A new, more holistic view of Huntington’s disease: the systems/P4 approach

When I learned in late 1995 that my mother suffered from Huntington’s disease, a disorder unknown to my family, my reaction went from perplexity to utter shock as I listened to the details: HD caused shaking and severe dementia, was fatal, and had no treatment or cure.

Over the next decade, as my mother lost the ability to walk, talk, eat, and care for herself, her doctors could do little to help.

With a 50-50 chance of inheriting HD, I felt desperate as I waited in limbo. In 1999, my positive test for HD multiplied my fears.

When my mother died in 2006, a treatment didn’t even appear remote.

Even today, the medicines prescribed for HD patients treat only symptoms, sometimes with serious side effects. They do not arrest the disease in any way.

The lack of therapies (a medically more appropriate word than “treatments”) devastates affected families, perhaps more than any other of the cruel realities of HD.

However, as I described in my previous two articles, leading HD researchers are planning for eight new clinical trials in just the next two years (click here and here to read more).

The vastly increased knowledge of HD’s causes and the very real possibility of effective therapies behoove us to think about HD in a radically new way. Instead of reacting with the traditional (and quite understandable) fear and pessimism, I believe we must now embrace hope and optimism.

Rather than anticipating the worst, we must expect the best, even if we cannot predict the timetable.

Shifting from ‘incurable’ to ‘treatable’

To turn the emotional tide and spur greater patient and family involvement in crucial research and clinical trials, the HD community must replace the phrase “HD is incurable” with “HD is treatable” or, perhaps more precisely, “HD will be effectively treatable.”

“For so long we’ve talked about HD as an incurable disease,” I told an audience of some 100 people at the southern California Huntington’s Disease Regional Education Day at the University of California, Irvine, on March 10, sponsored by the Huntington's Disease Society of America (HDSA), Lundbeck, and Remind. “That keeps people behind the mask, keeps them in the closet, keeps them in denial. But the fact that you have the trials coming on line means that this statement is no longer accurate. It’s no longer an incurable disease. I believe it’s a disease that’s going to be treated, and going to be treated successfully sometime in the next five to ten years.

“So going back to the old HDSA phrase of some years ago: let’s make this the last generation with HD. I believe it’s going to be the last generation with HD, or that has HD in the way we’ve known HD, because I think we’re going to be controlling and managing HD.”

You can see the entirety of my speech in the video below.



Solid reasons for hope

People have occasionally cautioned me against raising false hopes, warning that if a potential drug fails, some in the HD community might withdraw from involvement in research and clinical trials. Many remember how in the early 2000s some people placed great hope in LAX-101 (also known as Miraxion or ethyl-EPA), a fish-oil extract, only to experience a letdown after mainly ineffective clinical trial results.

The cold, hard fact is that 90 percent of all clinical trials do not produce an actual drug. It takes time for scientists and drug companies to develop, test, and fine-tune drugs.

Furthermore, scientists do not view those 90 percent as unsuccessful or “failures.” Rather, a trial that ends without a successful therapy simply indicates that researchers should make a correction in the path or choose a different one.

Therefore, we must not give up if a trial or therapy does not fulfill our personal expectations. Drug discovery requires the participation of the entire HD community. Only by working together can we assemble all of the pieces of the therapy puzzle.

I also think that we have solid reasons for hope.

Having followed HD research the past 15 years, I believe the current lineup of planned trials stands out as qualitatively far different from LAX-101 and other supplement-like substances in other trials or drugs originally designed for other conditions that didn’t prove effective in HD.

The new generation of potential drugs benefits from new biological discoveries (such as RNA interference), new drug-discovery technologies (such as high-throughput screening), and a much greater (though still far from complete) understanding of how HD damages the brain.

In addition, in the words of Dr. Robert Pacifici, the chief scientific officer of CHDI Management, Inc., the multi-million-dollar HD therapy initiative, the new HD drug candidates are “custom-crafted” for HD.

A visionary turns to HD research

The annual CHDI HD Therapeutics Conferences provide a panorama of the progress in HD research. I am preparing a report on the scientific findings of the seventh conference, held February 27-March 1 in Palm Springs, CA.

