A new attitude about Huntington’s disease

The words come like a slap in the face: I already have Huntington’s disease.

Even though I do not yet have the classic, overt symptoms of the disease such as shaking limbs, slurred speech, and decreased mental capacity, the fact that I inherited the genetic defect for HD from my mother means that my brain cells have already been compromised.

This is the new way that Huntington’s disease must be seen by patients, physicians, researchers, and public agencies, according to Robi Blumenstein, the president of CHDI Management, Inc., the firm that carries out the CHDI Foundation’s quest for treatments and a cure. (CHDI once stood for “Cure Huntington’s Disease Initiative,” but today is simply the name of the two organizations.)

Advances in scientific understanding of HD – including its early, subtle signs – have wiped out the old paradigm of classifying individuals as gene-positive but asymptomatic. The symptoms are already there on the cellular level, even if they don’t seem to affect daily life.

I visited CHDI’s Los Angeles research office on July 20 to meet Robi, staff members, and several of the many full-time researchers who are focusing exclusively on designing potential drugs to combat Huntington’s.

(This is the first in a series of entries on CHDI that will focus on this drug-discovery organization and its potential pipeline of Huntington’s treatments. The many possibilities in that pipeline reflect how HD attacks cells and the brain on many fronts.)

Personal feelings and our cause

Robi, who has read my blog for years and always thought of me as “Gene Veritas,” met me in person for the first time. Although I did not think of myself any differently, I at first felt awkward because I could see that Robi was suddenly absorbing myriads of new information about a person he had known only through an online pseudonym.

I had a similarly unnerving feeling when Robi, in introducing me to others, stated right off that I was gene-positive. I had never been introduced as such, and I could feel my good old friend denial wanting to split off my “Gene Veritas” identity and kick it out of the room. By visiting CHDI, I was taking a definitive step towards being more open about my HD status and more public in advocating the cause to eradicate the disease.

These personal feelings transcended my own individual predicament. Robi and I immediately launched into a discussion about how the world sees HD and why it’s all-important to galvanize people – especially in the HD community itself – to join the cause. Fear, ignorance, denial, courage, dedication, and the plethora of other reactions of HD families all complicate the decision engage in HD activism.

Robi, CHDI, and others in the HD community worry that potential treatments could start flowing out of the pipeline, but a shortage of participants in clinical trials and the lack of imagination of some trial administrators could prevent new drugs from getting properly tested and ultimately approved. (I had written about this topic on July 14.)

Seeking to inspire people

How, we asked ourselves, could we inform the community that researchers’ new view of HD has redefined how the disease should be dealt with by affected families? What would inspire people to become more active?

CHDI itself has been somewhat of a mystery to the HD community, even though last year it had a budget of $80 million, making it by far the largest non-governmental concern working on treatments for HD. Focused purely on science and drug discovery, CHDI has quietly gone about its work with the support of a donor who, like so many of us in the HD community, prefers to remain anonymous.

But because of the need to engage with HD families, CHDI needs to communicate better, as does the traditional Huntington’s Disease Society of America (HDSA), in which I have been an activist since 1998.

Increased knowledge about HD and how to measure its early stages have opened up the possibility of new drugs, and this in turn requires new ways to measure these drugs’ impact. MRI scans, for example, can show major changes in the brain of HD people many years before the classic symptoms appear. Similarly, scientists believe that early stages of the disease affect the sense of smell and certain fine motor skills.

Time to change attitudes

The medical community used to tell gene-positive people to take good care of their general health and simply hope the symptoms would appear late in life. For these people life is a time bomb. Individuals like my own sister, who has not been tested for HD and is in deep denial about the disease, say there is nothing they should do because there are no treatments. (Click here to read more about my extended family’s reactions to Huntington’s disease.) In fact, most at-risk people refuse testing.

The new HD paradigm, however, will require a big shift in attitudes, if we are to be ready for the treatments that CHDI and others are aiming to produce.

Robi described a simple but extremely important example of a time-honored test neurologists use to check Huntington’s patients’ motor skills. At the direction of the doctor the patient taps his or her index finger and thumb together rapidly. Early on people with HD lose the ability to perform this function.

