With ‘great promise’ for treating Huntington’s disease, four drug programs press ahead (Part II)

 

At the recent 20th Huntington’s Disease Therapeutics Conference in February, four pharmaceutical companies provided updates on their key clinical trial programs, demonstrating that they had overcome basic safety hurdles and revealing plans to have their drugs potentially approved as therapies (treatments) for delaying the progression of HD symptoms.

 

All four programs use drugs to lower the amount of harmful mutant huntingtin protein in the brain cells of patients.

 

In the first of two articles on these programs, I described the projects of PTC Therapeutics and Roche.

 

In this article, I cover the presentations made by Wave Life Sciences and uniQure.

 

These updates took place during the conference’s first session on February 25, the first day of the three-day event.

 

In a post-conference interview Robert Pacifici, Ph.D., the chief scientific officer for CHDI Foundation, Inc., the conference sponsor, told me that that there is “great promise” regarding these four programs’ potential HD therapies.

 

Attacking only the bad protein, preserving the good one

 

Jane Atkins, Ph.D., Wave’s senior vice president for portfolio strategy and program management, provided an update on the company’s groundbreaking program.

 

Like Roche’s tominersen, Wave’s WVE-003 is an antisense oligonucleotide, an artificial strand of DNA that blocks or lowers the production of the huntingtin protein.

 

However, whereas tominersen and PTC’s votoplam (a splicing modulator) reduce both the mutant and normal huntingtin protein, Wave’s drug is uniquely allele-selective: it attacks just the bad protein and allows the good one to carry out its essential actions unhampered.

 

Clinical trials for drugs usually go through three phases. If the last is successful, the drug can receive approval from the U.S. Food and Drug Administration (FDA).

 

In 2021, in small clinical trials, precursors WVE-120101 and WVE-120102 failed to reduce the bad protein. Wave then developed WVE-003, which entered a clinical trial that same year.

 

At the conference, Dr. Atkins reported that in June 2024 the Phase 1b/2a SELECT-HD study of WVE-003 produced positive results, “including the first allele-selective silencing in any disease.”

 

“A growing body of literature” supports the importance of the good huntingtin protein, she explained, as it sustains the health of brain cells.

 

Slowing the shrinking of the brain

 

In the clinical trial, the bad protein was reduced as much as 46 percent in some volunteers, exceeding the overall goal of 30 percent, Dr. Atkins said, noting that the drug was safe and well-tolerated.

 

Significantly, the study also demonstrated a slowing in the atrophy (shrinking) of the caudate, a key part of the brain dramatically affected in HD, leading to a decline in cognition, function, and movement, Dr. Atkins said. Such atrophy occurs before symptoms appear, she noted, so being able to observe this change early makes the atrophy a good measure of a drug’s effectiveness.

 

The slower shrinking “was the first time this was shown in the clinic,” Dr. Atkins said. “We were super-excited to see this.”

 

With these promising results, Wave plans to put WVE-003 into a combined Phase 2/3 clinical trial, Dr. Atkins said. The company later this year expects to seek FDA approval of the trial. Wave proposes to use caudate atrophy as a primary endpoint, that is, a main measure of WVE-003’s effectiveness.

 

Wave is also investigating WVE-003’s potential impact on somatic expansion, Dr. Atkins said. Somatic expansion is the tendency of the mutant huntingtin gene to continue expanding over time. Many scientists now believe that this process triggers HD symptoms.

 

Somatic expansion is understood as a two-step process where expansion of the gene (step 1) triggers disease (step 2) that drives HD. Wave believes that lowering the bad protein selectively (with WVE-003) is likely to address the second step.

 

As with tominersen, WVE-003 is administered via a spinal tap. Votoplam is a pill.

 

 

Dr. Jane Atkins of Wave Life Sciences displays a slide demonstrating the slowing of caudate atrophy in the WVE-003 clinical trial (photo by Gene Veritas, aka Kenneth P. Serbin).

 

uniQure drug slows disease progression in trial

 

David Margolin, M.D., Ph.D., uniQure’s vice president for clinical development, gave a presentation on the latest developments regarding AMT-130, the firm’s gene therapy drug that reduces the levels of both the good and bad huntingtin protein.

 

In the uniQure clinical trial, a neurosurgeon injects AMT-130 directly into the brains of the volunteers under the guidance of an MRI. As a gene therapy, AMT-130 requires just this one application. (Watch the uniQure video about how AMT-130 is administered here).

 

This small, long-term uniQure Phase 1/2 trial began in 2020. As of April, the number of participants had reached 45, including people from the U.S. and Europe.

