Overflow audience at 13th annual Huntington's Disease Therapeutics Conference

With more than 350 Huntington’s disease researchers and pharmaceutical executives in attendance, the 13th annual HD Therapeutics Conference got underway last night in anticipation of key presentations on progress towards treatments, including the successful Phase 1/2a Ionis Pharmaceuticals gene-silencing clinical trial completed late last year.

Sponsored by CHDI Foundation, Inc., the nonprofit virtual biotech focused on the search for HD treatments, the conference runs through March 1 at the Parker Palm Springs hotel (which is less than three hours’ drive from my San Diego home). In the last presentation, Ionis clinical trial administrators will present the results of the Phase 1/2a study of the company’s HD, drug IONIS-HTT_Rx.

“The first day we opened up the registration, we were almost full at the Parker immediately,” Robert Pacifici, Ph.D., CHDI’s chief scientific officer, said in his opening remarks in the main conference room, which holds 300 people. “We actually ended up allowing 365 participants to register. Not everybody can fit in this room.” So, for the first time at the Parker, CHDI arranged for an overflow room, with a screen projecting the proceedings.

After cancellations, a total of some 350 are expected to attend, one of the largest audiences in the history of the conference.

Dr. Pacifici also presented a check for $38,000 to Louise Vetter, the CEO of the Huntington’s Disease Society of America (HDSA).

As a research organization, CHDI provides no family services such as support groups and care centers. Demonstrating their commitment to HDSA’s mission in these areas – essential for developing treatments – Dr. Pacifici and five other riders (mainly from CHDI) raised the funds in a recent 100-mile biking competition in the Southern California desert.

You can watch Dr. Pacifici’s introduction in the video below.

CHDI Conference Opens with Overflow Crowd from Gene Veritas on Vimeo.

‘Huntingtin lowering’ and other main themes

Scientists and patient advocates eagerly await the March 1 presentation of the Ionis Phase 1/2a clinical trial, in which IONIS-HTT_Rx successfully lowered the amount of the mutant huntingtin protein in participants’ cerebrospinal fluid.

The trial aimed not to study efficacy but safety and tolerability. The next phases of the trial remain a major hurdle: to test whether the drug can actually alleviate or reverse symptoms.

The Ionis contingent at the conference includes Frank Bennett, Ph.D., Ionis senior vice president of research and the franchise leader for the company’s neurology programs, and Anne Smith, Ph.D., the Ionis director of clinical development and the individual responsible for the day-to-day management of the trial.

Dr. Smith will present the Ionis results along with Sarah Tabrizi, FRCP, Ph.D., of University College of London, the lead clinical trial site.

In addition to so-called “huntingtin lowering” strategies such as the Ionis drug, the main conference themes include potential therapies for fixing brain circuitry; the use of stem cells to better understand HD and develop treatments; the interplay of the huntingtin gene and DNA dynamics; and huntingtin protein structure and function.

The opening day also featured a resource fair, with research tools and databases available for HD research and developed by CHDI, partner organizations, and contract research organizations.

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

Jen Ware, Ph.D., CHDI's director for experimental design (right), explains a new CHDI research resource, the Independent Statistical Standing Committee, intended to provide independent, unbiased evaluation and expert advice regarding experimental design and statistics (photo by Gene Veritas).

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.)

Faith in each other: sticking together through the challenges of Huntington's disease

This article is dedicated to my lovely wife Regina and to HD caregivers.

In 2017 my wife Regina and I marked 25 years of marriage with several celebrations, including a May dinner in Rome before meeting Pope Francis at #HDdennomore and then at one of our favorite San Diego restaurants on our anniversary, December 8.

Throughout last year, I relished the many triumphs of our life together: establishing successful careers, building important friendships, and raising our daughter Bianca, who will graduate from high school in June.

I have also reflected on how Regina and I have confronted the ordeals of Huntington’s disease, the debilitating, genetic neurological disorder that took my mother’s life twelve years ago this month. Because I too carry the HD gene, I will inevitably develop symptoms.

Last year, former San Diego Chargers PR director Bill Johnston exemplified the commitment to caregiving when, after 38 years with the team, he skipped its transfer to Los Angeles to keep his wife Ramona in an award-winning HD care facility.

“He didn’t run away from his marriage vows,” HD community member Dave Elliott reacted to the news in a Facebook comment. In HD families, those vows imply a heightened commitment.

Gene Veritas (aka Kenneth P. Serbin) and Regina Serbin at the Vatican Museums, with St. Peter's Basilica in the background, Rome, May 2017 (photo by Bianca Serbin)

Avoiding the HD shipwreck

Regina and I have faced the challenges of HD together.

The day after Christmas 1995, we received the terrible news that my mother had HD, that I had a 50-50 chance of inheriting the genetic defect, and that the children we planned for also faced a risk.

Many relationships shipwreck upon receiving such news (click here to read more).

However, Regina stood firmly by my side. One night, as I lay beside her gripped with fear, she hugged me tightly.

In 1999, Regina sat by my side as a geneticist revealed that I had tested positive for the HD gene.

Seven months later, we shared a tremendous sense of relief with the news that the baby in her womb, our daughter Bianca, had tested negative.

In 2011, Regina sat in the front row as I delivered the keynote address at the “Super Bowl” of HD research, the Sixth Annual HD Therapeutics Conference, sponsored by CHDI Foundation, Inc.

Each day, Regina lives with the fear that she could lose me to HD. Like my “HD warrior” father, who cared for my mother daily for more than a decade, she faces the prospect of watching (and tending) to my slow deterioration and loss of self.

However, not once has she blinked in her commitment.

With faith in each other, and also in the Creator, we have stared down the lion of HD. Striding side-by-side in annual Team Hope Walks, we yearn for an effective treatment.

A healthy relationship might delay onset

Like any long-term relationship, ours has had its ups and downs. Sometimes our different cultural backgrounds (Regina’s from Brazil) have led to disagreements. Overall, though, we have come to accept and appreciate each other’s foibles.

Ken and Regina in front of the Sugar Loaf Mountain in Rio de Janeiro, 1991 (family photo)

We’ve built a united front in running the household, helping Bianca prepare for college, and strengthening the family finances, preparing for the likelihood of my disability.

Whereas my mother’s HD symptoms started in her late 40s, at 58 I have fortunately avoided HD onset.

Scientists are still seeking to explain the differences in onset in people with identical HD mutations like my mother and me. I’ve strived to lead a healthy life, as I’ve chronicled in this blog.

Though the data from studies is complex, science suggests that healthy relationships can help promote overall health.

I firmly believe that I remain asymptomatic in good part because of Regina’s love and support, and because of our shared mission to build a family and raise a thriving child, soon to turn 18.

Treasuring my family

In our frenetic society, and as my aging seems to make life move faster, it becomes easy to take Regina for granted in our daily routines.

I feel a deep need to stop time and savor every moment with Regina and Bianca.

As I've pondered the deeper meaning of our marital commitment, I've focused on what's essential: treasuring them fully.