After other firms’ setbacks, Prilenia readies for readout on Huntington’s drug that improves daily function

 

August brought more difficult news for the Huntington’s disease community with the halting of yet two more clinical trials. However, Prilenia Therapeutics announced at a major research conference last week that it expects to obtain definitive results from a study of a drug proposed to improve function in the early stages of the disease.

 

Prilenia CEO and founder Michael Hayden, M.D., Ph.D., a leading HD scientist, reported that the Phase 3 clinical trial of pridopidine is on schedule, with administrators expected to release results early in the second quarter of 2023. (Click here for background on pridopidine, Dr. Hayden, and Prilenia.)

 

On August 25 Dr. Hayden provided a brief update on the trial, called PROOF-HD (PRidopidine Outcome On Function In Huntington Disease), at HD2022: Milton Wexler Biennial Symposium, sponsored by the HD-focused Hereditary Disease Foundation. It was held August 24-27 at the Royal Sonesta Hotel in Cambridge, MA.

 

If successful, the PROOF-HD trial will result in a landmark not just for HD, but neurodegenerative diseases in general. Its potential significance has increased because of the disappointing results from two important HD gene silencing clinical trials in March 2021 and the news this month that key trials by Novartis and uniQure had to stop dosing because of safety concerns.

 

In an August 27 interview with me, Dr. Hayden explained pridopidine’s benefits.

 

“It's the only drug that has showed some impact on stabilizing TFC [total functional capacity], keeping patients functional, keeping them managing their finances, keeping them at work, keeping them going for walks with their children and grandchildren, keeping them doing activities of daily living for longer,” Dr. Hayden said.

 

Analysis of pridopidine has demonstrated that patients taking the drug showed a slower decline in TFC. In early patients, pridopidine can maintain TFC and slow deterioration

 

Dr. Michael Hayden (left) confers with Peter McColgan, M.D., the clinical director for the HD program at Roche, during a break in the Milton Wexler Symposium (photo by Gene Veritas, aka Kenneth P. Serbin)

 

Neuroprotective effects

 

The earlier, revised analysis of pridopidine led to a “surprising but very welcome result,” Dr. Hayden continued. Pridopidine works as a “highly potent and highly selective sigma-1 receptor agonist.” An agonist is a drug that mimics a natural substance, while sigma-1 is “a molecular chaperone,” a chemical that helps proteins perform the important function of folding. He called pridopidine “the most potent and selective” sigma-1 agonist ever described.

 

In everybody’s cells, decreased sigma-1 has a negative impact on monitoring stress, including for the endoplasmic reticulum, a key organelle (subunit) that manages stress. In HD, this subunit experiences disturbances that cause an imbalance in the cell, Dr. Hayden said.

 

Overall, a reduction in sigma-1 makes neurodegeneration (slow and progressive loss of brain cells) get worse, Dr. Hayden explained.

 

However, pridopidine enhances sigma-1. The drug has “all in all neuroprotective effects,” by reducing cellular stress and even increasing the critical “connectivity” of the brain and the removal of “toxic products.”

 

Critically, pridopidine is “the only [HD] drug that has shown stabilization of neurofilament,” an important marker of disease progression, Dr. Hayden observed. An increase in levels of neurofilament, which makes up a brain cell's scaffolding, indicates dysfunction.

 

A Prilenia poster demonstrating the positive effect of pridopidine on total functional capacity and stabilization of neurofilament (photo by Gene Veritas)

 

A safe and tolerable drug

 

PROOF-HD seeks to confirm pridopidine’s efficacy so that it might be approved as a drug by the U.S. Food and Drug Administration (FDA).

 

“We submitted this to the FDA, and the FDA was hugely supportive,” Dr. Hayden said. Last November the FDA granted pridopidine a “fast track” designation to potentially speed drug approval, because HD is a “significant unmet need,” Dr. Hayden noted.

 

The designation “allows us to have a closer relationship with the regulators as we go through this process,” he said.

 

Despite the coronavirus pandemic, PROOF-HD began ahead of schedule in October 2020 and is on schedule to report results in about eight months. It recruited 499 clinical trial volunteers, more than the goal of 480, at several dozen sites in the U.S., Canada, and Europe.

 

So far, the standard safety monitoring board has found no reason halt the trial.