Here I want to reflect on one speaker, Dr. Lee Hood, whose scientific vision is beginning to influence the search for HD therapies.

An M.D., Ph.D., Dr. Hood worked with colleagues to invent four instruments important for the success of the Genome Project (as well as other research): the DNA sequencer and synthesizer and the protein sequencer and synthesizer. Dr. Hood helped to found 14 biotech companies, holds 30 patents, and stands among only ten people in the world to belong to all of three major American scientific organizations, the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. In 1987 he won the Lasker Basic Medical Research Award (the American equivalent of the Nobel Prize).

In 2000, Dr. Hood founded the Institute for Systems Biology (ISB). Located in Seattle, the non-profit ISB teams scientists and technologists from many disciplines to pioneer the future of research in biology, biotechnology, medicine, environmental science, and science education. Dr. Hood is the ISB president.

Dr. Lee Hood at the 7th Annual CHDI HD Therapeutics Conference (photo by Gene Veritas)

When he turned 70 in 2008, Dr. Hood stated that he aimed to achieve the “most ambitious things … in my career,” including the advancement of systems biology and advocating for the widespread adoption of “proactive P4 medicine” (predictive, preventive, personalized, and participatory).

Among other cutting-edge collaborative projects, ISB has pioneered proteomics, the study of the more than 23,000 proteins in the human body.

“What we’ve done is to democratize proteins – that is, make them accessible to all biologists – just as the Human Genome Project democratized genes and made them available to all biologists,” Dr. Hood told the audience at the HD Therapeutics Conference.

A new, even more exciting project aims to develop “global proteomic analysis” by digitizing all of the human peptides (the chemical building blocks of proteins), Dr. Hood added. Just as people can hone in on a geographic location using Google Earth, scientists will soon compare peptides in a digital catalogue, he said.

The next stage will involve studying proteomics and genomics together, he said.

The importance of systems biology

In his HD Therapeutics Conference presentation, “Systems Approaches to Neurodegenerative Diseases and the Emergence of Transforming Technologies,” Dr. Hood explained systems biology (SB) and how it can impact the search for HD therapies.

SB emerged because of two revolutions: Darwin’s work on evolution, which revealed the enormous complexity of biology and disease, and the late-20th-century explosion in digitized biological information.

“We need this thing called systems biology to de-convolute that complexity,” Dr. Hood stated.

In a nutshell, SB offers a holistic view of disease. In Dr. Hood’s words, the body is a hierarchical “network of networks” that interact – beginning with genes, extending to molecules, reaching the organs, rising up to the individual human, and ultimately including society and the physical environment.

In my own shorthand, I think of SB as the “big picture of disease.”

SB uses the power of computing to mine, integrate, and visualize very large and complex sets of biological information, Dr. Hood added.

He described the SB approach to disease as providing an “informational view of science” that seeks to “capture the dynamics of disease.”

In this approach, biology drives technology, which in turn drives analytical tools (computation).

“It’s this holy trinity of biology driving technology driving computation that’s really at the heart of systems biology,” Dr. Hood explained. “I realized this first in the context of developing the automated DNA sequencer.”

SB scientists seek to tackle a complex system like HD, build a model of the disease, test that model, and then “perturb” its system repeatedly to see the disease mechanism at work. From this experimentation, they draw conclusions about the disease and how to treat it.

Hunting for HD modifier genes

In collaboration with leading HD specialists, ISB has set out to identify modifier genes for HD. HD results from a mutated form of the huntingtin gene, but one or more modifier genes may affect the onset of the disease. This would help explain why onset occurs at different times in people with the exact same degree of mutation.

To conduct this research, ISB has resorted to the SB approach of gathering large amounts of genetic information.

“We’ve now analyzed more than 60 human genomes from families that have Huntington’s disease,” Dr. Hood told the HD Therapeutics Conference audience. “What we’ve found is these families place enormously interesting constraints on areas where you may find modifiers, but we don’t have sufficient data at this point to really identify candidates. What we’re excited about is integrating these data together with the GWAS (genome-wide association study) data that will be coming later in the year.”

SB and a better understanding of HD

Dr. Hood concluded that SB can assist a search for HD therapies in four other ways. First, it can bring “new insights” into how HD works.

