The search for Huntington's disease treatments is indeed ‘rocket science’ – and we can all help build the rocket

For people facing Huntington’s disease and other devastating, untreatable conditions, the powerful wish for a cure can conjure up the image of an elated scientist bursting from a laboratory and declaring “Eureka!”

However, it is unlikely a treatment for HD will emerge in this way.

We often misunderstand scientific progress, as explained in an essay in the May 16, 2015, edition of The New York Times by prominent physicist Leonard Mlodinow, Ph.D.

“Why do we reduce great discoveries to epiphany myths?” asked the sub-headline for Dr. Mlodinow’s online article, which was titled “It Is, in Fact, Rocket Science.”

“The mythical stories we tell about our heroes are always more romantic and often more palatable than the truth,” Dr. Mlodinow writes. “But in science, at least, they are destructive, in that they promote false conceptions of the evolution of scientific thought.”

From Isaac Newton to Charles Darwin to Stephen Hawking, we have oversimplified the process of discovery, Dr. Mlodinow explains. Rather than the eureka moments popularized in books and the media – like the apple falling on Newton’s head – these scientists’ discoveries involved years of hard work and questioning of assumptions, including their own.

Thus, Dr. Mlodinow reminds us that breakthroughs result from the cumulative build-up of many moments of discovery by scientists past and present.

He thus underscores a crucial point for the Huntington’s disease community: finding treatments will necessarily involve a collective effort by scientists and volunteers in research studies and clinical trials.

“Even if we are not scientists, every day we are challenged to make judgments and decisions about technical matters like vaccinations, financial investments, diet supplements and, of course, global warming,” Dr. Mlodinow points out. “The myths can seduce one into believing there is an easier path, one that doesn’t require such hard work.”

We in the HD community must all play our part in the quest for treatments.

A eureka moment deflated

As a carrier of the deadly HD mutation who watched his mother succumb to the disease, I have sometimes fallen prey to the seductive scenario described by Dr. Mlodinow, and even done so in this blog.

Four years ago this month, I was so excited about Alnylam Pharmaceuticals’ progress towards a remedy that I posted a picture of myself holding an Alnylam compound designed to attack HD at its genetic roots. I wrote that the compound, “the potential cure in my hand,” seemed magical.

I later made the image my Facebook profile photo.

(See the photo below and click here to read more.)

Gene Veritas holding the Alnylam compound in 2011 (photo by Dr. Matthias Kretschmer, Alnylam)

I had perhaps become overconfident about the Alnylam project.

In collaboration with its partners Medtronic and CHDI Foundation, Inc., the nonprofit virtual biotech focused on HD treatments, Alnylam was planning to apply in 2012 for permission to start a clinical trial.

In early 2012, however, Alnylam cut a third of its work force in order to reduce costs. In May of that year, less than a year after my 2011 visit, the company shifted its business strategy. It downgraded the HD project and fired the scientific director in charge

Alnylam chose instead to concentrate on less complex – and perhaps more profitable – projects to find drugs for other conditions. Alnylam passed on the responsibility for testing the compound in a human clinical trial to Medtronic.

To date, Medtronic has announced no plans for a human clinical trial of the Alnylam compound.

“Medtronic believes the siRNA [gene-silencing] drug-device program continues to represent an exciting opportunity to combine an innovative therapeutic strategy with state-of-the-art drug device delivery technology for Huntington’s disease,” Jack Lemmon, Ph.D., a Medtronic program manager, responded in an e-mail to my request for an update on the project. “Pre-clinical work has generated promising results; however the therapy research program has been paused since 2013 until partnerships can be established allowing us to sustain the research. At this time, it is premature to discuss timeframes, but we hope to continue work to find a treatment for this devastating neurodegenerative disease.”

Shots on goal

I am concerned that the project runs the risk of entering a not uncommon limbo, which one former director of the National Institutes of Health calls the “valley of death,” the increasingly difficult transition between laboratories and clinical trials.

Devising the Alnylam compound involved a significant investment of time, money, and expertise. In my extensive interviews with Alnylam scientists in 2011, and even in a conference call with some of those same researchers after the announcement of the 2012 cutback, they expressed enthusiasm about the promise of the compound.

The Alnylam compound may – or may not – ultimately play a role in the search for treatments.

Without the Alnylam compound, the HD community would have one less shot on goal in the critical gene-silencing field.

I am disappointed at the lack of action – much less progress – regarding the Alnylam compound.

Fortunately for the HD community, one of those shots is scheduled to take place this year: Isis Pharmaceuticals, Inc., and Roche will start a historic gene-silencing clinical trial using a different type of drug technology. Other companies and labs are also focusing on the development of gene-silencing approaches for HD.

The Alnylam project didn’t meet the expectations of many in the community. However, it has still provided valuable data from which other researchers can benefit. I am grateful for Alnylam’s contributions to the quest for treatments, and I’m crossing my fingers that Medtronic can resume the project.

I indeed recognize that the path to treatments is not easy. Nor is it straight.

One example of a potentially fortuitous outcome of the Alnylam decision: the dismissed HD project director, Dinah Sah, Ph.D., now works as the senior vice president of neuroscience for Voyager Therapeutics, one of the new companies exploring gene-silencing for HD.

Dinah Sah, Ph.D., of Voyager Therapeutics (photo by Gene Veritas)

A road paved with cooperation

Enthusiasm is essential, but it must be tempered with the recognition that scientists need time – and money – to test hypotheses.

It took some two decades to discover the huntingtin gene. At the time of this breakthrough in 1993, people in the HD community celebrated.

Rightfully so, hope for treatments increased significantly.

Since then, hundreds of researchers from around the globe have published thousands of scientific papers on HD. Along the way they have identified hundreds of potential HD drug targets (biological pathways).

From the 1970s until today, thousands of individuals from HD-affected families have participated in research studies and, more recently, a growing number of clinical trials.

While many of us are disappointed that successful treatments have not emerged, we must recognize that the enormous amount of scientific work regarding HD should contribute – perhaps in ways no one yet knows – to future progress.

The road to treatments is paved with cooperation, and with the recognition that multiple drugs may be needed to manage this complex genetic disorder. (Thus, scientists don’t say “cure” when referring to HD.)

