Huntington’s.

 

No book can offer a definitive answer to these ethical quandaries. Code Breaker provides us with at least some basic guideposts.

 

It will ultimately fall to HD-affected individuals and their families (and those families affected by other diseases) to navigate what could very soon become the new reality of gene editing – and, when necessary, to act as powerful advocates. To assist us in this journey, we will need ethically informed health professionals and patient organizations.

An ‘electric,’ inspiring Thanksgiving for the Huntington’s disease community

Thanksgiving is my favorite holiday. I’ve reflected on it many times in this blog. For me, rather than the commercialism and stress associated with the holidays, it’s truly a day of relaxation, the warmth of friends and family, and gratitude.

This year, the Huntington’s disease community has bountiful reasons for thanks. Several clinical trials to test what might become the first effective treatments are in progress, and the community has demonstrated spirited participation.

The historic Roche gene-silencing program successfully started its crucial third and final phase, GENERATION HD1, earlier this year. The program includes an open-label extension of all 46 participants in the first phase, completed in December 2017, all of them receiving the drug RG6042 via a monthly injection into the cerebrospinal fluid (CSF).

“Two years ago, we showed for the first time – about 25 years after the discovery of the gene –the ability to lower CSF levels of mutant huntingtin [protein] in patients with HD, which was a very exciting first-in-human accomplishment, and that was really the springboard that allowed us to proceed to our global development program,” Scott Schobel, M.D., M.S., Roche’s associate group medical director and clinical science leader for RG6042, reported at the 26th annual Huntington Study Group (HSG) meeting on November 8. “So these heroic 46 volunteers were the foundation of that.”

GENERATION HD1 is “recruiting incredibly well,” Dr. Schobel said. “It’s been absolutely electric.” Total worldwide enrollment in GENERATION HD1 and related studies has surpassed 800. “It’s been a huge response from the community,” he added.

Several other programs provided updates at the HSG meeting.

Although much work remains to develop effective therapies, HD families and their supporters can feel proud for helping further the progress achieved in 2019.

Priscilla’s inspiring fight and peaceful paintings

An HD-stricken woman I know from Brazil, Priscilla Ferraz Fontes Santos, embodies the life-force of the HD cause. I saw Priscilla in 2013 at the sixth World Congress on Huntington’s Disease in Rio de Janeiro, and got to know her at #HDdennomore, Pope Francis’ special audience with the HD community in Rome in 2017.

Brazilians don’t celebrate Thanksgiving, but Priscilla’s words, paintings, and photos help us feel the peace and hope of our quintessentially American holiday.

Priscilla was stricken with juvenile HD as a teenager. She had played soccer, pursued acting, and completed her journalism degree, but the disease prevented her from finishing a second degree in tourism.

Many juvenile patients do not live past 30. Priscilla is 36. She takes no drugs to control her involuntary movements and other symptoms but instead relies on alternative and spiritual approaches, including yoga. However, she also follows HD clinical trials and hopes for a cure.

Starting November 22 and ending December 10, Priscilla and her art teacher are staging an exhibit of Priscilla’s paintings in Serra Grande, a town in the state of Bahia. They have called it “Colored Atmosphere.”

Priscilla with two of her paintings (family photo)

“The past two and a half years, I have been taking painting and art classes, and I have discovered for myself the pleasure and well-being that painting brings,” Priscilla wrote in an introduction to the exhibit. “As I await the cure, I have gained the courage to overcome many difficulties and meet challenges with the ever-present support of my family, friends, and health professionals who care for me.”

Priscilla ended with this wish: “I hope that you enjoy my paintings and that they awaken in you all of the strength, beauty, and joy with which I painted them.” (I translated the text from the original Portuguese.)

Priscilla is an “inspiration of strength and positive thinking” for all of us, Priscilla’s mother Lígia wrote in a message in Brazilian WhatsApp group dedicated to the HD cause.

Priscilla practicing yoga (family photo)

Symptom-free, but awaiting treatments

As always, I am profoundly grateful for not having yet developed any of the inevitable classic symptoms of HD, which struck my mother in her late 40s and ended her life at 68.

I turn 60 next month – an age at which my mother had full-blown HD and could no longer care for herself.

Last week, I presented my new book on Brazilian history to an audience at the University of San Diego. I had never imagined I would still be able to write at age 60.

Even more importantly, I’m able to continue supporting and loving my wife Regina and daughter Bianca. A sophomore at the University of Pennsylvania and HD-free, Bianca will spend Thanksgiving with friends in Connecticut. However, in a few weeks she will be home for winter break.

I am crossing my fingers that GENERATION HD1 and other trials can produce an effective treatment – and that I can hold on long enough to benefit and share more precious time with my family.