 

“So that's also encouraging that this is a very safe and tolerable drug,” said Dr. Hayden. 

 

A Prilenia slide with an overview of PROOF-HD, including the main goals (endpoints) (photo by Gene Veritas)

 

Seeking to prevent disease

 

In contrast with other top HD drug programs using brain or spinal injections, pridopidine is taken orally twice daily, “without any need for nursing care,” Dr. Hayden pointed out.

 

If PROOF-HD is highly successful, inviting a priority review by the FDA, Dr. Hayden said that pridopidine could become available for patients in mid-2024.

 

“My vision for pridopidine is that it could become a standard of care for neuroprotection,” Dr. Hayden stated in a January interview. “For diseases where we can define patients who are close to onset of a neurodegenerative condition, an oral therapy with a benign safety profile – which is what we are trying to establish in our current and planned clinical trials – could become a preventative treatment option.”

 

In a January 2021 Huntington’s Disease Society of America (HDSA) webinar, Sandra Kostyk, M.D., Ph.D, the co-principal investigator for PROOF-HD in the U.S., referred to pridopidine as a possible “disease-modifying intervention – something that slows the course of the disease.” The data indicate that early-stage HD patients could obtain “long-term beneficial effects” from an approved pridopidine drug for five years or more, she said.

 

A Prilenia slide about the advantages of small molecule drugs, the preferred method of treatment in HD. Pridopidine is in that category (photo by Gene Veritas)
 

An upcoming update, a caution, and hope

 

On September 7, HDSA will host a webinar further updating PROOF-HD and featuring Dr. Hayden, Dr. Kostyk, and Andrew Feigin, M.D., the trial’s principal investigator in the U.S. Click here to register.

 

“Of course, there's no certainty that this drug will be successful,” Dr. Hayden told me. “Forty percent of Phase 3 trials fail. So, we have a 60 percent chance. In a Phase 3 trial, things fail for all kinds of unexpected reasons, as sadly we've seen in the Huntington's field.”

 

Pursuing successful trials for pridopidine “has been a long struggle for everybody,” Dr. Hayden concluded. “This is hopeful, but we're not there yet. But hold on as we go on this journey as co-travelers in the attempt to find some way to moderate the course of this dreadful illness.”

 

(Future articles will cover other aspects of the Milton Wexler Symposium. Also see @HDBuzzFeed on Twitter and this article.)

 

Dr. Hayden (right) and Nicholas Caron, Ph.D., exchange ideas at the poster session of the Milton Wexler Symposium (photo by Gene Veritas).

‘Darkness replaced by hope and light’: taking stock of Huntington’s disease research

As the Huntington’s disease community in 2015 enters a promising phase of clinical trials for remedies that might slow or halt the progression of the disease, one of the world’s leading HD scientists recently took stock of the significant progress made over the past several decades.

“The horizons for therapy were very far away,” Michael Hayden, M.D., Ph.D., the President of Global Research and Development and Chief Scientific Officer of Israel-based Teva Pharmaceuticals, said during a February 10, 2015, presentation about his company’s latest efforts to defeat HD.

Dr. Hayden recalled how, 40 years ago, HD was virtually unknown in his native South Africa and many other countries. HD-afflicted people faced stigma and were left to cope with their disease “in isolation and despair,” Dr. Hayden remembered of his first contact with the disease as a young medical student.

“It was just a dream then that there would be pharmaceutical companies interested in Huntington disease,” he said. (In some countries HD is referred to as “Huntington,” not “Huntington’s.”)

However, as Teva and other companies work towards HD treatments, the outlook has changed dramatically.

“We are now in a place of really tremendous hope,” Dr. Hayden declared enthusiastically. “The darkness is replaced by hope and light. At the end of the tunnel we are seeing this light now, not only with this [Teva’s] drug but other trials you are hearing about.”

Dr. Michael Hayden (photo by Gene Veritas)

Reexamining a promising drug candidate

Dr. Hayden offered these remarks during a Huntington’s Disease Society of America (HDSA) research webinar titled “Pride-HD: a dose finding, safety and efficacy study of pridopidine in HD patients.” (Click here to watch the webinar.)

Pridopidine was first tested in two clinical trials – in Europe and North America – by the Danish pharmaceutical company Neurosearch. The company, although it observed some interesting effects, did not achieve sufficiently positive results to bring the drug to market.

