Monday, April 20, 2015

The Huntington’s disease community can’t afford to lose momentum

The Huntington’s disease community can’t afford to lose momentum in the quest for treatments for this incurable disorder.

As I noted in my last article, fatigue can set in for advocates and family members. This is understandable, given the tiring demands of caregiving, the frequent feelings of hopelessness in the face of the “devil of all diseases,” and the immense challenge faced by scientists – and the population needed to participate in drug trials – in devising revolutionary drugs that reach the brain and prevent its cells from dying.

Interrupting my own momentum in writing a book in my field as a Brazil specialist, I summoned the strength to once again focus on HD. I traveled coast-to-coast twice in a little more than 72 hours to give a speech about a crucial upcoming HD clinical trial and to interview a prominent scientist engaged in the search for treatments. It was an intense time.

My trip on April 10 began inauspiciously, as a late departure from San Diego caused us to approach Atlanta as thunderstorms struck, leading the flight to detour to Birmingham, AL. Arriving in Atlanta close to midnight, I had missed my connection to Providence. After finally finding a hotel 20 miles from the airport, I could only sleep four hours. The morning flight to Providence also left late, because of tardy pilots.

Travelers do face such stresses, especially as service in the airline industry declines, but as a carrier of the HD gene mutation concerned about disease onset, I especially need to avoid them.

As it became clear that I would miss my 9 a.m. keynote talk on April 11 in Norwich, CT, Laura Kokoska, an advocate for the Connecticut affiliate of the Huntington’s Disease Society of America (HDSA-CT) whose mother has HD, helped me via cell phone calls and texts to calmly consider alternatives. She and another advocate, Val Kim, whisked me from Providence to Norwich, serving me lunch in the car. We arrived in time for me to speak in the last slot of the day.

The audience of some 30 was anxious to hear me provide an HD family member’s perspective on one of the most significant steps towards treatments since the discovery of the huntingtin gene in 1993: the Roche/Isis gene-silencing trial, set to start this year at several sites in Canada, England, and Germany.


HDSA-CT education event participants (from left to right): James McGann, Debbie Pausig, Gene Veritas (aka Kenneth Serbin), Laura Kokoska, Holly Broadbent, and Sue McGann

A historic attack on the genetic roots

I first explained how my mother’s demise from HD and my positive test for the genetic mutation in 1999 led me to delve into the science of Huntington’s disease. Then I described how since early 2008 I have tracked the program by Isis Pharmaceuticals, Inc., to stop HD at its genetic roots. In 2013 Isis partnered with the pharmaceutical giant Roche to prepare for a gene-silencing clinical trial in HD.

“This trial is a historic trial,” I said. “It’s a big moment in the history of our community, and also in the history of science.”

Isis and Roche aim to test a drug known as an antisense oligonucleotide (ASO). “That’s a fancy term for basically saying it’s an artificial piece of DNA,” I continued. “That is [a] ‘laser-guided missile’ that is supposed to go into the brain cells, and it will block the production of the huntingtin RNA and the protein.[…] The protein is what is causing the problems in the cell. They’re also thinking now that the RNA is also causing problems within the cell, that they want to cut down the amount of the RNA, too.

“This clinical trial […] is the first time that someone is going after the genetic roots of the disease,” I stressed. “That is an immense motive for hope in our community.” And that’s why I’m so excited about the project and follow it so closely.

Being realistic

I showed PowerPoint slides of photos of the Isis facility and the company’s scientists, including Frank Bennett, Ph.D., the senior vice president for research and the head of the HD project. I also noted the important support for the project from CHDI Foundation, Inc., and the lab of Donald Cleveland, Ph.D., at the University of California, San Diego.

I reminded the audience that enthusiasm must be coupled with patience: the HD community must recognize the time it takes to develop drugs and also brace itself for failures in the quest for treatments. This year Isis and Roche are initiating Phase I of the trial, aiming only to test the safety and tolerability of the ASO.

Potential Phases II and III would examine the drug’s efficacy. In all, it could take five years or more to complete all three phases.

“We have to be realistic,” I said. “Ninety percent of drugs that go into clinical trials do not make it to market.[…] It takes a lot of shots on goal before you finally get a goal.[…] We have to keep in mind that it’s a slow, painstaking, and deliberate process.”

You can watch my speech in the video below.