Cooperation: the HD community out in force at an HDSA Team Hope Walk (photo by Gene Veritas)

Something larger than ourselves

Our society worships individual “heroes.”

However, in the fight to defeat HD, each participant contributes with his or her talents and resources: financial donations, scientific expertise, caregiving, and daily dedication to the cause.

In this long-term commitment, we strive for the well-being of those beyond ourselves: the children who have yet to develop symptoms, the future generations of HD families, and other disease communities such as Alzheimer’s, Parkinson’s, and many conditions even rarer than HD like dentatorubral-pallidoluysian atrophy, known as DRPLA.

For now, I’ll keep my Facebook profile photo as a symbol of hope governed by caution.

Yes, defeating HD is rocket science. When, collectively, we have completed that rocket, we can all ride it together.

(Please remember during HD Awareness Month to donate generously to the Huntington’s Disease Society of America or the HD cause of your choice!)

Seven years of striving for a realistic and unapologetic view of Huntington’s disease

This week marks the seventh anniversary of this blog.

On January 10, 2005, I inaugurated the blog with this sentence: “My name is Gene Veritas and I am at risk for Huntington’s disease.” The article was titled “Huntington’s disease: an early date with mortality.” I adopted a pseudonym – the “truth in my genes” – to protect my family’s privacy, avoid genetic discrimination, and express myself freely.

I wasn’t sure where the blog would go, but since then I have written a total of 118 articles, exploring in depth the many facets of HD.

Baring my soul

I have bared my soul about HD. I have chronicled my mother’s downfall and my devastation after her death, my father’s dedication as her “HD warrior” caregiver, and my conversations with my daughter about HD as she moved from early childhood into the pre-teen years. I inherited the HD gene from my mother but, as my wife and I thank God, did not pass it on to our “miracle baby.”

I also have tried to document the completely new, little-known, and harrowing human experience of living in the gray zone between a genetic test result and disease onset. Along those lines, At Risk for Huntington’s Disease has served as both a coping mechanism and method of advocacy. I have written frequently about my fears – and of my frenetic activity in the effort to defeat HD. For me it provides catharsis – and a stimulus to my brain in the hopes of staving off HD’s inevitable symptoms.

For a community desperate for good news, I have strived to make At Risk a beacon of hope. I have reported from the frontiers of science in articles about research conferences and potential treatments such as the effort by Alnylam Pharmaceuticals to devise a drug to stop HD at its genetic roots.

And the blog has helped me to exit the terrible and lonely “HD closet,” where I long hid because of fear of genetic discrimination. In February 2011, I gave the keynote address at the “Super Bowl” of HD research, the sixth annual HD Therapeutics Conference of the CHDI Foundation, Inc. (CHDI,backed by wealthy, anonymous donors, is the so-called “cure HD initiative.”) I posted a video of the speech in the blog. Since then I have written about other public speeches and posted videos from them.

Valuable lessons

I also have explored the many lessons gained from my fight. I have learned to put life in a broader perspective, to pay greater attention to my family, and to value the preciousness of time. Like Michael J. Fox, I consider myself a “lucky man” because of the richer life I have lived.

In At Risk, I have confronted the deep challenge to my Catholic faith posed by the threat of HD. That threat led me to explore the spiritual dimensions of my struggle, and it has strengthened my faith and expanded my understanding of life’s purpose. I embrace a new kind of faith – not one of passive acceptance of one’s condition but of active transformation of the world.

The threat of HD and my role as blogger have given me an important mission: to stop the suffering caused by brain diseases.

Difficult truths

The more I have enmeshed myself in the far-flung HD community, the more I feel the urgency of my mission.

When I write, I feel raw anxiety as I am forced to contemplate my gene-positive predicament. I share that anxiety with many in our community as they struggle with symptoms or worry about onset. The lack of an effective treatment, much less a cure, further deepens our collective fear, pushing many people into the closet and away from the research studies and clinical trials necessary for finding solutions.

Indeed, because of the harrowing nature of this existence, I often feel as if the articles somehow write themselves – as if a mysterious, hidden hand were assigning me each topic and guiding my fingers across my computer keyboard.

At Risk has stirred emotions and shed light on difficult truths in a community where silence and stigma are too often the rule.

This past year was especially intense. I wrote 33 articles, and my audience grew as I expanded my blog e-mail list and increased my number of Facebook friends to more than 2,000. In June the Huntington’s Disease Society of America named me its 2011 HDSA Person of the Year for my advocacy and blogging efforts.

In 2011, I focused on such difficult topics as HD and dating, conflict and competition within and among the various HD organizations, and the need to combat complacency to generate enough volunteers for the upcoming clinical trials.

My article about the media and the astronomical rate of suicide in the HD community prompted one activist to request that I stop posting links to my blog on a Facebook page for young people and HD.

While my training as a journalist and a historian might have prompted a response emphasizing free speech – why should someone else deny others information? – HD has a way of challenging any belief in absolutes. I agreed to let the activist serve as a gatekeeper for that Facebook page and to decide whether to post my articles.

Challenging absolutes: HD and abortion

Just last month, the issue of absolutes was tested in a way many readers found personal, and painful.

I tackled – as fairly as I could – the issue of HD and abortion, examining the cases of two families, one opting for genetic testing and termination, the other forgoing testing and deciding to carry the pregnancy to term.

Interviewing the families and writing the articles presented one of my most difficult challenges in nearly 14 years as an HD advocate. Hearing their stories stirred up sad memories of the horrible weeks of worrying and wondering as my wife and I awaited the results of our daughter’s HD test in early 2000.

I received a record number of comments on the blog as well as numerous comments on Facebook.

Some commentators described the first family as “murderers.”

“I think that posting this article glorifying the killing of a baby is irresponsible of you,” wrote one commentator who opposes abortion and hadn’t slept for two nights after reading the first article. “You are a powerful voice in our community, and I am disappointed in your blog, especially around the holiday season…. It is sad that a family who kills their baby because it has the gene for HD is glorified.”

Others warned against passing judgment, urging compassion for families facing such terrible choices.