That’s because the chosen “endpoint” in the study, the way of measuring the drug’s effects, didn’t show a result significant enough for obtaining regulatory approval, Dr. Hayden explained. Neurosearch chose only a subset of motor symptoms as the study endpoint.

But some researchers still believed pridopidine had potential as an HD drug. Dr. Hayden and Teva studied the overall impact of pridopidine and, after obtaining the license for the drug from Neurosearch, have decided to run an additional clinical trial, called Pride-HD (Pridopidine Dose Escalation in HD). Teva is using a different endpoint, the so-called total motor score, a measurement of all the motor symptoms.

Dr. Hayden observed that patients in the earlier pridopidine studies actually showed improvement in motor symptoms caused by HD such as chorea, or involuntary movements. Pridopidine also improved eye movement substantially, he said. It also stabilized levels of dopamine, a neurotransmitter and hormone involved in movement control, mood, and motivation.

Patients’ depression, another telltale HD symptom, also did not worsen, Dr. Hayden noted.

Aiming for broader impact

“There may be some broader affect on other features of Huntington disease,” he added. Additional studies of pridopidine in animals have indicated that it brings about changes in the brain, might be “neuroprotective,” and might help with improving thinking and feeling, he explained.

Therefore, Teva will add other key endpoints to the Pride-HD study: cognition, mood, and quality of life. The study also will assess the effect of dosages of pridopidine higher than those given patients in the earlier trials.

Pridopidine “could theoretically have some effect to change the course of the illness,” Dr. Hayden observed. “And wouldn’t that be exciting?”

Pride-HD enrolled its first patient in April 2014 and will continue throughout 2015. Teva aims to enroll 400 patients at 54 sites in North America, Europe, and Australia. If the results are favorable, Teva could seek regulatory approval for the drug in late 2016, Dr. Hayden said.

As HD specialist Dr. LaVonne Goodman noted in her February 18 commentary on the potential of pridopidine, “recruitment is not going well for Pride-HD.[...] The bottom line is that finding new drugs for HD takes a lot of work, good trials and a long-term commitment from HD families and investigators. If we don't join this or other trials, we will never have new drugs for HD: not for ourselves or the next generation."

To learn more about Pride-HD and how to participate, refer to the above-mentioned link to the webinar or call HDSA at 800-345-4372.

Teva is also conducting a clinical trial of the drug laquinomod for use in HD, Dr. Hayden noted. Laquinomod is thought to reduce the inflammation of the brain in neurological disorders. Click here to learn more about the trial.

Another historic moment

As a carrier of the HD gene mutation, I listened to Dr. Hayden’s comments on the long-term progress of HD research with great hope.

Scientists have observed that managing HD effectively likely will require a cocktail of drugs. Pridopidine is yet another potential element in the mix. (I have reported on many of the elements in this blog over the past ten years. Click here and here to see recent examples.)

Having tracked the HD movement for nearly 20 years, I also appreciated Dr. Hayden’s important reminder that the quest for effective treatments is a lengthy process. Science and clinical trials require time and investments of money and intellect.

I wrote this article in Palm Springs, CA, just before the start of yet another historic mark in the HD movement: the 10^th Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc., at the Parker Palm Springs hotel February 23-26. In the past I have referred to this event as the "Super Bowl" of HD research.

In Palm Springs, I will listen to other scientists take stock of the search for HD treatments.

I also expect to witness yet further examples of researchers replacing the darkness of Huntington’s disease with hope and light.

For yet more perspective, watch my interview with Dr. Hayden at the 2011 HD Therapeutics Conference in the video below.

Gene Veritas interviews Huntington's disease expert Michael Hayden from Gene Veritas on Vimeo.

‘Alive and Well’ captures struggle against untreatable genetic brain disorder

Watching the recently released documentary film Alive and Well this past Monday evening, I re-experienced the torrent of emotions involved in the fight against Huntington’s disease.

Filmed on three continents, the 75-minute Alive and Well takes us on an odyssey through the lives of six families affected by HD and one HD researcher whose “reason for getting up in the morning is just to do something to solve this problem.”

The stories embody the deepest fears and highest hopes of the HD community.