Returning to Yale

After the event I rode to New Haven with Debbie Pausig, a marriage and family therapist, grief counselor, and HDSA-CT support group leader. Debbie recently published An AffaiR Worth Remembering With Huntington’s Disease: Incurable Love & Intimacy During an Incurable Illness, a memoir of her relationship with her late, HD-stricken husband. Debbie capitalized the “r” in “affair” – and it’s reversed on the cover of the actual book – to emphasize the many unusual twists in her story.

Later I visited the campus of Yale University, my alma mater, and ate pizza at an old haunt. It was only the fourth time I’ve returned to Yale since graduating with a B.A. in history in 1982. In 2012 I visited Yale to interview a number of scientists working on HD (click here to read more), including the preparation of clinical trials.

“Felt like an undergrad again walking through freezing campus,” I texted an old classmate while watching the students and remembering the exhilarating possibilities of youth.

In my hotel room, mixing in baking soda and Epsom salt from a care package put together by Laura, I relaxed in a hot bath. As Laura put it, the bath would help my body recover from the traumatic plane trip.


Gene Veritas (aka Kenneth Serbin) outside Wall Street Pizza (formerly Naples) in New Haven

A science tour and lunch with old friends

The next morning I took a tour Yale’s Magnetic Resonance Research Center with its long-time director, Doug Rothman, who received his Ph.D. from Yale in 1987. A professor of diagnostic radiology and biomedical engineering at the Yale School of Medicine, Dr. Rothman is one of the world’s leading pioneers in research in MRI, magnetic resonance spectroscopy, and quantitative neuroscience with magnetic resonance.

A future article will detail my interview with Dr. Rothman about his research into key questions about the mitochondria, the powerhouses of our cells, and their role in HD.

I lunched with classmate Paul Bass and his wife Carole (Yale 1983), two former colleagues on the Yale Daily News and accomplished journalists in New Haven. The Basses have long served as confidantes.  

Paul’s innovative online community newspaper, the New Haven Independent, was one of the first sites to link to this blog, and Carole blogged for the Yale Alumni Magazine about my definitive exit from the HD closet in 2012.

I welled with emotion at seeing my old friends, hearing good news about their lives and young adult daughters, and sharing my joy at having remained asymptomatic beyond my mother’s age of onset.


Paul and Carole Bass (photo by Gene Veritas)

Supporters of the HD cause

That evening in New York I dined with another Yale friend, Norman Oder (class of 1983), and his girlfriend Maryanne. A journalist, editor, and founder of the watchdog blog Atlantic Yards/Pacific Park Report, Norman urged me to start this blog and has edited virtually every piece since its inception ten years ago.

During my 24 hours in New York, Norman and I had several deep conversations about my future health, the destiny of this blog, and numerous aspects of the HD movement. He is my “HD alter ego.”

On April 13, I had lunch with yet another classmate, Adam Glick, a businessman and philanthropist who has generously supported the HD cause. Adam’s real estate company owns the Parker Palm Springs, the hotel in Palm Springs, CA, that expertly hosts the annual, CHDI-sponsored HD Therapeutics Conference when it takes place in the U.S.

I gave Adam a rundown of the 2015 conference, which I attended. We also discussed the “nocebo effect,” the idea that the expectation of illness can bring on symptoms even though a person is not ill.

I told Adam that last year two major supplements – coenzyme Q10 and creatine – thought to have potential for treating HD were proven ineffective. I speculated that my belief in these supplements’ efficacy might have contributed to my lack of symptoms.

Quiet resolve

At Maryanne’s suggestion, I visited the Museum of Modern Art (MOMA) to view the special exhibition of Jacob Lawrence’s series of paintings about the great migration of African-Americans from the rural South to the urban North in the mid-20th century.

This significant event in our nation’s history is forgotten by many. As a professional historian, I was both intrigued and moved by the tempera paintings depicting the hardships of African-Americans in the South and the brave decision by millions to uproot themselves to find a better life.

My teenage daughter, a first-year high school student, had asked me to take photos of murals in New York. I didn’t have time to search for murals, but Lawrence’s paintings are mural-like and tell a vast story. I will soon show them to her.

Visiting MOMA gave me a break from the HD-laden aspects of my trip. Yet I could not help but draw a parallel between the quiet resolve of the migrants and the yearning of the HD community for liberation from the yoke of Huntington’s disease.