“I really absolutely admire your bravery in exposing this disease in a realistic and unapologetic way,” wrote Stella, another gene-positive blogger, in response to the same article. “As for this family, I wish I could just hug them all.”

Combating stigma (again)

My articles led Dr. LaVonne Goodman, the founder of Huntington’s Disease Drug Works and physician to several dozen HD patients, to write a scientifically informed article on “choice and reproductive decision-making in HD.”

In this balanced piece, Dr. Goodman referred to the deep controversy raised by my articles and once again raised the crucial question of stigma and its stifling impact on HD families.

“Those who are affected by identifiable genetic disease like HD suffer not just from societal and intra-family stigma – but also from internalized stigma that we have ‘learned’ from others, and incorporated into self,” Dr. Goodman wrote. “Often internalized stigma has great negative impact on HD individuals and families…. How many decisions are made because we hate aspects of ourselves – not just the disease?

“The goal is to make life worth living: No one should answer for another whether life was, is, or will be worth living [just] because HD gets bad for a long time at the end. Instead all of us, our HD institutions, our organization, and our families should put more energy into improving treatment and care for those with HD, so that lives become more worth living. And we should work to identify, describe, and decrease HD stigma – which adds so much burden for all in HD families. And in regard to helping with reproductive decisions we should work to provide non-discriminatory support and easier voluntary access to PGD [pre-implantation genetic diagnosis] with attention to supporting the emotional and financial costs involved in this procedure.”

No need to apologize

I often wonder: how many tragic stories do we never hear because of people’s inability or unwillingness to exit the HD closet?

Indeed, because of understandable but unfortunate feelings of stigma, our community often seems timid and even apologetic – precisely the attitude that we can and should combat. Everyone can contribute to this effort – by participating in a support group, joining the local HDSA chapter or affiliate, or volunteering at fundraising events.

No one should apologize for having HD, living at risk, caring for an HD person, questioning the scientific and organizational status quo, or raising awareness!

We all rely on denial to get over the daily fear of HD, but ultimately we must compartmentalize denial and confront the truth of our existence.

No one need hide the hard reality of HD. It is a fact of our lives – and a crucial event in the quest to control neurological disorders and improve the overall health of the brain.

The next seven-year cycle

In popular wisdom, life proceeds in seven-year cycles.

Seven years ago, I fully expected that by now – age 52 and the time of onset of my mother – to have symptoms and be unable to write. I have been extremely lucky in remaining asymptomatic.

I fervently hope to proceed through my next seven-year cycle without symptoms. Until a treatment is found, this can only mean an even deeper commitment to the cause – but also to enjoying the healthy moments, the blessing of each symptom-free day.

During this new cycle, my daughter will grow into a young woman and prepare to head off to college.

Will I stave off HD in order to help her reach her goal and watch her enjoy her own life?

Or, in a darker scenario, will she become my caregiver and perhaps even shoulder the task of writing occasional updates to this blog?

These kinds of questions will haunt my days as I await news of a treatment.

No matter what the outcome, I will proceed as unapologetically as ever.

Striving for brave new brains

As I turned 52 on December 31 and a new year dawned on the world, I came ever closer to onset of Huntington’s disease, the cruel killer that took my mother’s life in 2006 at the age of just 68.

However, in 2012 I also will live with the hope that, as science and medicine progress with time, researchers will control and perhaps even eradicate HD.

Indeed, we stand on the verge of a new age. Neuroscience, brain scans, our understanding of genetics, and brain-machine interfaces will vastly improve the health and capabilities of the brain and perhaps enable the cure of HD, Alzheimer’s, Parkinson’s, Lou Gehrig’s, stroke, and numerous other maladies of the central nervous system.

On Christmas and my birthday I was able to celebrate the results of my annual check-up at the local HD clinic on December 20: the doctor marveled at how, despite carrying the same genetic defect as my mother, I have yet to show any apparent external symptoms of the disease (click here and here to read about my HD-avoidance strategies).

With the predicted biotechnological advances, those of us who are gene-positive may someday put bionic brains on our birthday wish lists – brains without risk of HD and that enhance mental capabilities far beyond anything we can currently imagine. Even sooner, advances in medicine may deliver drugs and techniques that counteract the cruel changes wrought in HD brains.

Breathtaking predictions

I contemplated these possibilities during my holiday reading, which included Judith Horstman’s The Scientific American Brave New Brain: How Neuroscience, Brain-Machine Interfaces, Psychopharmacology, Epigenetics, the Internet, and Our Own Minds Are Stimulating and Enhancing the Future of Mental Power, an exciting, easy-to-read synopsis of recent advances in brain science.

Horstman outlines how brain scientists predict breathtaking breakthroughs by mid-century – most with a firm foot in current reality.

According to scientific forecasters, “computer chips or mini-processors in the brain will expand memory; control symptoms of brain disease, from Parkinson’s disease to depression and anxiety; and wirelessly receive and transmit information so that you won’t need a cell phone or a computer to stay in touch.”

“Brain surgery will be a thing of the past except in the most severe cases,” Horstman continues. “Advanced neuroimaging will identify mental illness and brain disease before symptoms show and in general be used to ‘read’ minds and predict and control behavior. Microscopic robots – nanobots – will enter your bloodstream to diagnose and repair brain damage. Protein molecules will travel your brain in a similar way to turn on or off brain cells or genes responsible for brain diseases.”

Brave New Brain explores numerous other current and potential facets of brain health and related technologies, including:

● neurogenesis (the growth of new brain cells);

● deep brain stimulation and “brain pacemakers” (using electricity to stimulate brain health and performance);

● brain-nurturing mental and physical practices such as meditation, breathing, and yoga;

● the impact of digital technology on the brain and its integration into the brain;

● artificial intelligence;

● miniature cameras for broadcasting images of the inner workings of the brain;

● thought-activated neural implants (for example, for working mechanical limbs);

● prostheses of portions of the brain (people are already living with artificial retinas and cochleas, the auditory portion of the inner ear);

● and, in one forecaster’s view, the downloading of our brains onto chips “so our consciousness can live on forever, perhaps even downloaded into robots – or into an avatar, an ageless biological clone,” perhaps making us an endangered species increasingly replaced by cyborgs.