Alive and Well portrays the utter helplessness of HD patients in the final stages of the disease. The filmmakers visit a medical facility where several HD patients reside. Their bodies appear almost lifeless as they sit in chairs, unable to care for themselves. Their faces are half-frozen, revealing only a wisp of the personalities they once expressed.

These HD people are in a movie, but they cannot even speak their lines.

Honoring HD people, creating an advocacy tool

“Huntington disease has been described as the most devastating disease known to man, and it’s devastating because it robs you of who you are,” says world-renowned HD scientist Dr. Michael Hayden, interviewed in his native South Africa. “You lose the ability to speak. You lose the ability to communicate. Yet your perception is fine. You can perceive things around you.”

Dr. Hayden uses “Huntington disease,” the way people spell the term in Canada, where he has spent much of his career.

“The other devastating part of this is that it’s progressive,” he adds. “There is no way to intervene in the course of the illness. And what’s particularly ironic is that it’s continuous from one generation to the next.”

In their struggles, Huntington’s families provide great inspiration for humanity, “so-called ordinary people doing extraordinary things,” Dr. Hayden continues.

“If people knew the stories that are in these families with Huntington disease, these would fill books and books of adventures and sources of inspiration for the rest of the world. The stories are really profound.”

As the filmmakers say, Alive and Well is about a disease that exists everywhere but is still unknown. It’s also about human resilience.

“We made this film to honor the people who trusted us with their stories, to have this film seen by as many people as possible and to raise awareness of Huntington's disease,” says director Josh Taft, first introduced to HD by Seattle advocate Liz Weber, in a press release. “We wanted a way to share these very personal stories with compassion, strength and beauty. We wanted to create a solid tool for the community to share their stories and to be proud of.”

No regrets

Viewing the film in a downtown San Diego movie theater at a screening organized by Misty Oto of the local chapter of the Huntington’s Disease Society of America (HDSA-San Diego), Alive and Well carried me through the peaks and valleys of my own experience with HD.

My mother was diagnosed with HD in 1995 and died in 2006 at the age of 68. I tested positive in 1999; thankfully, I have yet to show any of HD’s classic symptoms. Our daughter tested negative in the womb and is today a thriving eighth grader.

In the first profile, of 19-year-old Heather Alimossy of Medford, OR, I saw how innocence is lost and life changed forever when someone tests positive for the HD mutation – confirmation that Heather will follow in the footsteps of her HD-afflicted mom.

As shown, Heather forges on in the quest to live a full life. She continues to ride her dirt bike – and she lovingly cares for her mother.

“I don’t want to regret anything,” she says, the film then showing her on a ride through the countryside.

Taking a chance

I was heartbroken by the story of Katy Bradley and her family, of Olympia, WA. Katy married Scott despite learning that his father had HD. At one point, the couple visited him in a nursing home in California.

“I knew by then, especially, what this could turn into,” Katy says. “I guess I took a chance.”

The couple refused let HD “ruin” their lives. They decided to bear children without Scott getting tested. However, without their knowing it, Scott passed on the HD gene to their son Matthew. Scott’s symptoms didn’t begin until well into his adult years, but Matthew developed juvenile HD as a toddler.

In a matter of a few years, Matthew’s symptoms worsened to the point where he was “in a constant state of seizure,” Katy says. “His brain is constantly firing.”

“Today’s it,” says Katy. “So let’s have fun today. So let’s do what we can. Let’s make muffins.”

The vignette finishes with people quietly attending Matthew’s burial. The couple’s small daughter Anna is also at risk for HD. Meanwhile, Scott continues to decline.

A very hopeful note

The other profiles in the film focus on Courtney Rifkin, a gene-positive woman shown climbing Mount Kilimanjaro to raise awareness about HD; Brooks and Dunn drummer Trey Gray, portrayed in his desperate struggle to maintain his skills after HD onset; Mandy Kipfer, a young woman who wants to start a family, filmed as she receives her HD-negative test result; and the middle-aged former NBC News war correspondent Charles Sabine, presented in his role as the HD community’s global advocate while striving to avoid onset.

I could empathize deeply with Trey, because I fear losing my ability to write. I felt terribly jealous of Mandy, although ultimately happy for her, because I want to be free from the shackles of HD. I felt strengthened by Courtney and Charles, because they refuse to give up and are willing to share their stories with the world.

