Fear of onset: the inescapable reality of the Huntington’s disease gene carrier

As a carrier of the devastating and ultimately deadly genetic mutation for Huntington’s disease, I have worked hard to live as normally as possible. This blog is replete with examples of coping strategies and ways in which I have strived to balance work, leisure, family, and HD advocacy.

At 54, my HD-stricken mother was rapidly declining, heading towards a troubling and terrible death at the age of 68. Today, at 54, I continue to enjoy the gift of good health – the major reason I can often feel “normal.” Scientists are searching to discover the reasons for the wide variability in the age of onset observed in people, like my mother and me, who have the same level of mutation.

Yet my fear of onset often creeps back in.

Recalling a time of innocence

The past few weeks I’ve been so busy with the “normal” that I’ve had no time to write in this blog.

At work, I’m transitioning from five-and-a-half years as departmental chair to a year-long sabbatical, during which I aim to write a long-gestating book on the history of former Brazilian radicals now in positions of power. I’m also teaching an intensive, three-week summer session course on the history of Mexico. The next year promises to be an engaging, challenging time.

The transition has required an understandably disruptive move to a new office, but also allowed me to dispose of unneeded books and papers.

As I rummaged through old files and letters, I found myself reminiscing about the seemingly innocent period of my life before Huntington’s struck my mother.

It would be great, I thought, not to have to worry about onset. Without the threat of HD, which led me to expand my scholarly endeavors into the history of science, technology, and medicine, I could once again focus exclusively on the history of Brazil.

Watching for early symptoms

I’m also working out the logistics for my upcoming trip to the University of Iowa in Iowa City for my follow-up participation in PREDICT-HD.

An “observational study of the earliest signs of Huntington’s disease,” PREDICT-HD has aimed at creating key standards for predicting onset and measuring the rate of disease progression.

I’ll be staring onset in the face – and wondering about my performance on the battery of tests.

A visit to Auspex

I discussed my fear of onset and reiterated our community’s urgent need for effective treatments in an intense, 80-minute get-acquainted conversation last week with Pratik Shah, Ph.D., the president and CEO of Auspex Pharmaceuticals.

An investor-funded San Diego firm focused exclusively on central nervous system disorders and orphan diseases, Auspex struck me as made-to-order for the fight against HD. It is currently conducting clinical trials for a drug called SD-809, aimed at treating chorea, the involuntary abnormal movements produced by HD.

SD-809 (dutetrabenazine) is a potentially improved version of tetrabenazine, a chorea treatment currently marketed by the pharmaceutical company Lundbeck under the name Xenazine. If SD-809 works as intended, it will require fewer dosages and produce fewer side effects than tetrabenazine.

However, tetrabenazine does not affect the root causes of HD, nor is SD-809 expected to.

Auspex seeks to use SD-809 as a platform to research and develop drugs that would attack those causes.

Dr. Shah and I agreed to schedule soon an interview so that I can write an in-depth article on Auspex’s efforts.

I told Dr. Shah about a middle-aged, HD-afflicted man I had met who had maintained much of his cognitive abilities but suffered from strong chorea. However, tetrabenazine controlled the chorea, enabling him to keep driving, something most HD patients have to give up.

Tetrabenazine’s approval by the Food and Drug Administration had come too late to benefit my mother, who died of HD in 2006. I told Dr. Shah that she had taken another medication to control her chorea, which was relatively mild, although she had initially had strong chorea in her legs at night. In general, chorea was the least of my mother’s problems with HD, which devastated her cognitive abilities and caused serious psychiatric difficulties.

I also related my recent conversation with a former HD support group colleague who has had symptoms for a number of years.

Speaking to a symptomatic individual, I pointed out, provides me a terrifying glimpse of my own future.

A powerful HD dream

As I processed these latest events in my journey with HD, my unconscious mind produced a powerful dream.

I awoke from the dream at 5 o’clock on Sunday morning. Afraid that I would forget its content, I went to my home office to type out the details on my computer, and to outline this article.

In the dream, where I am meeting with other asymptomatic HD gene carriers, I encountered the same HD-affected man whom I had mentioned to Dr. Shah.

The people in our dreams often represent aspects of ourselves. In my interpretation, thinking of a symptomatic man in the context of a group for the asymptomatic meant that I was wrestling with the inevitable reality of my onset.

Tapping into the soul

As the dream continues, I fly to New York City on HD advocacy business.

In my hotel room, I start to write a blog article describing the recent HD-related aspects of my life. I have my trusty laptop with me but am oblivious to it. Instead, I write in longhand on a white legal pad. It’s the way I sometimes wrote in college or now write on airplanes or when I’m revising a draft I’ve printed out.

There’s something pure and primal about this form of writing. It’s the way I first learned to write. I’m crossing things out, jotting down ideas, and flipping back and forth through the pages to read and make adjustments. At one point I think that, because I don’t have much time before my evening HD meetings, I’ll switch to the computer. But I want to first eke out some more lines on the pad.

The dream was compelling me to practice the craft I have enjoyed since childhood, to tap into the soul that defines me.