Secondly, “we can make blood into a window for health and disease” by discovering and measuring markers of “drug toxicity as well as disease diagnostics.”

Third, in line with its holistic outlook, SB provides “new approaches to analyzing multi-organ responses.” So far, most HD research has focused on the brain. However, scientists know that the huntingtin gene is expressed in every cell in the body and affects muscle and fat.

Fourth, SB presents “new approaches to drug target discovery” that could speed the arrival of therapies.

Finally, Dr. Hood added, “the digitization of information is going to be absolutely fascinating,” allowing scientists ever greater access to what happens in HD patients and helping them to plan treatments.

You can watch the entirety of Dr. Hood’s presentation in the video below.



P4: predictive, preventive, personalized, participatory

SB is laying the basis for P4 medicine, which holds great relevance not just for HD, but all diseases and the promotion of wellness in a future global system of health.

“P4 medicine, the clinical face of systems medicine, has two major objectives: to quantize wellness and to demystify disease,” Dr. Hood and a co-author write in an article in the March 2012 issue of the journal New Biotechnology that he sent me shortly after the HD Therapeutics Conference. “Patients and consumers will be a major driver in the realization of P4 medicine through their participation in medically oriented social networks directed at improving their own healthcare.”

Several organizations have partnered with ISB to pioneer programs in P4. If it is implemented on a wide scale, Dr. Hood predicts that it will revolutionize our healthcare system. Costs will plummet, everybody will carry a health monitoring device, and diseases will be predicted and prevented long before onset as the result of tiny blood samples taken from a pin prick, the article states.

“P4 medicine will not be confined to clinics and hospitals,” the article continues. “It will be practiced in the home, as activated and networked consumers use new information, tools and resources such as wellness and navigation coaches and digital health information devices and systems to better manage their health.”

Care will be “tailored to the circumstances of each individual.”

An amazing transition

Systems biology and P4 medicine provide a vastly different picture of Huntington’s disease from the largely hopeless one painted for me and my family after my mother’s diagnosis in 1995.

And we felt so alone in the impersonal world of traditional medicine.

The fresh, fundamental SB/P4 approach has led to a deeper understanding of the work that lies ahead in the search for HD therapies.

CHDI has adopted the SB approach by hiring one of its key practitioners, Dr. Keith Elliston, to serve as its vice president of systems biology. Dr. Elliston also spoke at the HD Therapeutics Conference.

Dr. Keith Elliston (in cap) confers with scientists at the HD Therapeutics Conference (photo by Gene Veritas).

“I’m also very excited that CHDI has chosen to embrace systems biology and to make that a key tenet of its drug-discovery process,” Dr. Nathan Goodman, an ISB researcher and member of an HD-affected family, told the audience. “In essence, this makes CHDI the first systems-biology-driven therapeutics company, yet another in the long line of firsts that CHDI has accomplished. This is a very big step not just for the Huntington’s disease field, but for all of biology, all of life sciences, the entire industry of therapeutics. This is an amazing transition by CHDI.”

As SB and P4 could very likely represent the future of medicine, I’m betting they will also play a major role in removing HD as a threat to me, my family, and the tens of thousands of families around the world impacted by HD.

We in the HD community have fulfilled the first P: genetic testing allows us to predict our future.

We now must focus on the other Ps: preventing HD; receiving personalized diagnosis and treatment that will optimize our health; and attaining wellness and a long life as a result of having helped find effective treatments through proactive participation in HD research and clinical trials and the contribution of our biological information to a global data bank.

The first dose is hope: moving towards treatments for Huntington’s disease

With its incurable genetic attack on the brain, Huntington’s disease wreaks havoc on its victims and their families, leaving them helpless, bereft of hope. I felt powerless as I watched my own HD-stricken mother become a mere shadow of herself and then worried about my own onset after testing positive for HD in 1999.

However, we have reason for hope. After many years of quiet but steady progress, drug makers are beginning to harvest significant results in the quest for treatments.

Since my mother’s death in 2006, I have seen scientists move from cautious optimism to optimism and now to genuine optimism.

