Chief Huntington’s disease drug hunter: ‘every confidence first treatments’ in the works

Surveying the vast progress in Huntington’s disease research and a “blitz” of clinical trials now in progress, a key scientific leader in the efforts has predicted that they will produce treatments for the incurable neurological disorder.

“I have every confidence that this batch of clinical candidates that are now being tested are going to yield the first treatments for Huntington’s,” said Robert Pacifici, Ph.D., the chief scientific officer for CHDI, the multi-million-dollar non-profit virtual HD biotech.

Dr. Pacifici’s remarks came in an interview on February 24 in Palm Springs, CA, at the organization’s 11th Annual HD Therapeutics Conference, sponsored by CHDI Foundation, Inc., the backer of the initiative.

Nobody can foretell the result of a clinical trial, and Dr. Pacifici did not specify a timeline for an effective treatment reaching the market. However, he offered examples of the immense progress towards developing treatments.

“It’s really frustrating for people, I know, to say, ‘That’s good news, that’s good news, but where’s the treatment, where are the drugs?’” Dr. Pacifici said. “The thing I would point to is that so many of the things we said were going to happen actually have happened. And so many of the things that have happened have actually yielded the outcome that we wanted.”

Dr. Pacifici cited three recent key advances: the ongoing research in biomarkers (signals) to measure the efficacy of potential drugs’ in reducing the harmful presence of abnormal huntingtin protein in brain cells; major progress in identifying modifier genes that delay or hasten disease onset; and the start of clinical trials.

The trials post the most “difficult” challenge in the process, he said.

“We want to make sure that we do things in a way that obviously is very careful,” he said, explaining the primacy of drug safety. “The last thing we want to do is harm anybody.”

Noting that the search for drugs has no guarantees, Dr. Pacifici nevertheless concluded that these are “exciting times” for the community of HD families, researchers, and supporters of the cause.

You can watch my interview with Dr. Pacifici in the video below.


'Every confidence first Huntington's disease treatments' in the works from Gene Veritas on Vimeo.

First Ionis patients safe

Until recent years, such good news seemed like a remote possibility for HD Therapeutics Conference participants and, indeed, for the entire HD community.

Because of the growing number of HD clinical trials and therefore greater hope for effective treatments, Dr. Pacifici and fellow CHDI conference organizers launched a new feature at this year’s conference, the “Clinical Trials Update Blitz.” Representatives from four different trials presented their latest news in 15-minute presentations.

The most anticipated update focused on the historic trial by Ionis Pharmaceuticals, Inc., to attack the root cause of HD via gene-silencing.

Trial principal investigator Sarah Tabrizi, M.D., Ph.D., of University College London reported that all patients in the very first cohort in the Phase 1b/2a trial – aimed at testing primarily safety and tolerability – completed the trial without incident.

Dr. Sarah Tabrizi updating the historic Ionis gene-silencing trial (photo by Gene Veritas)

The first group of participants received the first dosing of the drug, IONIS-RTT_RX, in October 2015. They received three additional doses at 28-day intervals and were monitored by trial administrators.

“We completed Cohort A, in London and Vancouver, four subjects, and the DSMB [independent data safety monitoring review board] met and allowed us to move to cohort B,” Dr. Tabrizi said. (A DSMB, a standard in all clinical trials, halts a study if patient safety is threatened.)

Administrators of the Ionis trial are currently recruiting volunteers for Cohort B, to be followed by Cohorts C and D, as outlined in the plans for the experiment. In all, 36 patients will take part in Phase 1b/2a. If all cohorts are successful, Ionis will seek approval for a full-blown, larger Phase 2 trial to test drug efficacy.

For further background on the trial, watch Dr. Tabrizi’s update in the video below.


First Patients Safe in Ionis Trial for Huntington's Disease Treatment from Gene Veritas on Vimeo

More than a disease

Drawing a record 325 participants from academia, the pharmaceutical business, and the medical field, the conference highlighted cutting-edge HD research, including the structure and function of the huntingtin protein; the huntingtin gene and the human genome; potential gene-silencing treatments; restoration of cell health; and ways to measure clinical trial outcomes.

Although highly dedicated to HD research, many of the non-physician scientists have little if any contact with HD families. This has prompted CHDI to open each conference with a keynote by a representative of the HD community to drive home the human reality of the disease and the urgent need for treatments. (I keynoted the 2011 meeting.)

This year Astri Arnesen and Svein Olaf Olsen, a married couple who have led the HD cause in their native Norway and in the European Huntington Association, delivered a powerful keynote about HD and marital commitment, denial, genetic testing, and raising a family. They titled their presentation “HD – more than a disease!”

Astri and Svein Olaf received a standing ovation.

I will explore their story and provide an overview of the key scientific findings in a second report on the conference.

Svein Olaf Olsen (left) and Astri Arnesen (photo by Gene Veritas)

An upbeat mood

As in past years, the CHDI meeting moved me profoundly.

I identified with the many difficult feelings and experiences recounted by Astri and Svein Olaf.

Once again, the scientists’ presentations reminded me of HD’s devastation of the brain – and of my vulnerability as a carrier of the HD mutation.

But this was a very upbeat conference. I had never spoken before to Dr. Tabrizi, but we hugged as if we were old friends after I congratulated her on the initial clinical trial report. The HD community has waited so long for such news!