 

An interim analysis in mid-2024 showed that “AMT-130 high dose … strongly and significantly reduced disease progression,” Dr. Margolin pointed out. Another analysis found “substantial reduction in risk of clinically meaningful worsening,” he added.

 

As patients continue to go through the trial and beyond, with follow-up, “with every data cut we see… a promising treatment effect becoming more and more evident,” Dr. Margolin said.

 

 

Dr. David Margolin of uniQure presents data illustrating the slowing of HD disease progression in the AMT-130 clinical trial (photo by Gene Veritas).

 

Hoping to accelerate approval

 

The positive results have led uniQure to seek acceleration of FDA approval for AMT-130.

 

Because of HD’s status as a rare disease, in 2017 uniQure received the financially beneficial orphan drug designation from the FDA for AMT-130. In 2019, FDA granted AMT-130 fast track status to further facilitate development of the drug and expedite review.

 

As explained by Dr. Margolin at the conference, in 2024 the FDA defined AMT-130 as a regenerative medicine advanced therapy (RMAT).

 

This category includes life-threatening diseases such as HD. Dr. Margolin said it is applicable to new kinds of drugs such as gene therapy, cell therapy, and tissue-engineered products, and it further accelerates FDA review.

 

In achieving this designation, uniQure presented to the FDA the data from the Phase 1/2 trial, and the FDA agreed that this data can serve as the primary basis for a drug application, Dr. Margolin said.

 

Dr. Margolin indicated that this determination means that uniQure will not need to put AMT-130 into a Phase 3 trial.

 

“An additional investigational study will not be required,” he emphasized. “That accelerates by several years the timeframe in which AMT-130 might become available to a wider U.S. cohort of patients.”

 

Swaying the FDA to be more flexible

 

Because of the lack of therapies that modify the course of this rare and devastating disease, the uniQure project and the company’s dialogue with the FDA have indicated the willingness of the agency to allow flexibility in clinical trial programs and a faster timeline.

 

Dr. Margolin’s talk title included the phrase “alignment on a US Regulatory Path Via RMAT.” Alignment with the FDA could lead to an “accelerated approval” for AMT-130, he observed.

 

Dr. Margolin asserted that uniQure’s dialogue with the FDA “has meaningfully advanced HD regulatory science.”

 

In response to a question from Dr. Pacifici about the negotiations with the FDA, Dr. Margolin stated that uniQure hopes that the lack of disease-modifying therapy is “swaying FDA to be more liberal than they have been in the past.”

 

Dr. Pacifici asked what additional studies uniQure will conduct if it secures the accelerated approval, which would still be only conditional.

 

Dr. Margolin replied that uniQure will discuss that matter with the FDA.“Importantly, even an accelerated approval means the drug will be available to patients,” Dr. Margolin stressed. “It does constrain promotional materials in certain ways, but would have no relevant impact on its potential availability and accessibility to U.S. patients.”

 

A Breakthrough Therapy designation

 

AMT-130 gained RMAT designation because it is a gene therapy. Since the conference, the AMT-130 program has made yet further progress.

 

On April 17, uniQure announced that the FDA granted Breakthrough Therapy designation to AMT-130.

 

“Receiving Breakthrough Therapy designation underscores both the urgent need for effective treatments for Huntington’s disease and the encouraging interim data demonstrating that AMT-130 has the potential to slow disease progression,” said Walid Abi-Saab, M.D., chief medical officer of uniQure, in a press release. “We look forward to working closely with the agency to bring AMT-130 to the Huntington’s disease patient community as quickly as possible.”

 

As explained in the press release, Breakthrough Therapy designation for AMT-130 means that the drug “may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).” 

 

The firm expects to provide a further FDA update this quarter. In the third quarter, it aims to present data on AMT-130 to support its potential drug application submission.

With ‘great promise’ for treating Huntington’s disease, four drug programs press ahead (Part I)

 

At the recent 20th Huntington’s Disease Therapeutics Conference, four companies provided updates on their key clinical trial programs, demonstrating that they had overcome basic safety hurdles and revealing plans to have their drugs potentially approved as therapies (treatments) for delaying the progression of HD symptoms.

 

PTC Therapeutics, Roche, Wave Life Sciences, and uniQure made 15-minute presentations. This clinical trials update took place during the first session on February 25, the first day of the three-day event.

 

Sponsored by the nonprofit CHDI Foundation, Inc., the largest private funder of HD research, the conference took place in Palm Springs, CA.

