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.

At Therapeutics Conference, landmark study of young gene carriers highlights how Huntington’s disease researchers seek to solve critical puzzles

Armed with ever more impressive data and a deeper understanding of Huntington’s disease, scientists and drug hunters convened at the 15th Annual HD Therapeutics Conference this week, facing the complex puzzles that still hinder the quest for treatments for this deadly neurological disorder.

One of those puzzles: how to not only treat symptoms, but to prevent them, especially in young presymptomatic carriers of the HD gene, so that they don’t have to spend their lives fearing the currently inevitable onset of this devastating disease.

On February 26, Sarah Tabrizi, FRCP, Ph.D., of University College London, answered key questions about what kinds of health consequences young presymptomatic gene carriers suffer decades before they’re likely to develop the disease in midlife.

Previous studies have demonstrated that brain shrinkage can occur as early as 15 to 18 years before predicted age of onset. Ranging in age from 18-40, the 64 gene carriers in Dr. Tabrizi’s HD Young Adult Study went through state-of-the art brain scans and cognitive testing, and also provided samples of blood and cerebrospinal fluid (CSF) for analysis. These at-risk volunteers are, on average, 24 years from estimated onset.

This study, in line with “The Path to Prevention” (one of five major themes of the 2020 conference), is aimed at helping identify the optimal time to treat gene carriers to slow or prevent their neurological decline.

“Comprehensive cognitive testing was normal,” as compared to 67 non-HD-affected individuals, reported Dr. Tabrizi in her presentation to the conference. “There were no significant psychiatric differences, which I found very interesting, because I would have predicted they would’ve been big differences.”

Dr. Tabrizi said that "there’s always been a thought that carrying the HD gene hard-wired you for psychiatric burden,” but the Young Adult Study suggests that such symptoms become more prominent closer to onset.

“I think that was – and I don’t say this lightly – a landmark presentation,” Robert Pacifici, Ph.D., the chief scientific officer for CHDI Foundation, Inc., the conference sponsor, told me today, adding that Dr. Tabrizi’s team carried out the study with “a high degree of rigor and granularity.”

“The participants seem to be remarkably well,” Dr. Pacifici observed. The absence of many of the neurological and other problems typical of HD is an encouraging prospect for developing safe and well-tolerated treatments that could “not just reverse, but actually prevent” HD, he said.

Dr. Pacifici lauded the study volunteers for their "unbelievably selfless participation," including submitting to the study's "incredibly rigorous battery."

Above, Dr. Sarah Tabrizi presenting her talk on the HD Young Adult Study at the 2020 HD Therapeutics Conference, February 26, 2020, and, below, a closeup of Dr. Tabrizi (photos by Gene Veritas, aka Kenneth P. Serbin)

Overall, ‘good news’ for young gene carriers

The young gene carriers in the study did appear to go through a small change in the area of the forebrain known as the striatum, consisting primarily of the putamen and the caudate, the deep brain regions that are most affected by HD. The striatum helps to control our movements and rewards system.

The study found a significant reduction in the size of the putamen, but an insignificant reduction in the caudate. Nevertheless, Dr. Tabrizi explained that, based on this study, these differences (in comparison with the normal subjects) were “not associated with predicted years to onset.”

“So what we now know, based on the data, is that the striatum never appears to be the same size as the control group,” she explained. 

The “very slightly smaller” striatum may suggest a “neurodevelopmental effect” (the way the brain develops) that is “well compensated for,” Dr. Tabrizi said, meaning that the brain adjusts without clear damage. She added that it “might be why the striatum is vulnerable later in life, because it has a double hit.” As mentioned by Dr. Tabrizi, this interpretation resonates with the research of Peg Nopoulos, M.D., who has studied the compromised development of the brains of people affected by juvenile HD.

Alternatively, neurodegeneration early on could be “too subtle and variable” to associate with predicated age of onset, Dr. Tabrizi noted.

Other imaging results showed no decrease in the white matter (the tissue in the brain made of nerve fibers and possibly involved in cognitive problems in HD) or any other aspect of the brain measured in the study, indicating that the subjects were still “very far from onset,” Dr. Tabrizi continued.