Through such resolve we can maintain the momentum necessary for defeating HD.


The African-American South-North migration of the mid-20th century as depicted in one of the paintings of Jacob Lawrence (photo by Gene Veritas)

(I wish to thank the individuals and organizations that organized the conference and sponsored my trip: Sue McGann, HDSA-CT, and the Wireless Zone Foundation.)

(Disclosure: I hold a symbolic amount of Isis Pharmaceuticals stock.)

Tuesday, April 07, 2015

Engaging a ‘scared population’ of Huntington’s disease families by respecting their journeys

The number of clinical trials for Huntington’s disease treatments has increased exponentially, pushing up the demand for volunteers. Now advocates ask a pressing question: how to inspire more affected families and individuals to participate?

I have addressed this theme with increased frequency in recent years, as in my last two articles (click here and here to read more). As a carrier of the devastating HD mutation who saw his mother succumb to the disease, I feel in my gut the urgency to involve other members of the community.

“If no patients or gene-positive people show up for trial participation there will be no novel treatments, ever!” Daniel P. van Kammen, M.D., Ph.D., wrote in an e-mail in response to my articles.

For several years, I have maintained a dialogue on this topic with Dr. van Kammen, from 2007-2011 the chief medical officer for CHDI Foundation, Inc., the nonprofit virtual biotech focused exclusively on developing HD treatments. A professor emeritus at the University of Pittsburgh, Dr. van Kammen currently serves as an independent consultant for central nervous system (CNS) clinical trial development.

“The notion that if you build it they will show up, just does not work!” Dr. van Kammen continued. “In general only 5% of people diagnostically eligible for drug development study participation, do so. This is fine for a large population with Alzheimer’s. Not for the HD community either at risk or diagnosed. So people have to come forward.”

As he indicated, there’s a relatively small number of HD-affected individuals, estimated at 30,000 in the U.S. By contrast, as many as 5 million Americans over age 65 may have Alzheimer’s.

Beyond that, a good number of HD-affected individuals cannot participate in clinical trials because of so-called exclusion/inclusion criteria. (I’ll write about this issue more in a future article.) So that leaves an even smaller number of potential trial subjects.

The Enroll-HD program, the global platform, research project, and family registry aimed at facilitating clinical trials and the discovery of treatments, recently marked its 5,000th registrant but needs as many as 25,000 more volunteers.

People deciding at their own pace

Over my nearly two decades of advocacy – my mother was diagnosed in 1995 – I have learned that it’s important to respect the unique journey of each individual touched by HD. Without that respect, we cannot begin to engage what Dr. van Kammen described as a “scared population.”

From a pure research standpoint, the more at-risk people who test for the HD gene, the better. Despite the enormous psychological burden of knowing that I will develop HD, I don’t regret undergoing genetic testing.

I often wish that more individuals from the untested at-risk pool – the vast majority of those people don’t  get tested – would also test and/or participate in programs such as Enroll-HD, which doesn't require that people learn their genetic status.

But then I remember how I wanted to get tested immediately after learning of my mother’s diagnosis. I postponed the decision after receiving advice regarding the discriminatory consequences of testing, and, more than three years later, bit the genetic bullet because my wife and I wanted to know my status before starting a family. Six months later our daughter tested negative for HD in the womb.

What a journey!

When I meet people new to HD, I am aware that I can offer ample advice based on experience. However, I stick to the basics, allowing them to ask questions and share their stories and fears at their own pace. I remind myself that testing for HD is often an extremely trying process, with implications for the extended family. This personal decision requires time and reflection.

People new to HD are embarking on their own journeys based on their backgrounds and particular point in life.

The same respectful approach applies in encouraging people to attend a support group, visit the local HD clinic, participate in fundraising activities, and enrolling in studies and clinical trials.

The dynamics can be complex. In the face of HD, many families close ranks. However, many split, beset by fear, denial, and the stigma of HD.

Activists’ self-respect

I have received enormous respect from my fellow HD advocates.

We activists must always remember to respect our own journeys.

At 55, I have passed the age of my mother’s HD onset. Each day without symptoms is a gift.

To maintain self-respect, I must allay guilt about doing too little for the cause. I especially feel this way when missing a support group meeting or a local event of the Huntington’s Disease Society of America (HDSA).