I later recalled the photograph that an HD-affected man posted of himself illustrating his superb kickboxing skills before the disease struck. He wanted to remember himself at the height of his powers.

The dream, I think, reflected my fear that HD will rob me of my writing skills.

A metaphor for facing HD

Later in the dream, I go to a restaurant along with two other asymptomatic gene carriers and my friend, blog editor, and HD alter ego, Norman. One of the gene carriers, I recognize, is the symptomatic man I’d encountered earlier in the dream, only transformed into a healthy individual. On the way there, I give each gene-positive man a bear hug. I feel deep brotherly love towards these men.

A native New Yorker, Norman describes the restaurant as a very different and unique place. He says it’s called Pub Med.

We seem to be on the Upper West Side of Manhattan. Evening is approaching.

The restaurant is made of recently hewn, unpainted pieces of wood, which are also used as furniture: benches and small, round tables. It’s outdoors, located in the middle of a square where I can hear kids playing on swings and moms walking their kids. There are small stores on the edges of the square, too.

But there’s something very strange: the benches and tables are stacked on top of one another in a pyramid-like fashion. They rise about 30 feet. We climb up and look for a place to sit. Norman is sitting with the first gene-positive person while, at another table, the second gene carrier continues to explain to me the nature of this restaurant-structure and how to sit on it without falling.

I'm still standing. However, as I try to sit down, some of the tables and benches near me shift down or fall off suddenly and unpredictably. I’m afraid that I’ll fall off. The second gene carrier seems to know well how to deal with it. He’s experienced and seems to take it all in stride.

As I strive to keep my balance on the structure, I gaze at a different kind of Manhattan skyline. On the horizon, I see some burning buildings. Referring to the restaurant-structure and the buildings ablaze in the distance, I tell the second gene carrier: “I can think of no better metaphor to describe living at risk for Huntington’s disease.”

Building hope, pondering onset

The dream, I think, represented my fight to continue advocating for the HD cause.

Manhattan is headquarters for three key HD organizations: the CHDI Foundation, Inc., the Hereditary Disease Foundation, and the Huntington’s Disease Society of America. Along with other organizations and scientists around the world, they hold the key to finding treatments.

Norman has taken my family and me on a walking tour of Manhattan. He urged me to start this blog. In both the dream and real life, he has acted as a kind of guardian angel in my fight against HD. I believe that the Norman of the dream also symbolizes my own internal editor, who, like the real-life Norman, the author of a richly detailed and public-spirited watchdog blog on Brooklyn's Atlantic Yards project, strives to produce in-depth and understandable reports.

Along those lines, I had told Dr. Shah I would read scientific articles about SD-809 before our planned interview. I believe that the Pub Med restaurant represents my desire to prepare thoroughly for an interview regarding the potentially life-saving work done at Auspex. In reality, PubMed, a well-known research tool, has more than 23 million citations from biomedical literature, life science journals, and online books.

I explained to Dr. Shah that in this blog I seek to provide the HD community with information about potential treatments, breakthroughs, and challenges.

My goal is to provide the community with hope, and advocate for change.

The dream, I believe, also reflected my continued striving for internal equilibrium as I ponder the kind of onset I will experience.

Will I falter like an HD person who can no longer control movements and mind? Will I continue to work and drive? Will I be able to help support my daughter as she studies in college? Will effective treatments arrive in time to at least reduce the severity of symptoms – and prolong my life?

These are the inescapable questions of my reality as a Huntington’s disease gene carrier.

No time for complacency: get ready for HD clinical trials

In the past few years, scientists have made huge strides towards treating and perhaps even controlling Huntington’s disease, whose killer gene inhabits every cell of my body. While scientists scrupulously avoid providing false hope, even the most pessimistic among them now talk of “when” a treatment or treatments will come, not “if,” as international HD spokesperson Charles Sabine observed last October at the annual Huntington’s Study Group conference in San Diego, CA.

That’s enormous progress, compared to a decade ago, when practically no pharmaceutical companies showed interest in HD.

But this is no time for complacency. On the contrary, as labs ramp up for potential clinical trials to test the first group of the 700-plus potential “drug targets” for HD, many daunting challenges and tasks remain.

I plan to deliver this message in a speech this coming Saturday, July 30, at the 2011 Inaugural Clinical Research Symposium of the Northwest Chapter of the Huntington’s Disease Society of America (HDSA) at Evergreen Hospital Medical Center in Seattle, WA (click here for the program). The speech will be titled “What HD Families Should Know about Clinical Trials: Initial Thoughts from a Gene-Positive Activist.”

The clinical trial administrators will need a large number of symptomatic people to participate, ranging from 20 to as many as a couple thousand people per drug. With only 30,000 people in the entire U.S. affected by HD, it may prove impossible to fill the numerous spots in the trials.

That is why CHDI Foundation, Inc., the so-called “cure Huntington’s disease initiative,” has inaugurated Enroll-HD, the first-ever worldwide database of at-risk, gene-positive, and HD-affected people, in order to expand the base of possible trial participants.