 

Possible impact

 

All four programs use drugs to lower the amount of harmful mutant huntingtin protein in the brain cells of patients. Blocking the bad protein could help prevent the death of brain cells, a major driver of HD.

 

In a post-conference interview with me, CHDI Chief Scientific Officer Robert Pacifici, Ph.D., said that the companies’ plans to move their programs towards drug approval is “great news.”

 

“All of them expressed their commitment to moving forward with their interventions, and that’s not trivial,” Dr. Pacifici said. “That means a lot of time, a lot of money invested on their part. They wouldn’t be doing it if they didn’t think there was great promise there.”

 

Each firm has overcome the basic safety hurdles necessary for moving to a Phase 3 clinical trial, the final step before the U.S. Food and Drug Administration (FDA) approves a drug, Dr. Pacifici added.

 

This article, the first of two, focuses on trials from PTC and Wave. Part II will examine the Wave and uniQure updates.

 

Votoplam, a potential pill for HD

 

With 60 companies represented at the conference, CHDI selected those “that had something new to say” in terms of clinical development, Dr. Pacifici told the attendees.

 

Amy-Lee Bredlau, M.D., PTC’s senior medical director, began her talk on the company’s huntingtin-lowering drug by noting progress: the compound, PTC518, is now called votoplam, a nonproprietary drug name assigned by PTC’s new, larger partner on the project, the international pharmaceutical firm Novartis.

 

“I think this is a really great collaboration,” Dr. Bredlau said.

 

As Dr. Bredlau explained, votoplam is a huntingtin splicing modulator, reducing the production of both the mutant and normal huntingtin proteins.

 

In contrast with riskier delivery methods, some presented in the session, votoplam is a pill. That makes it easy for patients to take the drug.

 

CHDI and PTC started the search for a huntingtin-lowering pill with a joint project initiated in 2018.

 

A delay in HD progression

 

PTC ran a successful Phase 1 clinical trial of votoplam in 2020 and 2021, providing initial evidence of safety and the lowering of the huntingtin protein.

 

At the conference, in an interim analysis, Dr. Bredlau presented data from the first 32 of the 156 volunteers enrolled in PIVOT-HD, PTC’s one-year global Phase 2 trial, which has verified the safety and tolerability of the substance. The first group of participants in PIVOT-HD began in 2022.

 

PIVOT-HD demonstrated that, by the third month, votoplam enters trial volunteers’ brains and lowers the huntingtin protein, she said. At month 12, the lowering was sustained. The trial also showed no spikes in neurofilament light chain (Nfl), a protein whose presence indicates degeneration of brain cells in diseases like HD. Scientists hope that lowering huntingtin will limit Nfl.

 

Significantly, Dr. Bredlau observed that these volunteers had a delay in the progression of HD symptoms, as indicated by several key clinical measures.

 

She said PTC is “very excited” about those trends, which “look very promising,” adding that “we’re really hopeful that we’ll see a strengthening of the signal at the end of the 12-month study,” when results from the remaining volunteers will be studied.

 

PTC will release full results of PIVOT-HD in this (second) quarter of 2025, said Dr. Bredlau, adding that the firm hopes that the results secure permission for a Phase 3 trial, to be run by Novartis.

 

Dr. Amy-Lee Bredlau of PTC Therapeutics presents data from the PIVOT-HD clinical trial demonstrating trends of a delay in progression of Huntington's disease symptoms (photo by Gene Veritas, aka Kenneth P. Serbin).

 

GENERATION HD2 fully in progress

 

Peter McColgan, M.D, Ph.D., global development leader for Roche, updated the pharmaceutical giant’s HD program. He focused on the Phase 2 trial of the huntingtin-lowering drug tominersen.

 

Tominersen is an antisense oligonucleotide – a “laser-guided missile” against HD – originally developed by Ionis Pharmaceuticals, Inc. Like votoplam, tominersen lowers both the normal and mutant huntingtin protein.

 

After Roche’s unsuccessful trial of tominersen in 2021, the company redesigned a less ambitious and more focused trial of the drug in people less affected by the disease. Called GENERATION HD2, it started in early 2023.

 

Dr. McColgan reported that GENERATION HD2, by January, had fully recruited its target of 301 volunteers at 70 sites in 15 countries.

 

“This is a massive achievement,” he said.

 

The trial will assess tominersen’s safety, the use of biomarkers (signs of a disease and a medication’s efficacy), and the drug’s effectiveness.

 

Tominersen is not a pill. It is administered via a spinal tap.