One or more potential drugs against HD might prevent the loss of this capability, with the drugs' effectiveness measured through this simple test. But, as Robi pointed out, people in the medical and research community with traditional views of drug development might dismiss a treatment for something so seemingly unimportant if they do not clearly understand its importance as an indicator of neurological damage.

Get thee to a clinic

Everybody in the HD community – both the tested and the untested – should visit one of the 22 HDSA Centers of Excellence or other neurological clinics to be examined on a regular basis and to participate in the long-term studies that track the impact of the disease. People also should learn about clinical trials in their area. Centers of Excellence are a good source of information, as is the website HD Trials.

It is also time for new attitudes about genetic testing. For too long, people have avoided testing, fearing a potential death sentence. HD families must see testing as a way to connect with the effort to treat the disease and find a cure.

When scientists discovered the HD gene in 1993, nobody could yet speak of a drug pipeline. Today that pipeline exists with a large number of so-called drug targets, potential ways of alleviating and perhaps even stopping the disease.

Tested individuals are an important piece of evidence in the HD puzzle – not only for this generation but the next. Rather than a burden, testing can be seen as a step toward contributing to the greater good and the reaffirmation of life.

Getting tested requires great courage. But everybody has the potential to stir up that courage.

Going public

HD families must become more public, at the very least within our community. I have attended dozens of local fundraisers and other events over the years. These events are for the benefit of our families and HD people. But how many HD people and their families actually attend? Very few!

It’s not easy to get out of the house while suffering from HD. I know it’s difficult, because I had to help my own mother, who died of HD in 2006 at the age of 68, get in and out of cars, wheelchairs, and bathroom stalls.

But it’s not impossible. Centers of Excellence, support groups, caregiver resource centers, and other agencies offer strategies for keeping HD people mobile. Families can also consult the many books on caregiving such as Lessons from the Ancients: A Humorously Helpful Guide for Caregiving, by veteran HDSA activist Jim Calhoun.

HD families should become involved in support groups, the governing boards of local chapters, fundraising, and advocacy.

HDSA is supporting House Bill 678, which would end the standard two-year waiting period for disabled HD people to receive government benefits (click here to read more about the bill). Ask your congressional representative to co-sponsor this bill.

People can also tell their stories to the local media, via blogs, and on the websites of local chapters and organizations such as the Huntington’s Disease Advocacy Center.

As one leading HD activist put it recently at an HDSA support group, if we won’t help ourselves and speak out, why should anybody else care about us?

HD families need to press the flesh more often – within the community and in public. As painful as it may be, we also need to remind family members who are in deep denial that they can make a difference.

Strength in numbers

My own feelings and experience parallel what has happened in the HD community since the discovery of the gene in 1993 and the resultant promise of treatments and a cure.

I have struggled to strike a balance between the need to build public awareness about HD and the impulse to remain anonymous and shield myself, my career, and my family from the terrible prejudices, job worries, and insurance nightmares that surround Huntington’s and other neurological diseases.

Now we in the HD community have reached a critical juncture. With the hope of treatments and a cure, the time has come to speak out and build strength in numbers.

Great reasons to be a guinea pig

Huntington’s disease is a 100-percent genetic condition, so, because I tested positive for this brain disorder, I have no control over its cause. I will develop symptoms. After receiving my test results ten years ago, I could have gone into a cocoon or committed suicide or lived in reckless abandon. Instead, I decided to control what I could.

I became active in all senses of the word: watching my health, raising awareness about HD, participating in the local support group, and, as an activist for the Huntington’s Disease Society of America (HDSA), doing my small part in the effort to find treatments and a cure.

I have also taken part in numerous experiments designed to bring scientists a clearer understanding of the disease. I basically have become a guinea pig in procedures that are often repetitive, tiring, and sometimes downright boring.

They can also be very intimidating, because they force me to focus on my medical situation when I’d rather be doing something else.

But these experiments are vitally important for preparing the way for effective clinical trials. To see if a potential treatment is working, researchers must have a baseline of information about HD symptoms, including the practically imperceptible early signs of the disease in gene-positive individuals like me.