During the film, I sat next to HDSA-San Diego president George Essig, whose extended family is affected by HD. He, too, was moved by Alive and Well.

“It’s been the best representation really of the disease I’ve seen on a variety of levels – physical, emotional, and in terms of the devastation,” George said afterwards, as the audience of 140 filed out of the theater.

The film features an original score plus songs from Radiohead, Pearl Jam, Fleet Foxes, and Sigur Ros. The overall effect is saddening but also upbeat.

“I would also say it has a very, very hopeful note,” George said.

HDSA-San Diego president George Essig with daughter Julia and wife Theresa at the screening of Alive and Well (photo by Gene Veritas)

Spreading the word

George added that he is “anxious to get copies out, because I think we could spread this virally as well as in movie theaters and a part of the whole education process and awareness process for the Huntington’s community.”

Alive and Well is not yet available on DVD and currently can only be viewed in small screenings, but event organizer Misty pledged to advocate for greater distribution of the film.

Alive and Well has shown in a number of other U.S. cities. Advocates can arrange for showings in their communities by contacting the Theatrical on Demand organization GATHR.

“We’re incredibly proud that Liz Weber and the team in Seattle developed this film,” said HDSA CEO Louise Vetter in a phone interview today. “There are a lot of multimedia tools to raise awareness about HD. We’re supportive of all the efforts.”

The producers aim to “bring the film to life” by encouraging HD families to share the opportunity to view it, Louise added. It’s also a way for HD community to “learn how to be alive and well with HD,” she said.

“That’s a very powerful effort,” she observed of the film’s promotion, which has relied heavily on social media. “They’ve been very committed to that grassroots effort from the beginning.”

In recent years, a number of advocates have been producing other films on the disease. Notable examples include: Chris Furbee’s just-completed, 89-minute Huntington’s Dance, chosen to appear at the 2014 edition of the highly competitive Slamdance Film Festival; Kristen Powers’ still- in-progress Twitch; and James Valvano’s still-in-progress The Huntington’s Disease Project: Removing the Mask.

(To read more on HD’s place in the news and entertainment media, click here.)

Yesterday, polio – tomorrow, HD?

Alive and Well begins – and ends – with a message of hope from Dr. Hayden.

“For each of us, we have to find our own passion,” he says at the outset. “That’s what makes life meaningful.”

We all can and must contribute, Dr. Hayden urges us.

“When you grow up in (apartheid) South Africa, you learn very quickly not to accept dogma,” he recalls of his youth in the closing minutes of the film.

Nobody believed HD existed in Africa, he adds. “Unfortunately, it’s alive and well throughout Africa.”

He recounts how, in conducting his Ph.D. research on HD in South Africa, he visited every mental hospital in the country to attempt to measure the frequency of HD among the populace.

Today Dr. Hayden is focused on the pathways to treatments that, although they may not cure the disease, could delay onset to offer people a longer life. (In 2012, Dr. Hayden became the president of global research and development and chief scientific officer for Teva Pharmaceuticals, Inc., a large, Israel-based drug firm, where he continues to promote HD research.)

“I’m really hopeful that we are going to be able to change the course of this illness,” he concludes, “and I think it’s in the near as opposed to distant future. I don’t know what ‘near’ is, but I’m convinced that with the … incredible donations of organs and blood and stories and financial support that’s come from so many quarters that we’ll be able to do something….

“Who would have thought in the late ‘50s there’d be treatment for polio? We can and will overcome this.”

The first dose is hope: moving towards treatments for Huntington’s disease

With its incurable genetic attack on the brain, Huntington’s disease wreaks havoc on its victims and their families, leaving them helpless, bereft of hope. I felt powerless as I watched my own HD-stricken mother become a mere shadow of herself and then worried about my own onset after testing positive for HD in 1999.

However, we have reason for hope. After many years of quiet but steady progress, drug makers are beginning to harvest significant results in the quest for treatments.

Since my mother’s death in 2006, I have seen scientists move from cautious optimism to optimism and now to genuine optimism.

At the 7th Annual HD Therapeutics Conference last week in Palm Springs, CA, I observed how many of the world’s leading HD researchers are preparing for clinical trials of remedies that could prolong and improve the lives of patients – and prevent me from becoming symptomatic. Notably, this year’s conference included many pharmaceutical companies: Alnylam, Isis, Medtronic, Novartis, Pfizer, Sangamo BioSciences, and Vertex.