“Neuroethicists” and others worry that “humans will become machines,” Horstman observes. These individuals also point out new issues involving privacy in genetic testing; ownership of body parts, tissues, and genes; insurance discrimination; potential abuse of new technologies by employers and others; and the impact of all of these changes on social equality and our way of controlling criminals. Neuroethicists are grappling with these many issues.

Curing dementia

According to Horstman, Alzheimer’s, other dementias, and perhaps even mental retardation will be “preventable, curable, and even reversible in many people.”

The demand for cures is immense: some two billion people worldwide suffer from a brain-related illness, with an annual economic cost of more than $2 trillion, Horstman writes. Almost half of all people over age 85 develop dementia, and by 2050 an estimated 100 million individuals will experience this condition.

Offering a glimpse of how these cures could take place, Horstman writes of “brain boggling” nanotechnologies such as “preparing specialized protein molecules that swim to a predetermined site and are activated externally by probes or lasers that turn off or on specific genes.”

This kind of “nanomedicine” would allow medical treatments to leap across the formidable blood-brain barrier, which separates the bloodstream from the fluid that bathes and cushions our brains, Horstman explains.

Alnylam’s HD gene-silencing trial

The trends in neuroscience and related fields mean that scientists someday will likely control HD and perhaps, as Horstman describes, completely turn off the gene that causes it.

Key research in “gene silencing” already holds great promise.

In partnership with Medtronic, in 2012 Alnylam Pharmaceuticals plans to apply to the federal Food and Drug Administration (FDA) to conduct a Phase I clinical trial of a drug containing ALN-HTT, a small interfering RNA molecule (siRNA) that doctors will inject into the brains of trial participants.

Conducting a brain operation, doctors will run thin tubing under the skin from a Medtronic-designed pump to a nodule at the top of the patients’ heads, and from that point a very fine needle will deliver the drug into the putamen, one of the regions of the brain most devastated by HD (click here to read more).

If the Phase I trial demonstrates the safety of ALN-HTT, Alynlam will proceed to Phase II to measure the efficacy of the drug.

Alnylam intends to use ALN-HTT to silence the huntingtin gene so that less huntingtin protein is produced to harm brain cells. If successful, the treatment would save brain cells from dying and slow down and possibly even reverse the course of HD.

A decade ago, this approach seemed like science fiction. Today, it provides immense hope that HD will be controlled in our lifetimes.

On December 28, 2011, Alnylam presented a highly positive report: testing of ALN-HTT in non-human primates demonstrated “widespread distribution of the siRNA and significant silencing of the huntingtin mRNA.” The drug was well tolerated.

Conducted in collaboration with Medtronic and a research team at the University of Kentucky, the study will greatly facilitate the FDA application for a human trial.

Isis Pharmaceuticals, Inc. is developing a similar approach for treating HD and hopes to apply for its own Phase I clinical trial, perhaps within the next year or two (click here to read more).

The pioneering HD community

As Horstman describes, such gene silencing techniques only scratch the surface of the great potential in brain-disease treatments. Indeed, we may someday look back on these initial attempts as primitive.

But they are revolutionary. We in the HD community are helping to pioneer this revolution in brain science by participating in research studies and clinical trials, fighting the terrible stigma associated with the disease, and, as I did last February, exiting the terrible “HD closet” to tell the world about the need to defeat HD and other neurological disorders.

HD families no longer stand alone. Our movement has gone global – with international conferences run by research organizations, numerous HD-related websites, and the establishment of Enroll-HD, a multi-country database of HD-affected, gene-positive, and untested at-risk individuals. Just last month a new HD group formed in China, the world’s most populous country.

We stand on the frontier of science, and for this reason in 2012 and beyond we can forge ahead proudly and bravely.

It’s up to us to lead the way. If we all unite and participate in this great movement, we can help build toward the bionic brains of the future.

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.

Face to face at the Huntington's disease convention

I’ve known about Huntington’s disease ever since my mother’s diagnosis in 1995. For just about as long, I’ve been affiliated with the Huntington’s Disease Society of America (HDSA). I joined the HDSA-San Diego support group in 1996 and served on the chapter board from 1998 to 2010. Last month I visited HDSA national headquarters in New York, where I gave an informal talk to the staff about my struggles as a person who is gene-positive for the disease.

Still, work and travel commitments have prevented me from ever participating in the organization’s annual convention.

That’s about to change this coming Thursday, June 23, as I travel to Minneapolis for the 26th annual convention, held at the Sheraton Bloomington Hotel.

A record 1,000-plus registered individuals are expected to attend. I am looking forward to meeting people from other HD-affected families, brainstorming on how to strengthen our cause, and sitting in on several workshops and other activities scheduled for the June 24-25 agenda. Among others, these include explanations of the disease, caregiving issues, advocacy, and a major session on the latest research developments. (Click here for a complete list.)

It should also prove highly rewarding – and hopefully plain fun, also! – to solidify some of the many online friendships I have developed over the years through this blog and my presence on Facebook.

A pivotal year

I’m bracing myself emotionally for what should be a very poignant experience.

In June I normally visit Brazil to conduct research as a professional historian. However, for the first time in a quarter century, I am skipping my annual visit to the country that is my second home and the birthplace of my wife. (She and our HD-free ten-year-old daughter arrived in Rio de Janeiro last Saturday after we spent a short vacation together in Florida visiting the Harry Potter theme park at Universal Orlando.)

This leaves me sad and reminds me once more of how HD has stolen many of our dreams as a family.

It also symbolizes the big shift in my life as I more carefully focus my efforts to help scientists in their quest for treatments and a cure.

In that respect, this year has become pivotal. On February 7 I delivered the keynote address to some 250 scientists, physicians, pharmaceutical company representatives, and others at the 6th Annual HD Therapeutics Conference in Palm Springs, CA, on February 7. On May 17 I gave a similar presentation to about 50 scientists at Alnylam Pharmaceuticals in Cambridge, MA, and held a sample of the company’s potential drug in my hand.