“This is really good news,” Dr. Tabrizi stated.

Douglas Langbehn, M.D., Ph.D., a psychiatrist and biostatistician at the University of Iowa who did the statistical analysis for the HD Young Adult Study, listens to Dr. Tabrizi at the Therapeutics Conference (photo by Gene Veritas).

The ongoing search for reliable biomarkers

The study also involved the ongoing search for reliable biomarkers (signs of disease and drug efficacy).

The study detected mutant huntingtin protein in the subjects’ cerebrospinal fluid. “CSF mutant huntingtin was higher in those closer to [predicted] onset, suggesting that some injury is releasing mutant huntingtin [from the brain], but very subtle,” Dr. Tabrizi said.

Several other biomarkers were elevated in the subjects’ CSF, again indicating an early, subtle injury, but most of those subjects had readings showing levels very close to those of the unaffected control subjects, Dr. Tabrizi continued. Furthermore, six other biomarkers were normal, she added.

The Young Adult Study points to the one CSF biomarker in particular, neurofilament light, a marker of brain damage, as potentially helpful in measuring disease progression and treatment response in people decades from onset, Dr. Tabrizi concluded.

A drug that kept neurofilament light at very low levels could prevent degeneration of the brain, she added.

You can watch Dr. Tabrizi’s presentation in the video below.

A moving keynote address

With a record attendance of 380, the conference opened on February 24 with a moving keynote speech by Amy Merkel, a 45-year-old nurse from Wisconsin and the founder of Starfish Yoga.

A small company, Starfish focuses on encouraging constructive coping skills, primarily for people affected by past imprisonment, sexual abuse, and neurological disorders, including HD.

Amy, who titled her talk “Life is Good,” belongs to a family deeply affected by HD. She recounted her extended family’s decades-long struggles with HD. Amy received a standing ovation.

Stay tuned to this blog for additional reporting on the conference, including an overview provided in my interview with Dr. Pacifici.

Above, HD advocate Amy Merkel addresses the 15th Annual Therapeutics Conference, and, below, poses with researchers Dr. Sarah Tabrizi (far left), Leslie Thompson, Ph.D. (second from right), and Gillian Bates, Ph.D. (photos by Gene Veritas).

‘Navigating’ the Huntington’s disease community towards crucial clinical trials

As scientists and drug companies expand the array of potential treatments for Huntington’s disease, the Huntington Study Group (HSG), the world’s largest HD clinical research network, is redoubling its efforts to educate the HD community for current and upcoming clinical trials and train the necessary medical personnel.

A record 700-plus participants focused on these themes at the 26th annual HSG Meeting, titled “HSG 2019: Navigating HD,” November 7-9 at the Hyatt Regency hotel in Sacramento, CA. (Attendance at the HSG 2017 and 2018 meetings was over 600.)

Clinical trials are crucial for demonstrating drug safety and efficacy. The number of HD trials has increased in recent years, bringing hope for better treatment of the devastating symptoms and perhaps even an attack on the root causes. Key trials in progress include GENERATION HD1, run by Roche, and SIGNAL, administered by the HSG and Vaccinex.

“Figuring out how these trials are going to work, what they’re aiming to do, and what an individual patient or family should do to get involved or not get involved has become complicated, to some extent,” Andrew Feigin, M.D., the HSG chair and a professor of neurology at New York University Langone Health, told me in a November 6 interview. “That’s my interpretation of the ‘navigating HD.’ We’re trying to get at some of these novel therapies and clarify where they’re headed, where they stand, how the HSG can get more involved, and figuring out where people can go for the cutting-edge therapies for Huntington’s disease.”

In the conference-opening “HSG State of the Union” presentation by HSG leaders and staff, executive director Shari Kinel, J.D., reported that the event involved 15 countries, 23 companies, 9 advocacy groups, 17 sponsors, and 15 exhibitors. The sponsors included Roche’s American subsidiary Genentech and Vaccinex.

“This incredible showing […] is a sign that the HSG has more partners, more colleagues, more friends than ever who are engaged, dedicated, and committed to seeking treatments that make a difference for those impacted by Huntington’s disease,” Kinel told the audience.