As I participated in the conference, I felt hope come alive for the HD community.

Scientists pushing forward

I witnessed hope in the scientists’ confident smiles, animated conversations, and enthusiastic handshakes – including that of Dr. Robert Pacifici, the chief scientific officer of CHDI Management, Inc., the multi-million-dollar HD treatment initiative and the organizer of the conference.

Dr. Robert Pacifici (left) and Gene Veritas

“There are now eight things with the potential to reach the clinic in a two-year time horizon and a bunch more behind that,” Dr. Pacifici told me in an interview.

I also encountered optimism in Dr. Jim Gusella, whose research team found the general location of the HD gene (the marker) in 1983 and, in 1993, cloned it, making possible a simple, 100-percent accurate genetic test for the disease.

In many ways, his historic work laid the foundation for today’s advances. His current work includes the search for modifier genes – genes that, in addition to the HD gene, might affect the onset of the disease.

But scientists require an engaged HD community. In an interview, Dr. Gusella told me that patient participation is “incredibly important” in the drive for treatments.

“You cannot study a human disease without studying the people who have the human disease,” he explained. “You can’t test a drug unless you have people to test it on to see whether it does anything. The more they can participate, the better, whether it’s just giving a blood sample or going in and having neurologic exams to look at progression of disease or participating in a clinical trial.”

And, Dr. Gusella added, the community must maintain hope.

Dr. Jim Gusella (left) and Gene Veritas

Lowering huntingtin

Above all, I saw hope personified in the conference’s two dozen presentations and nearly 100 posters – all of them focused on the goal of understanding HD more deeply and/or developing treatments.

As I strived to process the vast information of this highly compressed 72-hour event, I felt exhilarated at the prospects of being freed from the threat of HD.

I paid special attention to the sessions on “lowering huntingtin,” a variety of strategies for reducing the amount of defective protein in brain cells. These strategies seek to block HD at its genetic roots, thus ameliorating or preventing symptoms.

I’ve followed one of these initiatives, a collaboration between CHDI and Isis Pharmaceuticals, Inc., since early 2008 (click here to read more).

I was thrilled to watch Dr. Frank Bennett, the Isis senior vice president of research, present an update . This year or next, Isis likely will apply to the federal Food and Drug Administration for a Phase I clinical trial to test the safety of its “antisense” technology, a class of substances known as “oligonucleotides,” or “oligos,” which would interrupt the production of defective proteins.

Isis, CHDI, and academic collaborators such as the HD lab of Dr. Michael Hayden at the University of British Columbia achieved an important breakthrough by discovering a way to lower defective huntingtin proteins while allowing normal huntingtin to carry on its vital tasks in the brain cells.

Isis has demonstrated the feasibility and safety of lowering huntingtin in mice, rats, and non-human primates.

Significantly, the Isis oligos have helped alleviate symptoms in HD mice.

An excellent scenario

Sitting cross-legged on the floor in front of the podium, I snapped photos of Dr. Bennett’s slides and listened intently to each word.

It was like having a front-row seat at a grand theatrical production – but one that was about me and the hundreds of thousands of people around the world affected by HD as patients or gene-positive people awaiting onset.

Dr. Frank Bennett (right) and Gene Veritas (photo by Dr. Ed Wild)

We wait as the actors, these scientific heroes, unravel the plot towards effective treatments.

“CHDI like a dream – couldn’t have imagined a better scenario,” I wrote in my notes. “Incredible vision with gene silencing.”

(Later this year I plan to pay my fourth visit to the Isis labs in Carlsbad, CA, to prepare a detailed update on the project.)

Inspiring connections

As we depend on the scientists literally to save us from HD, they also depend on the HD community for inspiration.

In remarks to the audience, Dr. Ladislav Mrzljak, CHDI’s director of neuropharmacology, recalled my 2011 CHDI keynote speech. Dr. Mrzljak told me personally that my speech had inspired him as he assumed his new role at CHDI after eleven years at the pharmaceutical giant AstraZeneca.