At the HDSA convention on June 25 I’ll take part in the traditional candle service, where representatives of the community light candles for the various groups within the HD community. My candle will represent “the hope of people living with HD.”

For me, this will be a great moment of solidarity. I will also be thinking of my mother, who died of HD in February 2006.

I know, too, that I’ll probably see scores of HD people – each one a reminder of my future as I await the inevitable onset of symptoms that characterizes HD.

Is a convention necessary?

Echoing the critical remark I read on Facebook yesterday, some might question the wisdom of holding a convention when so many HD families are in dire need. Attending a convention is beyond their means financially and/or logistically. They need help in the HD trenches.

Indeed, last month I wrote a blog article titled “S.O.S. for Huntington’s disease families." The article discussed the loss of income and extremely burdensome caregiving costs faced by these families. The demand for assistance far exceeds what HDSA can provide with its $8 million annual budget.

HD families should always question the goals and activities of the organization. Indeed, they are the organization. Only in this manner can our organization improve.

Over the years I have attended conventions and meetings of various kinds for professional or other reasons. Conventions are only as good as the people who attend and the ideas they contribute.

I am looking forward to the HDSA convention, because, in addition to the reasons I outlined above, it will provide me with the opportunity to meet people face-to-face, to see their body language, to build trust and camaraderie, and to exchange ideas freely.

I believe that this kind of contact can reinforce teamwork and strengthen our movement. Hopefully it can also bolster our hearts and souls.

As always, I’ll have my camera, voice recorder, and camcorder in hand to capture some of the highlights of the convention, and I’ll be blogging on the results upon my return.

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Speaking of conventions, it’s time to sign up for the World Congress on Huntington’s Disease, to be held in Melbourne, Australia, from September 11-14. Interested scientists and members of the HD community can obtain more information about this all-important event by clicking here.

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In my last article, “The Huntington’s disease high-wire act,” I neglected to mention that a book with a similar title, On a High Wire, Without a Net! Living with Huntington’s Disease was published in 2009 by HD activist and writer Susan E. Lawrence. Susan also wrote Sheltered from the Storm: Preparing for the HD Onset. Both books are valuable resources for our community.

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This is my 101st posting in this blog! I began At Risk for Huntington’s Disease in January 2005. Let us all hope that sometime within the next 100 postings we can celebrate a major breakthrough towards a treatment for HD.

The Huntington's disease high-wire act

As a carrier of the gene for a deadly brain disease, I fight back with the instinctual urge for survival.

I dread the threat of that incurable killer – Huntington’s disease – as I recall my mother’s own struggle against it. For some 15 years, as I watched her lose the ability to walk, talk, and think, I looked into a genetic mirror that foretold my own future.

In the months before and especially after her passing in February 2006, I grappled with the fear of death. For the first time in my life, I knew I would die, and that death would come only after a decade or more of suffering. I am reminded of that harrowing reality each time I see an HD person or communicate with HD-affected families.

I also nurture hope that scientists will discover an effective treatment – perhaps even a cure – and therefore make my gene-positive status at best irrelevant and at worst a manageable, chronic condition, like diabetes. In the meantime, I watch my health and take supplements recommended by the Huntington’s Disease Drug Works program, try to squeeze in as much life as possible before my inevitable symptoms begin, and immerse myself ever more in my “shadow career” as a Huntington’s disease advocate.

In this race against time, I oscillate between dread and hope while struggling to balance the many facets of my life: profession, family, health, faith, and activism.

Tough decisions

“So many tough decision and choices,” wrote a good friend after reading about my shadow career. “You are like a tightrope walker, like the ‘Man on a Wire.’ Did you ever see that wonderful film? I recommend it – because living with a positive gene test as you are, balancing so many things, is a bit like what he does.

“And like him, you are an artist with a beautiful, amazing sense of living in the moment even while looking ahead.”

I was long intrigued by the theme of Man on Wire but hesitated to watch it, perhaps fearing that it would indeed remind me too much of living gene-positive for HD. Last Sunday, June 5, I finally watched it.

In walking on a wire between the World Trade Center’s Twin Towers in 1974, French aerialist Philippe Petit demonstrated how he lived out his ultimate fantasy joyfully – but also precariously, tempting mortality.

I know many people in the HD community performing their own, tragic tightrope acts – like the young adults pondering whether to test, couples debating the genetic risks of pregnancy, and caregivers weighing the decision to place a loved one in a nursing home.

Whereas Petit chose to risk his life on the wire for 30 minutes and had to be coaxed off of it by the police, HD people and their families are forced onto the wire and cannot get off. Although many still find moments of joy, all long for the treatment or cure that will end this ultimately nightmarish act.

Passion vs. obsession

My own personal tightrope includes yet another kind of balancing act: between passion and obsession.

Since joining the San Diego chapter of the Huntington’s Disease Society of America (HDSA-San Diego) shortly after my mother’s 1995 diagnosis, I have put great passion into the cause.

But sometimes I lose my balance, and the passion becomes obsession.

After speaking at Alnylam Pharmaceuticals in Cambridge, MA, on May 17 and holding a potential cure in my hands in the company’s lab, I couldn’t wait to share my excitement with others in the HD community. On the plane ride back from the East Coast on May 21, I worked on a blog article about the Alnylam trip non-stop for six hours.

My passion remained on full throttle when I arrived at home. I practically ignored my family and other activities for the next several days. Only after I posted the Alnylam article on May 25 could I start to come down from the trip.

A radio interview

In the midst of the Alnylam trip and its aftermath I needed to decide whether to take yet another huge step out of the "HD closet": going on the radio with two other advocates to talk about the disease and our personal situations.

I consulted with my wife and weighed the potential impact of the interview on my family and job. After giving up so many dreams because of Huntington’s disease, my wife doesn’t want our family, including our 10-year-old, HD-free daughter, to deal with the disease until it’s absolutely necessary.

My wife pointed out my obsession after the Alnylam trip. But she didn’t want the rest of the family to become obsessed.

That night I had a very long and intense dream about HD involving my relationship with my daughter. In the dream, as in life, I wanted her to know the truth about HD. But I also wanted to protect and guide her.