At the 7th Annual HD Therapeutics Conference last week in Palm Springs, CA, I observed how many of the world’s leading HD researchers are preparing for clinical trials of remedies that could prolong and improve the lives of patients – and prevent me from becoming symptomatic. Notably, this year’s conference included many pharmaceutical companies: Alnylam, Isis, Medtronic, Novartis, Pfizer, Sangamo BioSciences, and Vertex.

As I participated in the conference, I felt hope come alive for the HD community.

Scientists pushing forward

I witnessed hope in the scientists’ confident smiles, animated conversations, and enthusiastic handshakes – including that of Dr. Robert Pacifici, the chief scientific officer of CHDI Management, Inc., the multi-million-dollar HD treatment initiative and the organizer of the conference.

Dr. Robert Pacifici (left) and Gene Veritas

“There are now eight things with the potential to reach the clinic in a two-year time horizon and a bunch more behind that,” Dr. Pacifici told me in an interview.

I also encountered optimism in Dr. Jim Gusella, whose research team found the general location of the HD gene (the marker) in 1983 and, in 1993, cloned it, making possible a simple, 100-percent accurate genetic test for the disease.

In many ways, his historic work laid the foundation for today’s advances. His current work includes the search for modifier genes – genes that, in addition to the HD gene, might affect the onset of the disease.

But scientists require an engaged HD community. In an interview, Dr. Gusella told me that patient participation is “incredibly important” in the drive for treatments.

“You cannot study a human disease without studying the people who have the human disease,” he explained. “You can’t test a drug unless you have people to test it on to see whether it does anything. The more they can participate, the better, whether it’s just giving a blood sample or going in and having neurologic exams to look at progression of disease or participating in a clinical trial.”

And, Dr. Gusella added, the community must maintain hope.

Dr. Jim Gusella (left) and Gene Veritas

Lowering huntingtin

Above all, I saw hope personified in the conference’s two dozen presentations and nearly 100 posters – all of them focused on the goal of understanding HD more deeply and/or developing treatments.

As I strived to process the vast information of this highly compressed 72-hour event, I felt exhilarated at the prospects of being freed from the threat of HD.

I paid special attention to the sessions on “lowering huntingtin,” a variety of strategies for reducing the amount of defective protein in brain cells. These strategies seek to block HD at its genetic roots, thus ameliorating or preventing symptoms.

I’ve followed one of these initiatives, a collaboration between CHDI and Isis Pharmaceuticals, Inc., since early 2008 (click here to read more).

I was thrilled to watch Dr. Frank Bennett, the Isis senior vice president of research, present an update . This year or next, Isis likely will apply to the federal Food and Drug Administration for a Phase I clinical trial to test the safety of its “antisense” technology, a class of substances known as “oligonucleotides,” or “oligos,” which would interrupt the production of defective proteins.

Isis, CHDI, and academic collaborators such as the HD lab of Dr. Michael Hayden at the University of British Columbia achieved an important breakthrough by discovering a way to lower defective huntingtin proteins while allowing normal huntingtin to carry on its vital tasks in the brain cells.

Isis has demonstrated the feasibility and safety of lowering huntingtin in mice, rats, and non-human primates.

Significantly, the Isis oligos have helped alleviate symptoms in HD mice.

An excellent scenario

Sitting cross-legged on the floor in front of the podium, I snapped photos of Dr. Bennett’s slides and listened intently to each word.

It was like having a front-row seat at a grand theatrical production – but one that was about me and the hundreds of thousands of people around the world affected by HD as patients or gene-positive people awaiting onset.

Dr. Frank Bennett (right) and Gene Veritas (photo by Dr. Ed Wild)

We wait as the actors, these scientific heroes, unravel the plot towards effective treatments.

“CHDI like a dream – couldn’t have imagined a better scenario,” I wrote in my notes. “Incredible vision with gene silencing.”

(Later this year I plan to pay my fourth visit to the Isis labs in Carlsbad, CA, to prepare a detailed update on the project.)

Inspiring connections

As we depend on the scientists literally to save us from HD, they also depend on the HD community for inspiration.

In remarks to the audience, Dr. Ladislav Mrzljak, CHDI’s director of neuropharmacology, recalled my 2011 CHDI keynote speech. Dr. Mrzljak told me personally that my speech had inspired him as he assumed his new role at CHDI after eleven years at the pharmaceutical giant AstraZeneca.