Dr. Feigin affirmed that in the past year, the HSG has doubled its paid staff from four to eight, plus one part-timer, although he declined to reveal the organization’s annual budget. Headquartered in Rochester, NY, the HSG is mainly funded by firms like Vaccinex that it partners with on clinical trials, he explained. Sponsors cover the cost of the annual meeting.

The audience watches a presentation by Dr. Arthur Combs at the "HD Innovators Forum" at the 26th annual HSG Meeting (photo by Gene Veritas, aka Kenneth P. Serbin)

A full-service organization

The HSG was founded in 1993, the year of the discovery of the huntingtin gene. Dr. Feigin described the nonprofit organization as a “full-service” contract research organization that can carry out all aspects of an HD clinical trial.

In her speech, Kinel stated that the HSG member network includes 801 investigators (researchers), trial coordinators, scientists, and HD experts. Around the globe, the organization has credentialed 127 sites for HD trials, and HSG members have worked with more than 21,000 HD-affected individuals, she said.

The HSG also developed the Unified Huntington’s Disease Rating Scale (UHDRS), the primary assessment tool in HD clinical trials. It consists of tests of a person’s movements, cognition, behavior, independence, and functional capacity.

The “HSG State of the Union” presentation outlined the HSG’s mission, accomplishments, clinical trials, educational activities, efforts to improve patient care, and plans for the future.

You can watch the presentation in the video below. Click here for my video album of the event, which included a variety of presentations on patient care, clinical trial techniques and measurements, new scientific findings, and innovations in drug and clinical trial development.

Seeking a better drug to treat chorea

Prior to the main conference, the HSG held organizational meetings for KINECT-HD, a Phase 3 clinical trial by the HSG and San Diego-based drug developer Neurocrine Biosciences to test the efficacy of valbenazine to treat chorea, the involuntary movements typical in HD. 

The HSG ran the successful clinical trials of two other drugs for chorea, Xenazine and Austedo, the only HD-specific medicines to receive approval from the U.S. Food and Drug Administration (FDA). On November 14, it issued a press release announcing the start of the 18-week trial, which seeks to enroll HD-affected individuals with chorea at 55 sites in the U.S. and Canada.

In 2017, valbenazine was approved by the FDA with the name Ingrezza for the treatment of tardive dyskinesia, an irreversible involuntary movement disorder. This status allowed Neurocrine and the HSG to take it directly into a Phase 3 trial for HD.

Like Xenazine and Austedo, valbenazine is a VMAT2 inhibitor. Xenazine requires three daily doses, and Austedo two. 

“The upside thing of valbenazine is that it’s a drug that can be dosed once daily,” said Dietrich Haubenberger, M.D., the Neurocrine medical director, in a presentation forming part of the “HD Research Round-Up” at the close of the scientific sessions on November 8.

Wearable sensors and the search for biomarkers

In the quest for HD treatments, researchers hunt for new biomarkers, that is, signs of the disease and the effect of remedies. Biomarkers are especially critical in brain-related diseases, because doctors cannot do biopsies on the organ.

With a key innovation, KINECT-HD will also look for biomarkers. It will be the HSG’s first trial in which participants use wearable sensors – for continuous monitoring of their movements and other biological functions, even at home. Researchers hope this more detailed monitoring will provide both a better understanding of chorea and valbenazine’s impact on it.

Called BioStamp nPoint, the sensors were designed by MC10, Inc., and cleared for use by the FDA. MC10 is based in Lexington, MA.

MC10 chief medical officer Arthur Combs, M.D., described the system at the conference’s “HD Innovators Forum.”

“It weighs less than eight grams [0.28 oz.],” Dr. Combs said, explaining that the sensor can be placed anywhere on the body and worn even during showers and swimming. “It’s like putting on a Band-Aid.”

MC10 developed 44 algorithms for the system to help measure trial participants’ data. In addition to chorea, BioStamp nPoint will help investigators observe individuals’ gait, heart rate, sleep, posture, and other bodily functions, Dr. Combs added.