I ultimately decided that the opportunity to speak out on HD was too important to pass up. There was no time to think through the consequences. I would deal with them, whatever they might be, as they arose.

In short, I would improvise – just as Petit improvised during the planning and execution of his walk between the Twin Towers.

So, on May 26, just hours after posting the Alnylam article, I participated in a half-hour interview on the Clear Channel radio network. I explained the symptoms of HD and my family’s struggle with the disease, including my exit from the HD closet. (Click here for more on the program and to listen to the podcast.)

So far, I have received feedback on the interview only from people in the HD community. But I am preparing myself for eventual questions and comments by others, including people at work, where only one trusted friend knows about my situation.

‘HD doesn’t have me’

As another good friend observed as we discussed HD and professional commitments, a very fine line exists between passion and obsession. Indeed, because of that fine line, it’s very easy to fall off the tightrope.

This same friend pointed out that I must avoid letting my quest for the cure compromise my health. “You can’t let the ‘cure’ kill you,” he said.

I later remembered how, in a similar situation, some Huntington’s disease caregivers become burned out or even die before their loved ones because they fail to rest or seek enjoyment.

As I walk the Huntington’s high wire, I am reminded of the sage phrase repeated by a number of HD people I’ve had contact with in recent years: “I have HD – but HD doesn’t have me!”

HD indeed had me for a while following my Alnylam trip and the radio interview.

But I won back control over the Memorial Day weekend. As we shopped with our daughter for items for a barbecue we were hosting for friends, my wife smiled and put her arm around me lovingly.

HD no longer had me. I was back in the fold.

Holding the potential cure in my hand

After telling yet another audience of scientists about my family’s two-decade struggle against Huntington’s disease, I held a potential cure for HD in my hand during a visit to Alnylam Pharmaceuticals in Cambridge, MA, on May 17.

For me, it was like holding the most valuable substance in the world. I inherited the HD-causing gene from my mother, who died of the disease in 2006 at the age of 68. At 51, I have now reached the age when HD started destroying my mother’s brain, erasing her personality, and leaving her unable to walk, talk, eat, or care for herself in the most basic way.

HD is 100 percent genetic: unless drug hunters get a treatment on the market in the next few years, I will get symptoms.

As I held what seemed like a magic compound, held in a small, securely capped plastic container, I smiled. A treatment – and maybe even a cure – now seemed more possible than ever. And Alnylam – along with its partners Medtronic and the CHDI Foundation, Inc., the so-called “cure Huntington’s disease initiative – is indeed preparing intensively to start a clinical trial.

A shot of me holding the potential cure (photo by Dr. Mathias Kretschmer of Alnylam).

This was a historic moment. As I stood in the lab at the Alnylam (pronounced “al-NIGH-lam”) facility, I thought of all the years that our community of affected families and treatment-seeking researchers had waited for scientific breakthroughs.

I, the gene-positive HD person, caught a glimpse of a future filled with hope, even as I recognize that hope depends on further scientific breakthroughs and long odds. In the drug industry, 90 percent of clinical trials fail to produce a treatment.

ALN-HTT: white and flaky

“ALN-HTT” is the name Alnylam has given this candidate drug product, which is a solution containing the drug substance, the term scientists use for the active ingredient in drugs. It stands for “Alnylam” and “huntingtin,” the name of both the gene and protein that, when defective, cause HD.

The substance – an “siRNA,” or small interfering RNA molecule – is white and flaky.

ALN-HTT in the hands of Dr. Muru Murugaiah, an Alnylam principal scientist, in the company's lab (photo by Gene Veritas)

RNA interference (RNAi) was discovered in 1998 by Craig Mello and Andrew Fire in C. elegans, a species of worm. By interfering with the conversion of the genetic code into specific proteins, RNAi controls helps control the expression of genes and prevents problems from occurring in cells.

For their discovery, in 2006 Mello and Fire won the Nobel Prize in Physiology or Medicine.

At the outset, they and other scientists thought RNAi could not occur in mammals or humans.

Then, in the early 2000s, two teams of German scientists discovered that RNAi did indeed exist in cultured human cells (cells outside the body). In a presentation at the Dana Farber Cancer Institute this past January, Alnylam demonstrated that RNAi also exists in humans.

Gene silencing

This process is also known as “gene silencing.” RNAi can turn off practically any gene in the body. The discovery of RNAi virtually coincided with the completion of the Genome Project, which identified every gene in the human body.

Immediately, scientists embarked on making siRNAs to turn off harmful genes. Drug discovery companies in Europe and the United States sprung up to explore this breathtaking technology, seen by many as the genesis of a new, very large class of drugs for halting all kinds of disease.

Nobel laureate Phil Sharp started Alnylam in 2002. The company took its name from the middle star in the belt of the constellation Orion. “The star has a luminosity that is 250,000 greater than the sun, representative of the potential strength that RNAi therapeutics could bring to bear in human health,” the company states on its website.

No company has yet put an RNAi drug onto the market, but Alnylam is hoping to be the first. The company has a staff of about 175 and partners with large pharmaceuticals in the search for RNAi remedies. Last year Alnylam ended a five-year partnership with Swiss pharmaceutical giant Novartis, forcing Alnylam to lay off 25 employees, but Novartis continues to pursue drug possibilities using Alnylam experimental treatments. Alnylam has more than $300 million in cash to support its activities.

Alnylam research focuses on a range of diseases and conditions, including liver cancers, respiratory syncytial virus infection (affecting the lungs and breathing passages), ultra-high cholesterol, refractory anemia, and transthyretin-mediated amyloidosis. It also facilitates research on neglected tropical diseases. The company is working on five RNAi products for genetic diseases and aims to have them in advanced stages of clinical development by the end of 2015.

Aiming for a clinical trial

In 2005, Alnylam initiated a major Huntington’s disease research project, aiming not only to address HD but also to develop techniques that might prove useful against other neurological diseases. Because HD is 100 percent genetic, it provides an excellent test for the effectiveness of gene silencing.

Alnylam intends to use ALN-HTT to silence the huntingtin gene so that less huntingtin protein is produced to harm brain cells. If successful, the treatment would save brain cells from dying and slow down and possibly even reverse the course of Huntington’s disease.