Lately I have also faced advocacy fatigue. However, seeing other, often less fortunate families suffer from HD – like the young man holding his HD-stricken grandmother or the family with members stricken by both adult-onset HD and juvenile HD – leads me to gird myself again for the fight. On April 11, at an HDSA educational event at the William W. Backus Hospital in Norwich, CT, I will share my story and the hope offered by the upcoming gene-silencing clinical trial planned by Isis Pharmaceuticals, Inc., and Roche.

In re-engaging, I remind myself that my journey is unique, too, with my own particular moments and needs.

Enjoying the present, planning the future

Twenty years into the cause and ever closer to disease onset, I need to focus on my health, enjoying life, and my family.

With a sabbatical from teaching duties, I am also writing a long-gestating book on Brazilian politics that I had partially put aside because of my work as departmental chair the past five and a half years and my developing interest in the history of science, technology, and medicine.

As our daughter approaches college age and my wife and I initiate conversations about retirement plans, we are also focusing on shoring up the family finances. As all HD families know, losing a working family member to the disease not only severely reduces family income but also creates a caregiving burden very costly in both time and money.

Luckily neither of lost our jobs in the Great Recession, but like many Americans in the eroding middle class we have received little or no increase in income during the recovery.

At 55, I also face the normal challenges of aging. Over the past eight months I have struggled with a nagging elbow pain that has prevented me from swimming, my preferred exercise and excellent for cardiovascular and brain health. Luckily, with my doctor’s okay, I am back swimming, although the pain continues. Because of pain elsewhere in the body, I have spent many an hour at physical and occupational therapy sessions.

I want to remain as limber as possible to facilitate coping with HD symptoms (more on this in a future article).

I also continue to exercise my mind. As I wrote to an old friend regarding the recent tenth anniversary of this blog and its 200th article, “Writing for survival is my motto.”

Affirming the good in our lives

Like many others in the HD community, my journey has deepened my search for spiritual meaning.

I have added another book to my morning meditation, Gratitude Works!, a book about gratitude journaling by Robert A. Emmons.

Writing regularly about the positive experiences in our lives promotes a shift in awareness from “what we are lacking to the abundance that surrounds us,” Emmons writes.

“Gratitude leads us to affirm and acknowledge the good things in our lives,” he adds.

Our community has immense suffering, but is also has immense good.

I am grateful for remaining asymptomatic today, for the many people bravely struggling to come to terms with HD, and for the great respect the members of the HD community have for each other as we live our unique moments together.

I’ll be even more grateful when more people enroll in clinical trials. Yes, we may be a “scared population.” But we may also be a “sacred population,” one dedicated to a deeper purpose, helping to conquer this awful disease.

Tuesday, March 24, 2015

The precious participation of the Huntington’s disease community in the quest for treatments: a report on the 2015 HD Therapeutics Conference

As long-awaited clinical trials of new drug candidates for Huntington’s disease get underway, scientists have intensified collecting information from research study participants to quickly and accurately test the effectiveness of the potential remedies.

This was a major theme of the 10th Annual HD Therapeutics Conference, held February 23-26 at the Parker Palm Springs hotel in Palm Springs, CA. (Click here to read my initial report on science and solidarity, filed during the conference.)

The event was sponsored by CHDI Foundation, Inc., a nonprofit, virtual biotech focused solely on developing HD treatments and the largest source of private HD research funding. Backed by wealthy donors, CHDI has an annual budget of about $100 million.

“The thing that I’m keying on is what I would call human data,” Robert Pacifici, Ph.D., CHDI’s chief scientific officer, told me in an interview on February 26. “Obviously when we do drug discovery we think about a variety of model systems – everything from worms to flies to zebrafish to sheep and songbirds and everything in between.

“But we both know that the only organism that actually has Huntington’s disease unfortunately is the human. So for a long time I’ve been saying that there’s nothing more precious and valuable to a drug hunter than an observation that’s actually made in the population that they seek to treat, in our case Huntington’s patients.

Dr. Pacifici recalled how genetic data from hundreds of people from dozens of families led to the discovery of the huntingtin gene in 1993. Thanks to those efforts, treatments aimed at lowering the amount of mutant huntingtin RNA and protein in the brain cells of HD patients are on the verge of entering clinical trials, he added.