 

Roche aims to complete the trial by the end of 2026.

 

Dr. Peter McColgan of Roche with a slide showing the global recruitment for the GENERATION HD2 clinical trial (photo by Gene Veritas)

 

Roche’s multiple approaches

 

Dr. McColgan also described how Roche has expanded its focus to include other possible HD treatments and related research.

 

“We believe the fastest way to get treatments to patients is to pursue multiple programs in parallel,” Dr. McColgan said.

 

In collaboration with its colleagues at Spark Therapeutics – acquired by Roche in 2019 – Roche scientists are exploring other potential molecules for targeting HD. Spark specializes in gene therapies.

 

HD researchers continue to weigh the approach of drugs such as votoplam and tominersen, which lower both the mutant and normal huntingtin protein, versus those that attack only the mutant. The latter types are known as allele-selective. They leave the normal protein to carry out its essential actions unhampered.

 

Dr. McColgan said that Roche and Ionis are investigating an allele-selective antisense oligonucleotide.

 

Roche is also participating in the HD Regulatory Science Consortium. Using data from the original tominersen trial and other patient data, this collaboration seeks to improve the measurement of clinical trial volunteers’ performance in clinical trials, said Dr. McColgan.

 

Roche is also collaborating with CHDI to improve the measurement of Nfl (neurofilament light chain) as a key biomarker.

 

“Nfl increases across the stages of HD,” Dr. McColgan observed.

 

The latest news on tominersen

 

All clinical trials are regularly checked by an independent data monitoring committee.

 

Volunteers in the tominersen trial not on placebo have received either 60mg or 100mg of the drug.

 

On April 17 Roche issued a letter to the HD community stating that the committee overseeing the tominersen trial has found “no concerns … regarding participant safety or signs of symptom worsening with either tominersen dose.”

 

In addition, the letter said, “the 100mg dose was found to be more likely than the 60mg dose to result in clinical benefit. Therefore for the remainder of the study only the 100mg dose will be tested against placebo, and the 60mg dose will be discontinued.” Those receiving 60mg will now get 100mg.

 

“We are incredibly grateful to the 301 participants and their companions enrolled in GENERATION HD2,” the letter stated. “Each study visit contributes to collecting data that helps the entire HD research community learn more about tominersen, Huntingtin-lowering strategies, and the further understanding of HD.”

 

In Part II of this article I will report on Wave’s and uniQure’s clinical trial updates

 

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

More optimistic than ever, CHDI head scientist sees unprecedented mobilization in the fight to treat Huntington’s disease

 

In the wake of last week’s 20th Annual Huntington’s Disease Therapeutics Conference, the chief scientific officer for CHDI Foundation, Inc., declared that HD scientists had mustered unprecedented efforts toward therapies (treatments).

 

“I’ve been in the drug discovery business for over 30 years now,” Robert Pacifici, Ph.D., the CHDI head scientist, told me in a 37-minute video interview after the conference, referring to the key theme of crucial modifier genes, a focus of the meeting. “I’ve never seen the mobilization of efforts as quickly and as deliberately – from the identification of those genes to the understanding of how those genes mechanistically are having their effect – to actually developing candidate therapies that are modifying those processes.”

 

Dr. Pacifici observed that, in the HD field, “everybody’s pushing wherever they can to accelerate therapeutics. But we all know that sometimes you just hit roadblocks, you hit bottlenecks.”

 

He said that those difficulties can be overcome with “new technologies, new methods, new techniques,” which often result in “breakthrough moments. They allow you to do things that you just could never contemplate doing before.”

 

Dr. Robert Pacifici, wearing a Team Hope shirt from the Huntington's Disease Society of America, overseeing the 20th Annual HD Therapeutics Conference (photo by Gene Veritas, aka Kenneth P. Serbin)

 

The efforts forming around this hottest of topics in the HD field are “incredibly exciting,” Dr. Pacifici said. The “big news” over the next two years should include getting drugs that imitate the effect of the modifier genes – which research has demonstrated delay the onset of HD symptoms – into clinical trial programs.

 

As reported in this blog, the now defunct Triplet Therapeutics had aimed from 2020-2022 to develop and test a modifier gene drug (click here to read more).

 

Dr. Pacifici said that he is “more optimistic” than ever that HD drugs will get approved.

 

I attended the conference. Below you can watch a video of my interview with Dr. Pacifici.