Model of how siRNA drugs work: click to enlarge (Alnylam image)

A number of research labs have already demonstrated safety and effectiveness of this approach in transgenic mice that have HD-like symptoms. In preliminary studies, it’s also safe in monkeys.

The next step is a big one. Alnylam, Medtronic, and CHDI are preparing to apply in 2012 to the U.S. Food and Drug Administration (FDA) for permission to conduct a Phase I clinical trial of ALN-HTT in humans. Alnylam hopes to start the trial in a small number of HD patients once the application is accepted.

The goal of Phase I studies in general is to demonstrate safety and tolerability – that the drug does not cause adverse impacts. If successful, Alnylam would then proceed to Phases II and III, which would be designed to demonstrate the effectiveness of the drug.

Entering uncharted territory

This is all uncharted territory for the FDA, doctors, researchers, the biotech industry, and investors. Safety for the test subjects is of the utmost importance – but so is the need to find a treatment for those families facing the horrors of HD.

Getting ALN-HTT into the brain is a major scientific and medical challenge. Because of the blood-brain barrier, which protects the brain against foreign substances, many drugs cannot get into the brain. So a drug like ALN-HTT must be injected directly into the brain.

So, for the first time in history, doctors will attempt to treat a brain condition by implanting a device into the skull in order to inject a siRNA drug.

Doctors have already experimented with deep-brain stimulation by implanting electrodes into the brains of patients with Parkinson’s, epilepsy, dystonia, depression, and even HD, explained Dinah Sah, Ph.D., the head of the Alnylam HD team and Vice President of Research. The procedure has shown some benefit in Parkinson’s, but no known effect yet in HD.

Dr. Dinah Sah, Vice President of Research and the head of the Alnylam HD team (photo by Gene Veritas)

Recently a clinical trial demonstrated improvement in Parkinson’s patients who received gene therapy in which a virus was used to transport the genetic message into brain cells.

Physicians have also injected a cell growth stimulant (growth factor) into the brains of Parkinson’s patients. This last approach is still under study.

Alnylam has partnered with Medtronic, a leading maker of medicinal pumps, to devise a pump to be placed in the HD patients’ abdomens. Doctors will run thin tubing under the skin from the pumps to a nodule at the top of the patients’ heads, and from that point a very fine needle will run into the putamen, one of the regions of the brain most devastated by HD.

For all of this to happen, expert doctors in the procedure will conduct an operation on the clinical trial participants. Doctors will then administer ALN-HTT, which will be dissolved in a special solution, by filling the pump and allowing it to send the drug to the brain according to a schedule and in doses to be determined by the researchers.

Other possibilities

This is all just a very brief sketch of the Alnylam project. Soon I will be writing more detailed reports, which will examine how Alnylam and its partners developed ALN-HTT and hope to turn it into a successful drug to treat Huntington’s disease. These reports will also consider the many challenges involved in this quest for an siRNA treatment.

Remember, too, that Alnylam is not the only project seeking to control HD at its genetic roots. As I have noted in several articles since 2008, Isis Pharmaceuticals, Inc., of Carlsbad, CA, has devised a similar drug candidate to be applied directly in the brain (click here to read more). And Dr. Jan Nolta’s lab at the University of California, Davis, is experimenting with ways to use stem cells to introduce siRNA into the brain. For an overview of HD and gene silencing, see the excellent article by Dr. Jeff Carroll.

Isis and Alnylam operate a joint venture, Regulus Therapeutics, to research microRNAs, an even more recent discovery also involving RNA interference.

HD researchers aren’t banking on any one of these initiatives as the sole solution to HD. Although one of them could indeed turn out to be the “cure,” most researchers speak of the likely need for an HD “cocktail” of drugs that would stop or at least reduce the many harmful effects on the brain caused by HD.

Seeking patient input

To assist with the HD project, last November Alnylam signed an agreement with CHDI, a multi-million-dollar effort backed by an anonymous donor. CHDI is pumping money into the project and lending its expertise in Huntington’s disease.

The crucial CHDI collaboration will reinforce Alnylam’s efforts to design a safe Phase I trial.

To that end, Alnylam is also seeking to learn more about the patients and gene-positive people whom it hopes to benefit.

After watching my keynote speech at CHDI’s Sixth Annual HD Therapeutics Conference in Palm Springs, CA, on February 7, Dr. Sah invited me to give a similar presentation at the company. My May 17 visit inaugurated a new Alnylam initiative to involve patient advocates in order to put a human face on the conditions they seek to alleviate.

During the Q & A after the speech, attended by about 50 people, Alnylam executives and scientists were anxious to hear my opinion about several aspects of clinical trials.

The desire to function normally

One scientist wanted to know what people affected by HD community would consider to be a successful treatment. Obviously we all want a “cure” that completely eliminates the disease, I responded. But short of that, we need something that would at least allow us to continue to function normally. If someone suffered from chorea (the shaking and trembling caused by HD), a good drug would at least prevent that person from also losing the ability to think and speak.

We also need a drug that would prevent HD from erasing an individual’s personality by preventing the behavioral, emotional, and cognitive problems. HD, I said, had stolen my mother’s personhood.

One doctor asked: what if we fail and no treatment results from this experiment?

I responded that I recognized that failure is a part of science. You don’t know if something will work unless you try it, and if it fails, then you know it’s time to proceed to other alternatives.

However, I told the audience that I personally do not think about failure. The project must succeed! At that, many people nodded enthusiastically, and one of the executives said: “We agree with you!”

At that moment, I felt a special bond with everybody in the room. We were all rededicating ourselves to the quest for the cure – although everybody also recognized that failure remained a distinct possibility.

Avoiding hurdles, gaining speed

Afterwards I met with CEO John Maraganore, Ph.D., President and COO Barry Greene, Dr. Sah, Doug Macdonald, Ph.D., of CHDI, and Jules Greenwald, the development director for the Huntington’s Disease Society of America (HDSA). I took the opportunity to interview Maraganore and Greene.

Both stressed the need to prepare an effective Phase I application to the FDA and to convince the agency of the urgency of getting an siRNA treatment to HD patients.