“Now what we’re asking for is to really start getting more specific about the observations [in humans] that we want to make and how we’re going to leverage them,” Dr. Pacifici explained.

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


Key role of modifier genes

Dr. Pacifici cited two major examples of new human data revealed at the conference that will a have profound impact on the quest for treatments.

“We’re literally at the precipice of identifying what are modifier genes,” he said, referring to the research presented by Jong-Min Lee, Ph.D., of Massachusetts General Hospital. “It’s just incredibly exciting to me.”

An abnormally expanded huntingtin gene is the principal cause of HD, but other so-called modifier genes also help determine the age of disease onset.

“Why is it that one person’s Huntington’s starts earlier than another?” Dr. Pacifici asked. “That’s tragic.” More positively, it also means the other person’s onset starts later. “Well, that’s exactly what we want a drug to do.”

Human data has played a major role, he pointed out. With thousands of HD-affected people participating, researchers have been able to examine their genetic composition, involving not just their Huntington’s gene, “but their entire genome, to do what’s called a Genome Wide Association Study, or GWAS, and figure out what it is that’s different about individuals that causes one person’s Huntington’s to start earlier than another,” Dr. Pacifici explained.

In his presentation titled “Medication of Huntington’s disease by genetic variations,” Dr. Lee reported how the large research team seeking modifier genes has narrowed its search to chromosomes 3, 8, and 15. (Located in all of a human’s cells, the 46 chromosomes are long, twined strands of DNA containing a person’s entire genetic heritage.) According to Dr. Lee, chromosome 15 has both a “bad” and “good” modifier, with a six-year difference in onset between individuals having one versus the other.

“If we can identify that [good] gene and figure out how it’s doing that, then what we have is a very specific set of instructions for drug hunters to make a compound that does that same thing,” Dr. Pacifici said.




Jong-Min Lee, Ph.D. (photo by Gene Veritas)

Cheating a little bit with biomarkers

The second example involves cerebrospinal fluid (CSF), the liquid that bathes the brain and circulates up and down the spine. Researchers have been searching for HD-related biomarkers in samples of CSF taken from volunteers afflicted with the disease as well as so-called premanifest people, individuals who (like me) carry the gene but have yet to show classic, easily notable symptoms such as involuntary movements (chorea and other types).

Dr. Pacifici defined biomarkers as “a way of cheating a little bit” to get signals without waiting for the more time-consuming and more expensive later phases of a clinical trial.

The human brain can only be studied directly only after a person has died, as pointed out in a talk on CSF by Ed Wild, M.D., Ph.D., of the University College of London. Imaging methods such as MRI are helpful but very limited. So scientists are putting ever greater emphasis on finding signals in the CSF such as mutant huntingtin protein and other biomarkers.

CSF provides a “snapshot of what’s going on in the human brain,” Dr. Pacifici observed, adding that it might indicate in a clinical trial whether a huntingtin-lowering drug is having the desired effect.

Clinical trial administrators would still need to wait many months to get meaningful observations about actual effects on symptoms, but seeing what the drug does at the molecular level is a key first step.

“In other words, we don’t want to give the drug [. . .] and hope that after three years of waiting that we’re going to have an effect,” he said. “We want to know right away that that drug was doing the job that it was charged to do, in this case lowering huntingtin levels.”

A CSF study

Describing the analysis of CSF from HD patients in a research study of twelve individuals that he helped direct, Dr. Wild observed that the closer a premanifest individual was to probable onset, the higher the level of mutant huntingtin found in the CSF. Similarly, among affected individuals higher levels of the mutant protein correlated with worse symptoms.

Dr. Wild and other scientists are still striving to determine the specific origin of the mutant huntingtin found in the CSF. At this point they hypothesize that it comes from neurons, a specific type of brain cell.

Scientists aim to improve CSF collection efforts and obtain a clearer understanding of what occurs in the CSF through a new, CHDI-funded project called HDClarity. The initial research sites are at University College of London, the University of British Columbia, and the University of Ulm, Germany.

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


The rise of clinical trials

The need for clinical trial volunteers will increase dramatically as the number of trials grows rapidly.

With a total of nine active trials, 2014 had an “unprecedented amount of activity in clinical trials in Huntington’s disease,” Ray Dorsey, M.D., a professor of medicine at the University of Rochester and the president of the Huntington Study Group, stated in an overview of recent HD trials.