 

 

 

Attacking the harmful protein

 

While this year’s Therapeutics Conference did not include any major positive announcements like the approval of a drug, Dr. Pacifici observed that it also did not bring the kind of disappointing news experienced by the HD community in 2021 with negative results from trials run by Roche and Wave Life Sciences.

 

The conference did bring reports from both Roche and Wave about their revised clinical trial programs. PCT Therapeutics and uniQure also reported on their ongoing clinical trials.

 

All four programs use drugs to lower the amount of harmful mutant huntingtin protein in the brain cells of patients. This is the first of three approaches to defeating HD, Dr. Pacifici recalled.

 

I will detail these updates soon.

 

‘Lucky’ and ‘unlucky’ genes

 

The second, more recent approach involves the search for drugs to imitate the modifier genes, as Dr. Pacifici noted above. These genes are related to somatic instability – the tendency of the expanded HD gene to expand further with time. This process can be triggered by negative modifier genes.

 

Dr. Pacific described those genes as “lucky” or “unlucky.” A good modifier gene can delay HD onset, whereas the bad one can hasten the start of the disease, he explained.

 

These genes act as “sentinels” in the bookkeeping of our DNA, Dr. Pacifici added. “We want our DNA to stay clean and error-free.”

 

Dr. Pacifici emphasized how more than 12,000 HD-affected individuals and their relatives in genetic research helped lead to the discovery of the modifier genes a decade ago. A study of a large group of people’s DNA is known as a Genome Wide Association Study (GWAS).

 

Fixing broken cells

 

The third approach to treating HD involves yet another set of genes that emerged from the HD GWAS. They were a key topic at the conference.

 

Dr. Pacifici stated that these genes are “every bit as validated” as the ones involving somatic instability. “We just don’t know the effect yet,” he said.

 

Dr. Pacifici added that understanding these genes will help answer a key unanswered question about HD: “what is it actually inside a cell at the molecular level that’s broken” and how to fix it.

 

All three of these areas could be targeted by an eventual cocktail of HD drugs, Dr. Pacifici said.

 

Key new genetic research and ‘rock star’ HD families

 

“We keep on thinking of ways of getting even more information out of persons with HD,” Dr. Pacifici said.

 

CHDI has announced that all 22,000 participants in Enroll-HD, the global registry of HD patients and relatives, will be full-genome-sequenced. That means their entire DNA will be  mapped.

 

“That’s a lot of data,” Dr. Pacifici noted. “It’s going to be the next set of breakthroughs, where we understand not just little bits of DNA information but the whole story for every participant.”

 

This will be “incredibly impactful,” he said.

 

The HD families that have provided all of this crucial data underlying these approaches to treatments are true “rock stars,” Dr. Pacifici said. Their interaction with HD scientists is critical, he concluded, to advancing scientific breakthroughs.

At HDF symposium, a Huntington’s disease ‘hero’ who prays for scientists to find a cure

 

Recognizing the invaluable input from people living with Huntington’s disease, the Hereditary Disease Foundation (HDF) featured a conversation with Michael, a 62-year-old HD-affected Boston man, at its biennial conference of scientists seeking therapies for this incurable disorder.

 

Michael was interviewed about his HD symptoms by neurologist Diana Rosas, M.D., of Harvard University and Massachusetts General Hospital.

 

Titled “Living with Huntington’s Disease: Family Perspectives,” this HDF tradition of focusing on an HD-affected person took place on August 8 during HD2024: Milton Wexler Biennial Symposium. Convening some 300 researchers, biopharma officials, and advocates, the event ran August 7-10 at the Royal Sonesta Boston Hotel in Cambridge, MA.

 

HD usually impedes speech. I saw that affecting my mother. She died of the disorder at 68 in 2006, after two decades of symptoms, and I carry the HD gene.

 

Michael struggled but persistently formed words and sentences. “I pray for everybody,” Michael said, referring to the quest for therapies, during the Q&A after the interview.

 

Michael’s former wife attended in support of his advocacy, as did his two sons, both in their 20s.

 

Michael (left), who has Huntington's disease, and his physician, Diana Rosas, M.D. (photo by Gene Veritas, aka Kenneth P. Serbin)

 

A diagnosis in 2017

 

Born in Chicago, Michael grew up in Princeton, NJ. As a young adult he moved to Boston, where he studied to become a French chef. He spent a year traveling through France to master his profession. He worked in several restaurants in Boston and also at Gillette Stadium for the NFL’s New England Patriots.

 

Michael believes his father had HD, although he was never formally diagnosed, due to the limited knowledge about the disease as Michael grew up in the 1970s. His father was also an alcoholic. Michael’s aunt also suffered from HD and went into a care home.