“It’s important for us to have a dialogue, which includes patient advocates, with the FDA and other regulatory agencies, so that they appreciate the significant burden that the disease has on patients and their families,” Greene said.

“I think they know the disease, but they don’t really know the face of the disease,” Dr. Maraganore said.

Barry Greene (left), Gene Veritas, John Maraganore, and Dinah Sah

Much of the upcoming discussion with the FDA will revolve around the question of how fast Phase II and Phase III of the trial can go. If the FDA requires an extremely long efficacy study – from seven to ten years – the costs could become prohibitive and scare off funding sources, like investors, Greene explained. For patients and success, “speed really matters,” he said.

Another crucial question involves determining “endpoints.” In this case, an endpoint would be an observable change in a specific symptom and/or a change in the level of defective protein in the brain cells or some other marker of the drug’s effects (biomarkers).

Measuring huntingtin protein levels would likely prove the quickest endpoint, although it’s not clear if a lower level of huntingtin in humans will diminish symptoms the way it has in mice.

“We … want to have a testing approach that doesn’t create undue hurdles to the point where you actually make it so difficult to prove that something is maximally safe and maximally effective,” said Dr. Maraganore in summarizing the challenges. “So you want to have the right balance.

“The urgency? The need? I think you said it: You have more to lose now than ever,” he continued, referring to my race against time as I await a treatment. “That’s the level of urgency that needs to be put into this equation in terms of how these medicines are developed. That can only be said by a patient."

Hanging out with the scientists

My day at Alnylam was one of the most intense of my entire life. This article doesn’t even scratch the surface of what I experienced.

But Alnylam also planned some relaxation.

I enjoyed hanging out with the scientists at lunch and dinner, and I was impressed by their humanity and openness to new and different perspectives.

I had contemplated removing from my speech a mini-meditation exercise involving a demonstration of deep breathing, and also my discussion of the question of God, HD, and the Jesuit priest-scientist Teilhard de Chardin. But I was glad I didn’t. To my great surprise and joy, Sara Nochur, Ph.D., the Vice President for Regulatory Affairs, had read Teilhard’s works, and her husband had just completed a book on the topic of the link between science and the transcendental and also knew Teilhard’s writings. As we walked back in the rain to the office, Dr. Nochur and I compared notes on meditation and breathing as coping mechanisms.

At dinner Martin Goulet, Ph.D., who handles non-clinical experiments in the Alnylam lab, and I talked about our families. He has a girl about the same age as my HD-free ten-year-old daughter.

Dr. Martin Goulet (right) at work on the Alnylam HD project (photo by Gene Veritas)

Getting out the word on trials and the cause

Over the next few days, I excitedly told other people in the movement that I had held ALN-HTT in my hand. I felt like an apostle spreading news of a religious revelation.

My journey did not end at Alnylam. On May 18 I flew to New York City for meetings with other leaders of the HD movement. That day I visited CHDI headquarters in Manhattan, where communications director Simon Noble, Ph.D., and I discussed at length ways of getting out the word about the need for involvement in upcoming clinical trials.

On May 19, I spent most of the day at HDSA. I gave an informal talk to the staff about my situation and advocacy. I also interviewed CEO Louise Vetter, now in her third year at HDSA. In line with the theme of clinical trials, we discussed the HDSA Clinical Trial Ambassador program, which will utilize experienced members of the HD community to promote awareness about the trials and answer potential participants’ concerns.

On May 20, I traveled to Princeton, NJ, to interview scientists from CHDI’s clinical trials division.

The visit began with an informal brainstorming session at the home of Maria Beconi, Ph.D., the director for drug metabolism and pharmacokinetics (how drugs are absorbed, distributed, and excreted from the body).

After we consumed pizza, soft drinks, brownies, and cupcakes, Maria introduced me. I thanked the team for its commitment to HD research and explained that I was tracking the social history of the HD movement and the work of the scientists towards treatments and a cure.

I’ll be writing more about this issue and the CHDI unit in a future article.

In New York I met up twice with my friend and “HD alter ego,” Norman Oder, who edits this blog. We caught up on each other’s lives, and we discussed strategies for broadening the message of the HD cause.

Alnylam: passionate about HD

In 2008, when I first studied the Isis HD project, I fantasized about wearing a drug-injecting pump on my head. That was a somewhat inaccurate fantasy, because the pump would not be located on the head itself, but in the abdomen. Isis plans to use this kind of system. But even if it were located on the head, I would gladly use it – or any other device in any other location, for that matter.

Likewise, I would happily accept the implantation of an ALN-HTT pump in my abdomen. My need to avoid HD far outweighs any potential inconvenience caused by such devices.

I came away from Alnylam energized by its scientists’ seriousness, intelligence, practicality, and commitment to stopping HD. “We are very passionate about this disease and finding a cure for it,” Dr. Maraganore told me at the end of our interview.Dr. John Maraganore (Alnylam photo)

Dr. Maraganore told me that Alnylam will likely call on me again, as well as other patient advocates, to offer advice on the design of the clinical trial and to put a human face on the disease for the FDA.

Holding the cure is not enough

During the Q &A after my speech and the interview with Maraganore and Greene, I had an uneasy sensation in my gut. Alnylam’s scientists wanted not only to learn about my personal struggle against HD: they also wanted me to become involved in the strategizing for a clinical trial. I suddenly felt myself taking on a new, challenging, and immense responsibility in my HD advocacy. Though I have no training in science, I need to increase my knowledge of HD, the research for treatments, and the clinical trial process.

Dr. Maraganore observed that, as a result of Alnylam's new collaboration with CHDI, the company was "smarter about what we need to do" to get ALN-HTT into trials. "By being smarter, we're going to be faster," he added.

I, too, felt a bit smarter after meeting the Alnylam team. And I need to get even smarter as we all move together towards this potentially historic treatment.

Holding the potential cure in my hands is just the beginning. I must do my part to help get that cure into our patients and ultimately into me.

(Note: because Alnylam invited me to speak and visit its facility, the company paid for my round-trip airfare to the East Coast, my hotel in Cambridge, and meals related to the visit. I maintained the right to express my opinion in this and other articles on the HD project. )