These trials included the two largest-ever regarding HD: a study of coenzyme Q10 with 609 participants and a study of creatine with 553 participants. Both were halted because of lack of efficacy, but helped scientists understand the need for better evaluation of substances before taking them into a trial, Dr. Dorsey noted.

Last year brought one of the few successes in HD clinical trial history: the highly favorable results of Auspex Pharmaceuticals’ testing of its compound SD-809, which reduces chorea substantially and with fewer and milder side effects than its predecessor drug, tetrabenazine.

Presenting a chart of clinical trial trends, Dr. Dorsey demonstrated that the number of HD trials is growing exponentially: from four trials in 1999-2002 to 28 trials in the period 2011-2014.

“I think we’re poised for success,” he concluded.


10th Annual HD Therapeutics Conference participants watch a presentation (photo by Gene Veritas)

Assessing the potential of gene-silencing

In reviewing the clinical trial outlook for 2015, CHDI’s consulting medical director, Bernhard Landwehrmeyer, M.D., Ph.D., noted the continued upward trend, with six active trials.

Dr. Landwehrmeyer described the plans for a Phase I gene-silencing clinical trial by Isis Pharmaceuticals, Inc., and Roche. This approach seeks to attack the causes of the disease at its roots (click here to read more).

Isis’s senior vice president for research, Frank Bennett, Ph.D., stated in his conference presentation that the trial would begin by the end of the second quarter, but Dr. Landwehrmeyer predicted it would start later in the year. It is only the very first step in gene-silencing treatments for HD, he stressed.

Nevertheless, he observed that many other companies and labs are working on their own versions of gene-silencing treatments for HD. The chart he displayed showed 14 other entities in addition to Roche and Isis.

“It’s important that we have such a rich toolbox in attempts to make gene-silencing a therapeutic reality,” Dr. Landwehrmeyer said.

He noted that the Isis/Roche trial is unusual because it must include symptomatic patients, who will receive the gene-silencing drug via a spinal tap. Typically a Phase I trial accepts only healthy volunteers because it is testing for safety and tolerability, not for efficacy.

The trial will take place at HD centers in England, Canada, and Germany that have in-patient intensive care monitoring facilities, he noted.

Dr. Landwehrmeyer said it was important to set realistic expectations for the HD community, which anxiously awaits good news about gene-silencing because of its potential to significantly impact the disease.

“You are NOT missing the boat, if you do not participate in the Isis study,” he said, referring to HD-affected individuals. Establishing safe and effective gene-silencing therapies for HD will still take “decades.

Once trials prove them to be safe and effective, these drugs can reach the market and become available to all HD families.


Bernhard Landwehrmeyer, M.D., Ph.D. (photo by Gene Veritas)

Big challenges remain

Dr. Landwehrmeyer also commented on the other trials taking place this year: Pride-HD (to test pridopidine); APACHE and Amaryllis (to test “Viagra for the brain”); LEGATO-HD (to test laquinimod); and a forthcoming trial in deep brain stimulation.

In all, he noted, at least 1,500 HD patients are expected to take part in clinical trials this year.

“That’s on the one hand fantastic,” he said. “But timely recruitment into these studies has become an issue.”

Some HD study centers are underutilized, while others are overloaded, he noted. The number of trial participants is further restricted by inclusion/exclusion criteria (for example, the particular disease stage of the patient). Pharmaceutical companies should enhance a “culture of cooperation” regarding trials, he said, and regional and national patient advocacy organizations need to activate their networks.

Enroll-HD, the global platform, research project, and family registry aimed at facilitating clinical trials and the discovery of treatments, recently reached a milestone with its 5,000th registrant, but needs to grow to as many as 30,000, Dr. Landwehrmeyer observed.

Hoping for an end to conferences and HD

The 10th Annual HD Therapeutics Conference had numerous other compelling presentations on the search for treatments. Click here to visit my video album, where you can view many of the presentations.

The conference also featured some 90 posters detailing cutting-edge HD research projects.


Conference attendees view posters of Huntington's disease research projects (photo by Gene Veritas)

“Obviously we’re a time-motivated organization, and we know patients are waiting,” Dr. Pacifici said. “So the fact that it’s taken us ten years to get to this stage is not necessarily something to celebrate. That said, I think we should pay homage to the progress that’s been made over that period of time.”