All must chip in

As advocates like Charles and me have pointed out, those active in organizations such as the Huntington’s Disease Society of America (HDSA) can no longer limit our focus to fund-raising. At-risk, gene-positive, and affected people must also collaborate with the researchers and physicians in the process of planning and implementing the trials.

Preparing for potential trials requires that we care for our health as much as possible.

And, as I wrote in 2009, the untested in our community, who constitute a majority of the at-risk, need to muster the courage to learn their status. With the hope of treatments, refusing testing makes less and less sense. And, if people don’t get tested, they can’t participate in a trial.

In short, if we all don’t chip in, treatments won’t be found.

The painful barrier of denial

Chances are, if you read this blog, you already agree with this outlook. You’re probably active in the HD effort in some way. So, as they say, I’m preaching to the choir.

We need to reach out to those in the community who shun involvement, usually out of fear, and sometimes out of ignorance.

I know all too painfully how denial works.

My mother Carol died of HD in 2006 after battling HD for nearly two decades. Her at-risk, untested brother and his wife hid the truth about her disease from their children and their families by attributing Mom’s symptoms to “mental problems.”

A split family

I am also estranged from my own sister, the untested mother of three at-risk, untested adult sons whom she conceived before my mother’s diagnosis. She prefers to do nothing, because she does not believe, or is unaware, that there is hope. She is completely uninterested in advocacy, research, and trials.

As a gene-positive activist, I personify the knife-edge of HD for my family. My sister became especially uncooperative after the birth of our “miracle baby,” who tested negative in the womb. My sister was jealous for two reasons: we had a daughter, and she was HD-free.

In reading this description of my own family, many will knowingly nod in agreement. Denial is powerful, and it is everywhere. Combined with the sorrow, frustration, anger, and fear provoked by HD, it splits families apart.

I have fought back against the threat of HD by participating in numerous observational trials and advocating for the cause.

But I have yet to figure out a way to involve family members so deeply in denial – and so angry at me whenever I raised the issue of HD, directly or indirectly.

Living by example

As Charles observed, it will be truly tragic if people are not ready for clinical trials.

But we must not give up. Through this blog and my activism I have met many people new to HD and looking for ways to help. We need to welcome these individuals and their families with the greatest of attention – and love.

And we must live by example, because, in the end, our actions will carry far more weight than our words.

Defining success together

The HD community also can participate actively in the clinical trial process by helping researchers, physicians, drug makers, and the federal Food and Drug Administration (FDA) define a successful drug and how to measure that success.

HD causes a triad of symptoms: motor (shaking known as chorea and problems with coordination), cognitive (memory and mental abilities), and psychiatric (emotional disturbances). For a long time, scientists have spoken of the need for a “cocktail” of drugs to combat the triad and their numerous causes in the brain and brain cells.

So far, only one HD drug – tetrabenazine – has received FDA approval. Marketed by Lundbeck as Xenazine, this medication reduces chorea but does not affect the causes of HD.

The new generation of drug targets would indeed attack the causes. Researchers and drug makers theorize and hope that these targets would improve or perhaps even eliminate particular symptoms, but many of these new kinds of drugs represent uncharted scientific territory. Until the trials get underway, nobody will know how patients will respond.

So, even before trials start, patients must help define specific outcomes for the trials.

Maintaining functionality and personality

During the question-and-answer session after my May 17, 2011, speech at Alnylam Pharmaceuticals, I outlined what I thought were signs of success.

“From my standpoint, wow, maybe I will never have symptoms of Huntington’s disease,” I said in reflecting on the proposed Alnylam RNA interference drug, intended to attack the disease at its genetic roots and possibly ready for a Phase I trial as early as 2012. “That would be my hope as a patient.

“For the longest time, it’s like, ‘Well, you’re going to get sick.’ The question is: ‘When are you going to get sick? And how sick are you going to get? And what can you take to stop it?’…

That response came from my individual perspective as a gene-positive, asymptomatic individual – what the scientists refer to as the “presymptomatic” stage of HD.

But I also gave my opinion as to what symptomatic HD patients might want from a drug. I thought of my mother, who had been reduced to a “mere shadow of herself.”

We need drugs that will help people maintain their “basic functionality” and personalities. A bit of chorea would probably be acceptable as long as a person retains his or her mind and can go to work, I said.

“People want to keep their personality with this disease,” I said. “They want to be recognized as individuals. They don’t want to be seen as sick; they don’t want to be seen as drunk; they don’t want to be seen as disabled individuals.”

But I’m just one voice. More people need to give their opinions on this still very open question.

Strengthening the patient-researcher bond

As is often the case, I have only just scratched the surface of one of the many issues surrounding Huntington’s disease.

It’s clear that we all need to educate ourselves about the kinds of medicines under consideration and how they might affect the disease.

I hope to do my small part at the Seattle symposium. Across the country, our community needs more events such as this.

But in addition to speaking, I want to brainstorm with the audience about the definition of pharmaceutical success and absorb the other speakers’ ideas about clinical trials.

The HD community has a long reputation as one in which patients and researchers collaborate effectively. Now, as we get ready for historic clinical trials, we need to further strengthen that crucial bond.