Later, after I worked late into the evening on this article and missed the buffet dinner, Jerry Turner, the CHDI staffer in charge of conference logistics, arranged for a care plate of sumptuous leftovers from the kitchen of the Parker hotel, the gracious host of the conference.

I toasted to the success of the Ionis clinical trial and to CHDI’s commitment to the project with Doug Macdonald, Ph.D., CHDI’s director of drug discovery and development and its point man on gene-silencing.

As I told another scientist, I look forward to the day when we can all toast the discovery of an effective treatment.

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

The little things that are really big: caregiving in families with Huntington’s disease

The everyday kindness of the back roads more than makes up for the agony of the headlines – Charles Kuralt

As a member of a Huntington’s disease family, I have become deeply familiar with the common yet often unheralded human practice of caregiving.

My “HD warrior” father Paul Serbin cared for my HD-stricken mother Carol for more than a decade.

My mother died ten years ago this week. Her passing sent me into a months-long dual spiral of anxiety and depression: I had inherited the HD gene from her, and seeing her demise provided a portent of my own future (click here to read more).

Because of the inevitability of HD onset, I know that I too will require caregiving.

Furthermore, as a father, I’ve spent the past fifteen years helping my wife Regina raise our daughter Bianca, a special form of caregiving. Bianca tested negative in the womb, thus avoiding the specter of juvenile Huntington’s. As we teach her to drive and begin discussions about college, our role as parents becomes both more rewarding yet more complex.

Three weeks ago, the balance shifted, as Bianca and I became temporary caregivers for Regina: she underwent an operation to repair a torn rotator cuff and must keep her right arm in a sling for at least six weeks.

Completely interdependent

Caregiving is about all of the little – but really big – things we humans do for each other.

It’s how families, hospitals, and nursing homes run.

We are completely interdependent.

As we’ve helped Regina over the past several weeks, the meaning of caregiving has become ever more clear to me.

It involves small but important tasks: bathing her, spraying on deodorant, buttoning her shirt, adjusting her sling, driving her to doctor’s and physical therapy appointments, taking over her share of car pool duties, providing assistance in the kitchen, exercising her disabled arm – these and many more tasks have highlighted for me the importance of caregiving, taught me to be more sensitive to Regina’s needs, and reminded me of what’s most important in life.

Despite a busy high school life, Bianca has helped out, too.

It’s brought us closer together.

Bianca (left), Regina, and Kenneth Serbin (aka Gene Veritas) (photo by Bianca Serbin)

Valid and important emotions

I’m certainly no saint. I’ve done my share of grumbling! And sometimes I feel overwhelmed.

As I’ve learned from news items posted on Facebook HD discussion pages, caregiving experts say it’s okay to experience feelings associated with caregiving such as anger, boredom, frustration, and impatience.

“Whether you become a caregiver gradually or all of sudden due to a crisis, or whether you are a caregiver willingly or by default, many emotions surface when you take on the job of caregiving,” a recent article at Dementia Today states. “Some of these feelings happen right away and some don’t surface until you have been caregiving for awhile. Whatever your situation, it is important to remember that you, too, are important. All of your emotions, good and bad, about caregiving are not only allowed, but valid and important.”

As another article suggests, caregivers need to face emotions directly, find healthy ways to release anger, share feelings with close friends, and take breaks to pursue enjoyment.

These recommendations can apply to short-term caregiving situations such as recovery from an operation but also to long-term situations involving HD, Alzheimer’s disease, and other afflictions.

Overlooked and undervalued

Until my mother went into a nursing home in the final months of her life, my father cared for my mother’s daily needs with the assistance of a professional caregiver who visited their home a few hours each week. He helped her in the bathroom, fed her, and pushed her wheelchair.

She was the love of his life. He was stubborn about accepting more help at home and getting her physical therapy, but each day he climbed with her into the HD trenches.

Not once did I hear him complain. Maybe he should have!

In our celebritocracy, such dedication goes unrecognized. Each year family caregivers are estimated to provide the equivalent of nearly half a trillion dollars in unpaid care.

In America, care and caregiving are “overlooked and undervalued,” writes Zachary White, Ph.D., the author of the blog The Unprepared Caregiver.

Unlike highly valued, professional jobs, informal caregiving isn’t considered a career.

“Parents and relatives and friends won’t be able to brag about your experiences.” Dr. White writes. “There are no ‘schools’ of informal caregiving – no Harvard or Stanford to use as a guiding goal from which others can respect and admire. Others may speak highly of your role and your efforts, but it begins and ends there.”

While taking care of loved ones, members of the HD and other neurological disease communities have long advocated for better caregiver assistance and nursing home care – including disease-specific instruction for health aides. These will remain daunting challenges for the foreseeable future.

Preemptive caregiving

I believe that Regina’s devotion to me and our family is a big reason why I’ve passed my mother’s age of HD onset. She helps provide for the family by working as a full-time elementary school teacher; she sees to it that Bianca and I eat healthily; and she supports my HD advocacy.

She has done a lot of preemptive caregiving.

Caring for Regina during her recovery and remembering my mother’s struggles with Huntington’s have led me to reflect on my future caregiving needs.

As I race against the genetic clock and await the development of treatments for this incurable disorder and a health care system more responsive to those with brain diseases, I want to avoid becoming a burden on my family.

By maintaining good health in the present, I can perhaps reduce that future burden.

However, I know that, for each HD family, this is uncharted territory. We can forge ahead by caring for our our family members – and for the larger community.