Dr. Pacifici observed that with well-designed clinical trials, “it’s really an exciting time” in the quest for treatments.

He said that he was struck by the courage and collaborative spirit of the community, from academia to the private sector to the families. He also thanked HD families and their supporters for their participation in research studies, clinical trials, and other activities.

“This isn’t a competition,” he declared. “This is an opportunity for all of us to enable each other, which I don’t take for granted, because one of the potential downsides of getting to the endgame – which we are – is that’s when people start to be a little more secretive and a little bit more protective. We saw here time and again even multinational pharmaceutical and biotech companies standing up at our conference and presenting new, unpublished findings so that everybody could benefit from them.”

Along the way, failures will occur, because drug discovery is a very inefficient process, he emphasized. (Only one in ten clinical trials results in a marketable drug.)

“That’s frustrating,” he recognized. “Don’t be disheartened. Know that we have a large and deep portfolio [and] that we’re going to learn from each one of these failures. I think, and I have every confidence, that we’re going to start getting real positive signals that then we can build on. And that’s when the fun starts.

I hope we’re sitting here together again next year for the eleventh conference, but I also hope we’re not sitting down here for too many more. And I mean that in a positive way.”

* * *

For additional coverage of the conference, visit HDBuzz.net.

(Disclosure: I hold a small number of shares of stock in Isis Pharmaceuticals, Inc.)

Thursday, February 26, 2015

‘None of us are free until we are all free’: science and solidarity at the 10th Annual Huntington’s Disease Therapeutics Conference


Riding the emotion of a keynote speech by a young scientist at risk for Huntington’s disease, and seeking treatments with the immense help of a non-profit foundation, the participants at a historic research conference this week witnessed the fusion of science and human solidarity ultimately necessary for defeating HD.

On the evening of February 23, I and the approximately 300 attendees at the 10th Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc., listened as Jeff Carroll, Ph.D., recounted his mother’s demise from HD, his positive test for the HD genetic mutation, and his decision to pursue a career in science to save himself and others from HD.

“He’s an interesting combination of things in terms of being an advocate in the community, in terms of being someone from an HD family, in terms of being a top-flight researcher in the HD community, in terms of being a great communicator – he and his partner Ed Wild – in establishing HDBuzz, which is just a tremendously useful model of how to communicate results out to the rest of the community,” Robert Pacifici, Ph.D., CHDI’s chief scientific officer, said in introducing Dr. Carroll at the conference in Palm Springs, CA.

As an HD researcher-advocate who has attended all ten therapeutics conferences since 2006, Dr. Carroll offered a uniquely qualified, candid assessment of the progress towards treatments and CHDI’s role in the process.

“Every year, I come home revitalized and energized by the site of so many smart people working so hard on this problem,” Dr. Carroll, 37, told the audience in the main ballroom at the Parker Palm Springs hotel. He expressed his profound gratitude to CHDI, which has funded his and numerous other scientists’ research.

Painful progress toward success

However, success depends on the “efficient and timely completion of well-designed Phase III trials with HD drugs,” Dr. Carroll continued.

“A few weeks ago I attended a meeting at the Princeton CHDI office that included attendees from major pharmaceutical companies currently running HD clinical trials,” he said. “They are deeply concerned about something that would never have occurred to me to worry about, which is poor recruitment for trials of Huntington’s disease drugs.

“On reflection, it makes sense that the HD community may be wary of the way we have been speaking to them. Participating in the first clinical trial of a new molecule might be exciting, but participants of the third could be excused for having some questions.”

Trial administrators put participants through a daunting number of tests, he observed, which may discourage people from participating in more than one trial. Because trials are extremely expensive, sponsors often try to maximize the findings in Phase II, but not enough trials are reaching Phase III, he added.

“It must be said the scale of what is possible here must be unique in human history,” Dr. Carroll said of the efforts by CHDI, which has put more than $700 million towards treatments. “Resources on the scale being deployed by CHDI have been spent on common diseases, but never before have they been spent on such a focused attempt to ameliorate a rare disease.”

The HD community will achieve “something never done before” or “fail majestically,” he quipped with irony.

He added: “We might actually be watching the painful progress toward success.”

You can watch Dr. Carroll’s speech in the video below.