After one speaker noted that a researcher at my alma mater, Yale, had received a CHDI grant, I asked Dr. Mrzljak for details. Not only did Dr. Mrzljak personally know the researcher; he himself had spent the 1990s at Yale studying with world-famous cognitive neuroscientist Patricia Goldman-Rakic.

Dr. Mrzljak presented evidence that a CHDI-designed compound (CHDI-246) produced positive effects as measured in brain samples taken from HD mice. Research on CHDI-246 continues.

Dr. Ladislav Mrzljak (photo by Gene Veritas)

In addition to scientific veterans, this year’s conference included many young poster presenters. I met Julie Harness, a Ph.D. student specializing in HD stem-cell research at the University of California, Irvine (UCI).

Using both normal and HD-affected embryonic stem cells derived from discarded blastocysts from couples who opted for pre-implantation genetic diagnosis, Harness seeks to understand the causes of HD and perhaps develop an approach to treatment, including drug discovery. (Click here for more on California’s HD stem-cell-research. In a future article I will explore UCI’s HD research in depth.)

Harness told me that she felt inspired to present a poster this year after seeing photos of posters from last year sent by another UCI graduate student who had attended the 2011 meeting. Perhaps I took those photos – because I have included poster photos in this blog and since 2010 have supplied CHDI with a CD containing photos of all posters.

Julie is also a reader of this blog.

Julie Harness and her poster on a stem-cell drug-discovery platform for HD (photo by Gene Veritas)

Coming down to the wire

Despite the positive outlook, participating in the conference also magnified my fears of onset. My mother’s symptoms apparently began in her late 40s. At 52, I count each day without the classic symptoms – chorea (shaking), cognitive loss, and mood disorders – as a bonus.

I wondered: will the clinical trials prove successful, and will the medicines come in time to save me? If I become ill, will they help me recover?

As I watched Dr. Sarah Tabrizi’s slides demonstrating significant changes in the brain before classic onset, my heart sank. She stated that these changes begin as early as 20 years before predicted onset.

I glanced over at Jeff Carroll, a recently minted Ph.D. who is emerging as a leader in HD research. His poster – a study of HD mice and cell metabolism that suggests another potential approach to treatment – won first prize. Dr. Carroll, 34, is also gene-positive for HD and, like me, places great hope in the Isis project. His research has contributed to that project.

Dr. Jeff Carroll ponders Dr. Bennett's Isis update (photo by Gene Veritas).

“We’re fried!” I thought to myself as I viewed images of the brain shrinking.

To my relief, Dr. Tabrizi pointed out that, despite significant changes in the brain, “premanifest” individuals maintain an almost normal level of cognitive abilities.

“Despite striking brain changes, premanifest HD gene carriers did not deteriorate significantly over 24 months in cognition or motor function tasks,” she said in reference to the TRACK-HD study that she headed. “I think that tells us that the brain is functionally plastic and is compensating. And the good news is that there may be a lot to rescue.”

“We gene positive are really coming down to the wire!” I wrote in my notes. “Can we hold on??? If I get sick, can I recover with meds? Evidence in mouse trials suggests: yes!”

The first dose

I shook many hands at the CHDI meeting – perhaps even the hands of those who will produce the first effective treatment to stop HD symptoms.

After the conference, we have all returned to the HD trenches.

The scientists must now turn hope into actual treatments.

I must continue my work as an advocate for the Huntington’s Disease Society of America (HDSA).

My task is to carry the message of hope of a treatment to everybody I encounter in the HD community, either in person or online.

Indeed, this must become the priority of HDSA and advocates everywhere.

In an HD treatment, the first dose is hope.

Gene Veritas and CHDI's newly launched logo. Dr. Simon Noble, CHDI’s director of scientific communications, explained to the audience that the new logo symbolizes CHDI as a “drug development organization” seeking “effective treatments” as its first goal. The tree represents the biology and chemistry involved in HD and HD research, clinical developments, neurons, biological pathways, and the hereditary nature of HD. The logo's muted color reflects the “somber nature” of CHDI’s mission. While the initials “CHDI” once referred to “cure Huntington’s disease initiative,” the foundation emphasizes that the initials no longer signify that phrase. "We can worry about curing down the line, however you want to define curing," Dr. Noble stated. (photo by Lev Blumenstein)

(In a future article I will examine the research progress reported at the CHDI conference.)