 

Michael was diagnosed with HD in 2017.

 

It became ‘too dangerous and messy’ to cook

 

Dr. Rosas is Michael’s physician. As she noted, many lab researchers have little contact with HD-affected individuals. The interview aimed to inform them of the complex triad of symptoms and many psychosocial challenges posed by HD.

 

Dr. Rosas asked Michael to address questions about the first type of symptoms: movement disorders, including involuntary movements.

 

These symptoms, Michael explained, caused him to stop cooking: it had become “too dangerous and messy.” It also became harder to dress himself.

 

Typical of HD patients (including my mother), Michael has suffered several serious falls, leading to a broken wrist, ribs, neck, a punctured lung, and a subdural hematoma (a serious injury to the head). Though he had participated in research conducted by Dr. Rosas, the hematoma has prevented him from participating in clinical trials, because of a restriction by pharmaceutical companies.

 

“I like helping out however I can,” he said of his participation in research.

 

Michael, who lives alone, does have a chocolate labrador retriever that he walks.

 

Michael used to drink alcohol daily and smoke heavily. The drinking caused one of his falls, he said. He quit both habits. Alcohol was a “big part” of his life, he recalled, adding that he doesn’t “miss the days of drinking.”

 

A greatly modified daily routine

 

Dr. Rosas brought up another part of the HD triad: cognitive loss, executive dysfunction, and failing memory.

 

Michael observed that his loss of executive function prevented him from cooking, which had required preparing items and “lots of multitasking.”

 

Though he “can remember my bank card number,” he has ongoing difficulties with memory. He pays his cable and phone bills but has an accountant to assist with his overall finances. He still cares for two salt-water fish tanks, an activity he took up in his 20s.

 

Michael arises at 6 a.m., when he takes his medications: risperidone, an antipsychotic, twice daily; deluxotine for depression; and a multi-vitamin. He also takes medical marijuana.

 

After some small accidents, Michael stopped driving, now relying on Uber.

 

Overcoming impulsiveness and depression

 

Regarding the third part of the triad, psychiatric and mood disorders, Dr. Rosas observed that HD-affected individuals can become fixated or impulsive.

 

Michael agreed that this has affected him, recalling that his drinking also led him to be “very impulsive.” He also suffers from depression. Many HD-affected people become angry when faced with unexpected changes in their daily routine. Michael has also experienced this type of anger. Getting over the anger can take time, he added.

 

Like many of the affected, Michael also has difficulties sleeping. His drinking had exacerbated this problem.

 

“It’s like your mind and body are always on with HD,” he observed.

 

Indeed, HD-affected individuals burn lots of calories. Dr. Rosas recommends five meals per day, although Michael said he eats three to four. 

 

Dr. Rosas interviews Michael about his HD symptoms (photo by Gene Veritas).

 

‘You are a hero!”

 

In the Q&A following the interview, Michael expanded on aspects of his life.

 

One has involved his relationship with his ex-wife and sons. Michael said that the divorce occurred around the time of his diagnosis and was “probably” the result of it.

 

Michael saluted his former spouse as “one of my huge supporters. I haven’t had a girlfriend after my divorce. We were married for 24 years.”

 

He said that he has “two great kids” who are “successful and happy.”

 

Michael also socializes with friends, some of them also divorced.

 

Asked about the work of the researchers, Michael said, “I love them to death.” He added that he is looking forward to new advances.

 

Dr. Rosas asked what most worries Michael about HD.

 

“I suppose going to a home, going to an assisted living situation,” he said.

 

His capacity to manage on his own prompted praise. “You are a hero!” declared Tacie Fox, a family advocate and co-trustee of The Fox Family Foundation (which supports HD research), leading the audience to applaud enthusiastically.

 

“It feels like you have somehow navigated in a way that brings you joy in your life,” she added. “We’re struggling with that with my little sister. She watches a lot of TV. I’m in awe that you, living on your own, have marshaled that inner strength.”

 

The key role of modifier genes

 

At 64, I have been extremely fortunate to have not been diagnosed with HD. It is likely that I have benefited from modifier genes and other factors.

 

Like the rest of the audience, I was deeply moved by Michael’s courage and perseverance in living with HD.

 

I hope that when the inevitable symptoms arrive, I will have the same strength as Michael.

 

Stay tuned for upcoming articles on the conference proceedings, including deep discussion of the key role of modifier genes in the search for therapies.

 

Disclosure: the Hereditary Disease Foundation covered my travel expenses.