Our brothers and sisters

After Dr. Carroll and his wife Meghan had HD-free twins, thanks to preimplantation genetic diagnosis (PGD), he believed that “HD is done killing people in my family until I am gone,” he recalled.

However, recently two at-risk babies were born in his extended family.

“For a brief window, my family was the last that had to face this awful threat,” Dr. Carroll said. “But the arrival of these children has reminded me that none of us are free until we are all free.”

We must “raise up those of our brothers and sisters still suffering,” he concluded.

Like me, Dr. Carroll is racing against the genetic clock.

Crying for our community

This conference, my fifth, has proved especially poignant for me personally – even more so than the 2011 meeting, which I keynoted. In terms of the quest for HD treatments, it has been a landmark event. (My next article will provide an overview of the conference’s scientific aspects.)

I was both deeply saddened and heartened by Dr. Carroll’s story. I relived my own mother’s death from HD in 2006, my positive test for the gene in 1999, and my daughter’s negative test for HD in the womb (PGD was unavailable) in 2000.

It was one of the best speeches I have heard in two decades of observing the HD movement. Dr. Carroll tempered his enthusiasm and compassion for the HD community with hard-nosed, no-nonsense scientific analysis.

For the evening of February 25, the conference organizers arranged for a surprise outdoor screening of the 28-minute documentary The Lion’s Mouth Opens, about actress, director, and producer Marianna Palka’s positive test for HD. The film made the 2015 Academy Awards shortlist for Best Documentary Short.

As part of the surprise, Marianna, whom I had met earlier in the day, took questions from the audience. She appeared at the edge of the crowd, next to me, just as the film was ending.


Gene Veritas (left, aka Kenneth P. Serbin), Marianna Palka, and Louise Vetter, CEO of the Huntington's Disease Society of America (photo by Jerry Turner, CHDI)

It was a highly emotional experience for me. Filled with anger, frustration, and overwhelming sadness that a young person like Marianna should have to face HD, and once again reliving the trauma of my own HD test and the excruciating experience of testing our daughter, I hugged Marianna and cried uncontrollably for several minutes as she held and consoled me.

It’s so unjust that people have to face HD, I thought to myself.

I hardly ever let myself think that, trying to be strong, but at that moment I allowed myself to do so, and also to let loose all of the powerful emotions of the conference.

I told Marianna I was so sorry for her.

Marianna, who is just 33, was strong, telling me that we would all work together against HD.

After the film finished, Marianna talked with the audience about her experience of genetic testing, her strategies for staying healthy, and her work in film. She observed that The Lion’s Mouth Opens makes men cry.

You can watch Marianna’s exchange with the audience in the video below.


Enrolling families in the fight

At the start of the conference, I had lunched with Joe Giuliano, the CHDI director of clinical operations in Princeton, N.J., HD advocate Jimmy Pollard, and Chris Brown, a scientist from Evotec, a drug discovery company headquartered in Germany.

We pondered the same critical issue raised by Dr. Carroll, and that brave advocates like Marianna impel us to consider: how to inspire more families in the HD community to become involved in research studies and clinical trials.

I recalled my own speeches and blog articles about the terrible barriers to greater involvement: ignorance, fear, denial, stigma, and family tensions.

Giuliano is also the chief CHDI administrator for the Enroll-HD program, a global platform, research project, and HD patient and family registry aimed at facilitating clinical trials and the discovery of treatments. As Giulano and others have noted, it is not scientists who cure diseases, but the patients who participate in clinical trials.

That observation provides a fitting coda to Dr. Carroll’s speech.

And it underscores the absolute necessity to fuse science and solidarity in the fight against not just HD, but all diseases.

For an update on Enroll-HD, watch my interview with Giuliano below.


A personal landmark, and gratitude

With this article I have completed my own HD milestone: it is the 200th post in this blog.

I am grateful to so many: God, my wife and daughter, my HD-victimized mother Carol Serbin, my HD-warrior father Paul Serbin, who died with a broken heart in 2009, CHDI, and the entire HD community.

Although I worry that my overly emotional response to the conference could signal the mood swings characteristic of early HD onset, I am also grateful that I remain, according to my last neurological checkup, asymptomatic.

As I prepared to depart the conference, I pondered how the HD movement can reinforce human solidarity and our bond with the researchers.