In one previous study, “patients with symptomatic Huntington’s disease spent 50 percent of their day” lying down, he explained. That may be a response to exhaustion or the risk of falling, he said. Thus, the BioStamp nPoint system could help determine whether lying down is a “marker” for the disease, and whether less time at rest is a sign of drug efficacy, he said. It also accounts for the uniqueness of each patients, he added.

To obtain continuous data in GENERATION HD1, Roche developed an HD Digital Monitoring Platform, with participants wearing a smartwatch and using a smartphone.

You can watch Dr. Combs’ presentation in the video below.

The latest clinical trial news

In addition to Neurocrine, other firms reported on their clinical trials during the “HD Research Round-Up”: Voyager Therapeutics, uniQure, Wave Life Sciences, Vaccinex, and Roche.

The Roche GENERATION HD1 update of the company’s historic Phase 3 clinical trial of the drug RG6042 was one of the most anticipated. A gene-silencing drug, RG6042 is aimed at the roots of HD and caused a stunning improvement in the health of HD-affected mice. On October 14, Roche announced that it was expanding the number of trial participants from 660 to 801 and adding China to the nearly 20 countries in the study.

The announcement noted that recruitment in the U.S. had “exceeded expectations” and was now complete. Expanding the number of volunteers and adding China will allow for more abundant data and the study of a more diverse population, Roche said.

Enrollment for the Roche HD program has been “absolutely electric,” with over 800 individuals already in 2019 in GENERATION HD1 and related HD studies, said Scott Schobel, M.D., M.S., Roche’s associate group medical director and clinical science leader for RG6042 (click here to watch Dr. Schobel’s presentation). If the trial is successful, Roche will apply for drug approval from the FDA and regulatory agencies in other countries.

On November 9, HSG held a “Family Day” for the HD community, with presentations by advocates like me, presentations by scientists, and an update on GENERATION HD1.

In upcoming articles, I will report on Family Day and more of the scientific and clinical developments discussed at the meeting.

Disclosure: my travel expenses were covered by the HSG and the Department of History of the University of San Diego.

CHDI's 13th conference promises some good news for the Huntington's disease community

With potential Huntington’s disease treatments on the horizon, I am looking forward to the 13th Annual HD Therapeutics Conference with great anticipation.

Although a powerful reminder of my gene-carrier status, the opportunity to watch world-class academic and pharmaceutical researchers present their latest findings always leaves me with increased hope that I won’t die from HD like my mother.

Sponsored by CHDI Foundation, Inc., the conference takes place at the Parker Palm Springs hotel in Palm Springs, CA, February 26-March 1. It will be my seventh, including an appearance as the keynote speaker in 2011.

The conference will assess progress towards HD treatments and point to future paths for research and clinical trials.

Gene Veritas (aka Kenneth P. Serbin) before the CHDI logo in 2012 (photo by Lev Blumenstein)

A report on the Ionis trial

I’m especially eager to learn about the latest data from the highly successful Ionis Pharmaceuticals Phase 1/2a gene-silencing clinical trial, aimed at reducing the amount of harmful huntingtin protein in brain cells. The project received an initial infusion of about $10 million from CHDI, later repaid by Ionis.

With the end of Phase 1/2a last December, Ionis officials commented only briefly on the demonstrated safety and tolerability of its gene-silencing drug IONIS-HTT_Rx, reserving a more thorough update for scientific meetings.

In the final talk – perhaps saving the best for last – IONIS-HTT_Rx trial administrators Anne Smith, Ph.D. (Ionis) and Sarah Tabrizi, FRCP, Ph.D. (University College of London) will present “Development of IONIS-HTT_Rx: From first principles to the first successful HTT-lowering drug trial.”

I’m hoping that Drs. Smith and Tabrizi will elaborate on the brief report from Ionis scientists in December that the drug did indeed safely and substantially lower the amount of mutant huntingtin protein, as measured in trial volunteers’ cerebrospinal fluid. That was only a first step, but an important one.

As a result, the Ionis scientists stated, clinical trial partner Roche, now the license-holder for IONIS-HTT_Rx, could skip the usual Phase 2 of the clinical trial program, going directly to a full-blown Phase 3. Phases 2 and 3 measure a drug’s efficacy. In consultation with the Food and Drug Administration (FDA) (and regulatory agencies in other countries), a drug company can shape the trial program as it sees fit.