In fact, because of a shortage of test subjects, Huntington’s clinicians have been sounding the alarm for the need for more at-risk and affected individuals to join the experiments and also current and upcoming clinical trials for potential drugs.

Dr. Martha Nance, the director of the HDSA Center of Excellence in Minneapolis, has noted in a recent article that the lack of willing research subjects will “delay the development of new treatments for HD.” Similarly, Dr. LaVonne Goodman, the founder and director of the Huntington’s Disease Drug Works program (HDDW), has written that clinical trials “will accomplish little if we don’t take the next steps to maximize participation” (click here to read Dr. Goodman's article).

Many experiments, much information

I began the experiments after learning in 1995 that my mother had Huntington’s. I gave blood to be screened for the genetic defect. At that time I took the first in a series of occasional batteries of neuropsychological tests, which involve memorizing words, comparing objects drawn on paper, distinguishing the names of colors from actual colors, and other kinds of mental exercises. I have also lain for hours in functional MRI machines that took images of my brain as I slept or as I played a kind of video game with my fingers.

Scientists have even established that gene-positive individuals will suffer changes in their sense of smell. Accordingly, I took part in an experiment where I spent a long time sampling and identifying different smells of small amounts of substances presented to me in tiny cups.

I have also responded to questionnaires for the National Research Roster for Huntington’s Disease Patients and Families, a three-decade-old study of HD families headquartered at the University of Indiana.

And I am a participant in HDDW. I take HDDW supplements every day (the sugar trehalose, coenzyme Q-10, Omega-3 fish oil pills, blueberry concentrate, and creatine) in the hopes of staving off symptoms. I am required to do a periodic battery of tests on my home computer, such as tapping keys and performing mental exercises similar to the neuropsychological tests described above. In effect, I’ve been participating in a clinical trial of a kind of HD cocktail.

Testing my balance

The importance of the experiments and the stresses involved weighed upon my mind on July 13 as I took part in yet another experimental session, this one at San Diego State University.

The experiment focused on my motor control – the ability to move in a coordinated manner and to maintain stability. I had participated in the first phase of this experiment a year ago, and this latest session aimed to see if there was any change in my situation. Like most of the other experiments, it was designed to see if I am showing any symptoms of the disease so early and so slight that only a machine or a computer can detect.

First, I had to listen to about 60 beeps on a speaker and tap one of my fingers on a sensor in synch with each beep. A computer recorded my reactions for the research assistant in charge of the experiment.

I knew the experiment would probably include a test of this kind, so I prepared carefully in the morning. I didn’t want to do my daily stretch but did anyway in order to be as limber as possible, thus allowing me to have good posture and maximum dexterity.

I sat before the two sensors – one for the right hand, the other for the left – like a sprinter the moment before the starting gun is fired in the 100-yard dash. At first I made mistakes and did not keep up the tapping after the beeps had stopped, as the instructions had required. By the end I was trying to anticipate the first beep in order to make my first tap at the same time.



Outsmarting Huntington’s

As in other experiments, I needed to prove to myself that I had no symptoms. I strived to match the machine’s impulses as closely as possible. And, I thought, if I do have symptoms, I wanted my brain to compensate for them with the total concentration and energy I was devoting to the experiment.

Like the man who uses his intelligence to control his schizophrenia in the film A Beautiful Mind, I want to believe that I can outsmart these machines and ultimately Huntington’s disease itself.

In the next room I stood on the platform of a device used to measure balance. The SMART Balance Master, made by NeuroCom International, Inc., consisted of foot plates and surrounding scenery that both moved. The research assistant strapped me into a safety harness that would catch me in case I fell. In various tests, with my eyes opened and closed, I had to maintain my balance as the computer recorded reactions through foot sensors.

A research assistant demonstrates use of the balancing device.

I kept my balance with little effort and without the need of the harness. But I thought of how terrifying an experience such a machine would present to a Huntingon’s disease patient such as my mother, who died of the disease in 2006. In the last few years of her life she fell a number of times, once breaking a wrist, another time suffering a large gash on her head that required several staples. She would have found it practically impossible to remain standing in this machine, even though the movements are quite manageable for the normal person, akin to jerking motions on an escalator.

