Wednesday, May 20, 2015

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!)

Sunday, May 10, 2015

Deciphering signals from Huntington’s disease brains in the search for treatments

From coast to coast and around the world, scientists like Andrew F. Leuchter, M.D., and Michael Levine, Ph.D., are engaged in the quest for Huntington’s disease treatments.

During May, Huntington’s Disease Awareness Month, I want to call attention to the critical work of Drs. Leuchter and Levine on the West Coast. They exemplify the partnership of scientists and physicians with the HD community, aiming to advance potential remedies into crucial clinical trials.

Drs. Leuchter and Levine, faculty researchers at the renowned Semel Institute for Neuroscience and Behavior at the University of California, Los Angeles (UCLA), are collaborating on a project that could ultimately lead to new drugs. In the near term, they aim to understand more fully the electrical signals that naturally but abnormally emanate from the brains of HD patients and presymptomatic carriers of the HD gene mutation like me.

“Most of the brain’s energy goes to creating electrical gradients – electrical impulses – but we haven’t been very good at using that for diagnosis and treatment,” Dr. Leuchter said during a March 20 interview in his office at the Semel Institute. He and Dr. Levine aim to “decipher the signals that are coming out of the brain.”



The Semel Institute for Neuroscience and Behavior (photo by Gene Veritas)

Measuring brain energy

A psychiatrist specializing in depression and Alzheimer’s disease, Dr. Leuchter (pronounced LUKE-ter) frequently employs quantitative electroencephalography (quantitative EEG) to measure the energy emitting from people’s brains. One example: a group of 27 HD subjects he and others observed for a study published in 2010 and funded by CHDI Foundation, Inc., the nonprofit virtual biotech dedicated exclusively to the discovery of HD treatments.

Allan Tobin, Ph.D., at the time the head of UCLA’s Brain Research Institute and a senior scientific advisor at CHDI, had asked colleague Leuchter for assistance in finding HD biomarkers, signals that reveal the progression of the disease and/or the effectiveness of a medication.

As the number of HD clinical trials expands exponentially, the search for useful biomarkers has become one of the hottest areas in Huntington's disease research. (Click here to read about one new potential biomarker.)

As Dr. Leuchter pointed out, neurological and psychiatric disorders are “much more limited in diagnostic tests for the organ that we are studying than any other branch of medicine.” Cardiologists insert catheters into the heart, and gastroenterologists use scopes to view the stomach and intestines.

“If you’re a psychiatrist, we talk to people, which is great, but we don’t have physiologic tests that guide decision-making,” he added.

Scientists and doctors rarely put electrodes in living human brains or take biopsies of brain tissue. However, they have been measuring brain energy with EEGs for more than a century, Dr. Leuchter explained.

As he demonstrated in his lab (see photo below), today patients undergoing testing wear a cap with 35 separate EEG electrodes, or contacts, that touch the head. The attending researcher stretches the cap over the patient’s head. In contrast with the traditional EEG, which involves one-by-one placement of the electrodes on the head, this method is quick, efficient, and less burdensome to patients, he noted.


Above, Dr. Andrew Leuchter points out the electrodes on the EEG cap worn by research subjects. Below, he explains digitized EEG readings displayed on a computer monitor. (photos by Gene Veritas) 


“We find that this helps to standardize our measurements of brain activity, and that we can place the electrodes in about 15 minutes,” Dr. Leuchter said.

EEG is inexpensive, convenient, and easy to administer. Additionally, it does not expose patients to radiation or require them to lie inside a machine such as an MRI scanner, he noted.

“You can tote it wherever you like,” he said of the EEG device.

The brain’s pacemaker

As they had hoped, Dr. Leuchter and three other UCLA researchers discovered abnormal EEG readings in HD patients with just mild symptoms.

“But the really intriguing thing there was that, even in people who were gene-positive but premanifest, we could see differences in brain function estimated 15, 20 years out from diagnosis,” Dr. Leuchter said, referring to signals of future decline. “So we thought this could be something that could be useful for treatment development.”

As Dr. Leuchter explained, “the brain like the heart has pacemakers.” Healthy brains produce lots of high-frequency waves. Brain illnesses commonly result from changes in the firing of the pacemaker, resulting in a greater quantity of low-frequency waves.

“What we found is that years before people start to show symptoms with Huntington’s, they’re producing more low-wave energy,” Dr. Leuchter said. So it’s a very subtle indicator that the pacemaker of the brain is starting to slow down.”

Scientists cannot predict the actual onset and progression of symptoms from EEG signals. However, as noted below, they did discover a correlation between the severity of genetic mutation and EEG readings.

Clear genetic impact on the brain

Furthermore, the team observed that, in contrast with healthy brains, the distribution of different types of waves across the different regions of the HD brains became more uniform. “The regions of the brain start to look more similar than different,” he explained.

Researchers have not yet discovered what this phenomenon means.

“We know that the brain has enormous functional reserve and that people call on every cognitive and emotional resource they’ve got to try to keep everything functioning at optimal efficiency,” Dr. Leuchter continued. I don’t think we know what’s compensatory and what’s an early sign of illness.”