Top researcher: ‘Genuine optimism’ about treatments for Huntington’s disease

With several potential treatments heading for clinical trials, the head researcher of the so-called “cure Huntington’s initiative” feels “genuine optimism” about alleviating the devastating symptoms of this incurable, fatal brain disorder that also affects other areas of the body.

“People ask me all the time, ‘Are you optimistic?’” said Dr. Robert Pacifici, the chief scientific officer of CHDI Management, Inc., the virtual biotech firm dedicated exclusively to ending HD. “I am. I really am. I’m genuinely optimistic.”

CHDI Management is the research arm of the CHDI Foundation, Inc., the multi-million-dollar initiative backed by a group of anonymous donors.

Dr. Pacifici made his comments in an interview with me during CHDI’s 7th Annual HD Therapeutics Conference at the Parker Palm Springs hotel in Palm Springs, CA, February 27-March 1.

Representing both academia and drug companies, the approximately 200 scientists and observers at the conference were abuzz with the promising developments presented by their colleagues in the formal part of the program.

When he expresses optimism, Dr. Pacifici told me, “the HD community doesn’t let you get off easy. They say, ‘Why?”

He outlined three major reasons for his optimism.

First, CHDI and the HD research community have “a large number of shots on goal” in terms of potential treatments.

“There are now eight things with the potential to reach the clinic in a two-year time horizon and a bunch more behind that,” Dr. Pacifici said.

(Scientists do not predict the outcomeof trials nor the date at which an effective treatment will be found.)

Secondly, he stated that researchers will test each compound under study so as to obtain “an unambiguous result.” This will permit the researchers to quickly evaluate the results and, if necessary, adjust the compounds.

Third, Dr. Pacifici pointed out that the potential treatments are “custom-crafted” for Huntington’s disease.

Researchers know that potential drugs must to enter the brain, be taken for a long time, and not present serious negative side effects, he explained. By making the drugs HD-specific, the researchers can meet these challenges.

Future articles will explore the results of the conference and specific treatments in greater detail.

You can my watch the interview with Dr. Pacifici in the video below. Also visit www.hdbuzz.net.

It’s time for the Huntington’s community to speak out – and HDSA is listening

The HD community has a golden opportunity to both strengthen and shape the future of the Huntington’s Disease Society of America (HDSA) and its mission of care and cure – a mission that some grassroots advocates have seen as not fully encompassing their concerns and struggles.

With a deadline of February 24, a task force of the HDSA Board of Trustees seeks feedback on a proposed strategic plan for the years 2012-2016.

“Before the Plan is finalized and implemented, we want to receive input from all interested members of the community,” HDSA CEO Louise Vetter wrote in a letter posted on the HDSA website. The letter contains a link to the plan. A feedback form is located at the end of the letter. Click here to read the letter.

“The Strategic Planning Task Force spent hundreds of hours over 18 months conducting data review, community surveys, and holding discussions with individuals from every constituency of the HD community,” Vetter stated in the letter. “They used this information to assess the business of HDSA and develop this Plan for the growth of the Society, so that we can provide more services to families affected by HD and fund more research that can improve our knowledge base on HD and therefore lead us closer to effective therapeutic interventions.”

The task force included Vetter, HDSA Board of Trustees Chairman Donald Barr, and four other board members.

HDSA CEO Louise Vetter and Board of Trustees Chairman Donald Barr (photo by Gene Veritas)

As the 2011 HDSA Person of the Year and a former board member of the San Diego chapter, I urge everybody in the HD community to become familiar with the plan and provide comments. While the Board of Trustees and the HDSA professional staff in New York City perform key leadership functions, the chapters and volunteers are the lifeblood of the organization.

We are HDSA, and it’s up to us make our voices heard.

Below I present an outline of the plan as well as my own suggestions for improving it.

Plan introduction: balancing care and cure

The first eight pages of the 39-page document provide an overview of HDSA’s values, mission, and community.