I did not ask the research assistant if he had detected any subtle symptoms of HD in my tests. I was not interested in such information, preferring instead to think that I had easily passed.

I need to continue thinking of myself as an asymptomatic at-risk individual. To learn that symptoms had started might prove too devastating to me at this time.

A sense of accomplishment

I ended the experiments with a sense of relief. I had once again stared down Huntington’s disease and, at least as far as I can tell, came away the victor.

As I look back on the day and the many other experiments in which I have participated, I have a deep feeling of satisfaction at having contributed to the gathering of knowledge about the disease.

The discomfort of having to think about HD and my mother’s demise is an extremely small price to pay for helping prepare for the day when treatments could help me and thousands of other at-risk individuals avoid early symptoms.

By participating in experiments, I’ll also be keeping myself properly informed about treatments as they become ready.

Everybody can help

Testing centers urgently need more subjects to take part in their experiments and clinical trials. Everybody can help: patients, at-risk individuals, relatives, and friends. Even if you and your family are not affected by HD, you can encourage affected families to participate and help ease the burden by driving them to the testing centers or assisting in other ways. Please contact HDSA or your HDSA chapter or Center of Excellence to learn more.

Those of us touched by HD cannot change our genetic reality, but together we can help build the mass of knowledge that will help scientists select the right treatments and fine-tune them so that people of all levels of risk and disease can benefit.

A life-or-death walk into the future

On June 15, 2009, I walked again into the epicenter of what could be the first treatment for Huntington’s disease: the Isis Pharmaceuticals, Inc. research facility in Carlsbad, California.

It was like a walk into the future. I am gene-positive for Huntington’s, and Isis is seeking to make a drug that could save me from one of humanity’s cruelest diseases. My mother, who passed on the defective gene to me, died of the disease in February 2006 at 68, after struggling with the disease for about twenty years. (Click here to read about how I said good-bye to her.) This year I turn 50, the age at which she was already showing symptoms.

Will I someday take the Isis drug for HD? Or will I be doomed to end up unable to speak and in a wheelchair?

Those were some of my thoughts as I followed up my April 2008 visit, when I learned how Isis was aiming to create a “laser-guided missile” to attack Huntington’s. (Please click here to read my entry on that visit.)

Cautious optimism

I heard great news: the project is on schedule, and both Isis and the sponsor of the research, the CHDI Foundation, Inc., are optimistic that they will find a drug molecule by the end of this year. Human testing would begin in 2011.

Last year I brimmed with enthusiasm about Isis, but the project was only in its early stages. My optimism was justified: this year I sensed great confidence at Isis. (Please click here to see my detailed update on the project.)

However, I am also tempering my optimism with the knowledge that pharmaceutical research – even in the case of a brilliant, cutting-edge company such as Isis – is always a long-shot. Only one in ten drugs that enter human trials will ever make it to market.

Effective research requires time – a commodity in short supply for those of us racing against the clock. As Dr. Frank Bennett, the Isis senior vice president for research, pointed out, even if everything goes perfectly, it would still take at least ten years for the drug to be fine-tuned for use as a preventive measure in asymptomatic, gene-positive individuals like me.

Fighting for the cause

But I am not disheartened. On the contrary, I feel the same confidence as Dr. Bennett and the other people I spoke with at Isis such as Dr. Alejandro Lloret, who is fighting passionately to find the treatment. (Please click here to read my article about Dr. Lloret.)

I know that I too must fight – to raise awareness about Huntington’s disease and to help bring more support for our cause. Isis is deepening its commitment to research on other neurological diseases. With its unique technology it could start a revolution in the pharmaceutical industry. We HD activists need to educate the public about the potential benefits of Huntington’s research for all of humanity.

Above all, I’ve got to stay healthy until the possible Isis treatment for at-risk people comes online. No gene-positive person can know the exact moment symptoms will start. All we can do is take care of ourselves and keep hoping.

Part of good health is staying informed and remaining optimistic. It was a tremendous boost to shake the hands of the people working to stop HD, to hear their own optimism, and to see them at work in the lab. They care about people like me, and that gives me the energy I need to keep up the fight.