Reflecting on another facet of the research, Dr. Leuchter explained that, in general, brain function tests do not correlate with genetic factors.

However, he and his team did find a correlation between the degree of HD genetic mutation and the severity of the changes in the EEG readings.

“Nobody had seen that,” he recalled. “We got excited about that, and that’s what we’ve been trying to follow up on.” These findings will contribute to the search for biomarkers and treatments, as explained below.

Examining brain tissue

A neurophysiologist and veteran basal ganglia researcher, since the late 1960s Dr. Levine has studied these deep, inner parts of the brain that control such actions as voluntary movements. He began to study HD in the 1990s as genetic mouse models with HD-like symptoms became available. His lab has published more than two dozen papers about these mice.

The nuclei of the basal ganglia are significantly compromised in HD, especially in the striatumSpecifically, Dr. Levine has examined how neurons communicate with each other in the cortex and striatum at cellular and molecular levels using tissue from the HD mouse models.

One of the latest techniques for studying the cells in the HD mouse models is optogenetics, in which specific types of brain cells are stimulated with light.

“I can look very closely at mechanisms,” Dr. Levine explained. “I know which types of neurons I am looking at and how they change at a very mechanistic level.”


Michael Levine, Ph.D., veteran HD researcher (photo by Gene Veritas)

Two key goals

Melding approaches, and with the expectation of CHDI support, Drs. Leuchter and Levine now seek to answer two important questions.

The first involves comparing EEG data from both mice and humans to refine the search for biomarkers. Researchers have already made the key discovery of EEG signals common to mice and humans.

“It’s actually pretty uncommon in science that you can see a very similar signal across species, that you can see something very similar in the brains of humans and the brains of animals,” Dr. Leuchter said.

If the Leuchter-Levine project confirms the degree of that similarity, that could mean  potential drugs tested in mice could ultimately be used for human clinical trials, Dr. Leuchter observed.

The second question focuses on the testing in HD mice of a CHDI-developed compound aimed at lowering the amount of mutant huntingtin protein, the major culprit in the disease.

“If we do see a link between lowering of mutant huntingtin and change in the EEG biomarker, this could be used to develop a number of therapeutic agents,” Dr. Leuchter said. “A whole line of research could develop out of this.”

From molecule to the whole brain

Drs. Leuchter and Levine estimated the project will take two years to complete.

As Dr. Levine put it, researchers hope the CHDI-developed compound will restore the EEG signals in HD patients to normal.

Dr. Leuchter reflected on the significance of the project and his collaboration with Dr. Levine: “The fact that in something like Huntington’s disease you’ve got a protein that is affecting how the nerve cells are functioning and altering the way they produce and utilize energy – it’s really a gateway to understanding the connection between what is going on at the deepest molecular level of the cell and what we’re able to see with the brain waves the individual is putting out. We can actually potentially link everything going from the level of the gene all the way to whole-brain function.”

In another potential future project, Dr. Leuchter would like to obtain EEG readings from asymptomatic gene carriers over two to three years to better measure the changes in signals over time.


Drs. Leuchter and Levine (photo by Gene Veritas)

Participation and a positive attitude

Both researchers expressed gratitude to the HD community and fellow HD researchers for their dedication to the cause.

“There are not that many people with this illness, so people get asked a lot to participate in different studies where they’re poked or prodded or scanned,” Dr. Leuchter said. “We are very grateful to those who are so generous with their time, because without their help we could not conduct these research studies.”

Dr. Levine added that he is impressed with the “very positive and sharing attitude of the investigators who do research in HD and who are looking to help the patients.”

While interviewing these two researchers, as an individual racing against the genetic clock of HD, I was once again moved to witness the creativity and enthusiasm of scientists engaged in the quest to save affected families from the devastation of Huntington’s.

(Later this month: from the East Coast a report on Yale School of Medicine researcher Doug Rothman, Ph.D., and the mystery of the mitochondria in Huntington’s disease. Please remember during HD Awareness Month to donate generously to the Huntington’s Disease Society of America or the HD cause of your choice!)

Monday, April 20, 2015

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

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

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

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

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

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

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

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


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

A historic attack on the genetic roots

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

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

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

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

Being realistic

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

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

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

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

You can watch my speech in the video below.

Returning to Yale

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

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

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

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


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

A science tour and lunch with old friends

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

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

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

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

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


Paul and Carole Bass (photo by Gene Veritas)

Supporters of the HD cause

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

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

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

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

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

Quiet resolve

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

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

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

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

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


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

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

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

Tuesday, April 07, 2015

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

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

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

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

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

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

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

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

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

People deciding at their own pace

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

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

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

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

What a journey!

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

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

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

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

Activists’ self-respect

I have received enormous respect from my fellow HD advocates.

We activists must always remember to respect our own journeys.

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

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

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

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

Enjoying the present, planning the future

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

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

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

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

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

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

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

Affirming the good in our lives

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

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

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

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

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

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

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