I plan to interview Roche officials in Palm Springs, including Thomas Wiese, M.D., the Patient Partnership Director for the firm’s HD program.

‘The more the merrier’

"Wow, this is truly big news and very exciting news for the whole HD community since it tells us that the drug can do what it is designed to do!” HD specialist Jody Corey-Bloom, M.D., Ph.D., commented via e-mail in mid-December regarding the trial. “Now the hard part – can it make HD better?”

Also impressed, Martha A. Nance, M.D. pointed to the need for deeper clinical research: “Will people taking this treatment stabilize clinically, or improve?  And what about the long-term safety?  Will there be any unanticipated problems six months or five years later?  These are the questions that will require additional larger studies to answer, before the drug is understood well enough to use as a treatment in the clinic.”

“The IONIS results are ushering in a new and more hopeful era,” remarked LaVonne Goodman, M.D., the founder of HDDrugWorks.  “With the demonstrated safety (thus far) of the drug, and the urgency of our Huntington’s family needs, it makes a lot of sense to be going next to a Phase 3 trial.  Let’s hope the regulators think so too.”

Dr. Goodman added that the Cambridge, MA-based Wave Life Sciences is also currently enrolling patients in clinical trials of two gene-silencing drugs that, like Ionis’s effort, use strands of artificial DNA known as antisense oligonucleotides (ASOs) to decrease the huntingtin protein.

She reflected on the fact that, the greater the number of clinical trials, the greater the chances of finding effective treatments for this still untreatable condition.

“Competition is good,” Dr. Goodman said. “The more the merrier.”

Wave's unique approach

Just as the Ionis trial has made history, so might the Wave program. Whereas IONIS-HTT_Rx reduces both the mutant and normal huntingtin that all HD patients have, Wave’s ASOs attack just the mutant by targeting two specific genetic variations found in 70 percent of the HD population.

“We’re able to use the Wave technology to selectively lower the mutant huntingtin, while leaving the wild type, or healthy, huntingtin relatively alone,” explained Wave HD researcher Serena Hung, M.D., in a February 7 webinar sponsored by the Huntington’s Disease Society of America (HDSA) (click here to view). “This is a very unique approach, and this is probably the main difference between the Wave approach and other approaches.”

So far, the trial is enrolling participants in Canada and Poland. During the webinar, Dr. Hung indicated that other countries could be included, but did not mention the U.S. (Recruitment information for clinical trials worldwide is available at https://clinicaltrials.gov/).

For years, researchers have studied and debated the benefits and drawbacks of these different approaches. The distinctive IONIS and Wave trials could provide valuable answers.

At the CHDI conference, Wave’s Michael Panzara, M.D., MPH, will give a presentation on the firm’s program immediately before the talk on the Ionis effort.

Landmarks and a lucky year

In his welcome letter to conference participants, CHDI Chief Scientific Officer Robert Pacifici, Ph.D., notes that 2017 marked HDSA’s 50th anniversary.

“This year [2018] also marks the 25th anniversary of the identification of the huntingtin gene, a landmark accomplishment (for biology generally, not just HD) that of course could not have been achieved without the generous participation of HD families who volunteered their family history and donated their DNA.”

Dr. Robert Pacifici (photo by Gene Veritas)

The participation of thousands of HD family members in genetic research and other projects has helped shape CHDI and the HD field’s focus in the quest for treatments. That includes the “exciting new area” of DNA repair and handling, a theme of this year’s conference.

In addition to the popular, ever-expanding conference poster session, this year’s conference will include a resource fair, an innovation introduced at the 2017 conference in Malta. (Every fourth year, the conference is held in Europe.) The fair will display scientific tools and technologies useful in HD research.

“We are delighted to return to our ‘home’ here at the Parker Hotel in Palm Springs for lucky number 13!” Dr. Pacifici quips in his letter.

I officially became an advocate two decades ago this April by joining the board of HDSA-San Diego, where I served for twelve and a half years.

Blessed to have avoided symptoms so far, and observing the vast progress in HD research over these past two decades, I believe that 2018 could indeed be a lucky year for our community.

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