After one speaker noted that a researcher at my alma mater, Yale, had received a CHDI grant, I asked Dr. Mrzljak for details. Not only did Dr. Mrzljak personally know the researcher; he himself had spent the 1990s at Yale studying with world-famous cognitive neuroscientist Patricia Goldman-Rakic.

Dr. Mrzljak presented evidence that a CHDI-designed compound (CHDI-246) produced positive effects as measured in brain samples taken from HD mice. Research on CHDI-246 continues.

Dr. Ladislav Mrzljak (photo by Gene Veritas)

In addition to scientific veterans, this year’s conference included many young poster presenters. I met Julie Harness, a Ph.D. student specializing in HD stem-cell research at the University of California, Irvine (UCI).

Using both normal and HD-affected embryonic stem cells derived from discarded blastocysts from couples who opted for pre-implantation genetic diagnosis, Harness seeks to understand the causes of HD and perhaps develop an approach to treatment, including drug discovery. (Click here for more on California’s HD stem-cell-research. In a future article I will explore UCI’s HD research in depth.)

Harness told me that she felt inspired to present a poster this year after seeing photos of posters from last year sent by another UCI graduate student who had attended the 2011 meeting. Perhaps I took those photos – because I have included poster photos in this blog and since 2010 have supplied CHDI with a CD containing photos of all posters.

Julie is also a reader of this blog.

Julie Harness and her poster on a stem-cell drug-discovery platform for HD (photo by Gene Veritas)

Coming down to the wire

Despite the positive outlook, participating in the conference also magnified my fears of onset. My mother’s symptoms apparently began in her late 40s. At 52, I count each day without the classic symptoms – chorea (shaking), cognitive loss, and mood disorders – as a bonus.

I wondered: will the clinical trials prove successful, and will the medicines come in time to save me? If I become ill, will they help me recover?

As I watched Dr. Sarah Tabrizi’s slides demonstrating significant changes in the brain before classic onset, my heart sank. She stated that these changes begin as early as 20 years before predicted onset.

I glanced over at Jeff Carroll, a recently minted Ph.D. who is emerging as a leader in HD research. His poster – a study of HD mice and cell metabolism that suggests another potential approach to treatment – won first prize. Dr. Carroll, 34, is also gene-positive for HD and, like me, places great hope in the Isis project. His research has contributed to that project.

Dr. Jeff Carroll ponders Dr. Bennett's Isis update (photo by Gene Veritas).

“We’re fried!” I thought to myself as I viewed images of the brain shrinking.

To my relief, Dr. Tabrizi pointed out that, despite significant changes in the brain, “premanifest” individuals maintain an almost normal level of cognitive abilities.

“Despite striking brain changes, premanifest HD gene carriers did not deteriorate significantly over 24 months in cognition or motor function tasks,” she said in reference to the TRACK-HD study that she headed. “I think that tells us that the brain is functionally plastic and is compensating. And the good news is that there may be a lot to rescue.”

“We gene positive are really coming down to the wire!” I wrote in my notes. “Can we hold on??? If I get sick, can I recover with meds? Evidence in mouse trials suggests: yes!”

The first dose

I shook many hands at the CHDI meeting – perhaps even the hands of those who will produce the first effective treatment to stop HD symptoms.

After the conference, we have all returned to the HD trenches.

The scientists must now turn hope into actual treatments.

I must continue my work as an advocate for the Huntington’s Disease Society of America (HDSA).

My task is to carry the message of hope of a treatment to everybody I encounter in the HD community, either in person or online.

Indeed, this must become the priority of HDSA and advocates everywhere.

In an HD treatment, the first dose is hope.

Gene Veritas and CHDI's newly launched logo. Dr. Simon Noble, CHDI’s director of scientific communications, explained to the audience that the new logo symbolizes CHDI as a “drug development organization” seeking “effective treatments” as its first goal. The tree represents the biology and chemistry involved in HD and HD research, clinical developments, neurons, biological pathways, and the hereditary nature of HD. The logo's muted color reflects the “somber nature” of CHDI’s mission. While the initials “CHDI” once referred to “cure Huntington’s disease initiative,” the foundation emphasizes that the initials no longer signify that phrase. "We can worry about curing down the line, however you want to define curing," Dr. Noble stated. (photo by Lev Blumenstein)

(In a future article I will examine the research progress reported at the CHDI conference.)