As the document states, the organization’s last strategic review took place in 1998 – well before dramatic advances in both communications and science. Since then, scientists have come much closer to understanding HD. We now stand on the verge of revolutionary clinical trials.

It’s important to point out that the CHDI Foundation, Inc., the so-called “cure HD initiative,” which spent approximately $100 million in 2011 and has a far more narrow focus than HDSA, has emerged as the non-governmental sector leader in developing potential treatments (click here to read more).

HDSA’s current budget is approximately $8.5 million. According to the 2009-2010 annual report, 26 percent of the budget went to family services, 20 percent to fundraising, 20 percent to chapter development, 17 percent to education, ten percent to management and general expenses, and just seven percent for research.

Those amounts are a far cry from the early 2000s, when HDSA annually spent millions on research.

Vetter told me in an interview in May 2011 that HDSA will strive to increase its budget to as much as $20 million. For now, however, the proposed strategic plan aims for more modest annual increases of five percent, with a goal of raising $10.2 million in 2016.

Despite CHDI’s massive investment in research, the HDSA plan proposes a continued commitment to both “care” (services, education, and advocacy) and “cure” (research). As I discuss below, HDSA aims to launch a new research program, which would complement research done by CHDI and also the Hereditary Disease Foundation (HDF).

I agree that HDSA should continue to sponsor research, but I believe it should also invest more in other areas.

In the past, HDSA has primarily supported basic research, that is, research that leads to a deeper understanding of the disease but not necessarily to immediate application as a treatment or cure. CHDI now focuses on what is called the “treatment pipeline,” the search for ways to delay or halt the progression of HD using the knowledge of basic research created by others but also through its own projects.

Of course, in this fast-paced era of biotechnology, the line between basic and applied research has becoming increasingly blurred. Frequently, scientists can quickly turn new basic knowledge into a strategy for a treatment or cure. In this respect, the HDSA plan for continued research makes sense. CHDI and the HDF will continue to perform the bulk of the research, but HDSA-sponsored research will likely turn up new clues and perhaps even potential treatments.

The more brains we have working on treatments and a cure, the better our chances of success.

A community service organization

Crucially, the strategic plan recognizes the key part played by HDSA’s 21 Centers of Excellence in providing assistance to HD patients and their families and serving as a focus for patient research and clinical trials. The creation of the Centers has given greater visibility and some additional funding to local HD clinics around the country, practically all of them associated with universities. Annually the Centers each receive about $50,000 in support from HDSA.

“The Society will seek to enhance the Centers’ role in clinical research by creating linkages with the new research program,” the document states. “Imagine if a basic scientist who was used to testing hypotheses in mice could finally test a theory on human blood samples made possible by a Center of Excellence?”

The plan involves expanding “care” from “family” services to “community” services.

“HDSA is committed to offering programs that can have the broadest impact and affect the most lives,” the document states.

The meaning of expanded care

In my opinion, the shift in emphasis from “family” to “community” stands out as the most important aspect of the plan. In light of CHDI’s emergence, I believe that HDSA can best support the cause by focusing on services to HD families, raising awareness, and recruiting individuals for research studies and clinical trials.

Indeed, the second part of the plan (pages 9-13), which outlines the seven major goals of the strategy, begins with “Goal I: Build an HD Community-service organization.”

To achieve this goal, the document sets forth four “core strategies”: 1) expanding access to clinical care; 2) enhancing social services and support resources; 3) improving access to long-term care facilities skilled in HD; and 4) increasing access to counseling.

To implement these goals, the plan proposes a series of actions. I’d emphasize two: the strengthening of the Centers of Excellence and the “development of a regional network of social workers to augment the existing National and Field-based social workers.”

The staffs of the Centers and social workers regularly come into close contact with the patients and their families. They provide the vital services and first-hand information that families so desperately need in the fight against HD. And, as HDSA recognizes, the Centers stand in the best position to help implement clinical trials.

The next six goals support the idea of community service: support of HD research, removing barriers to quality care (legislative advocacy), communication, expansion of the volunteer base (click here to read my previous analysis of this question), operating in a fiscally sound manner, and fundraising.

Trying too hard to catch up on research?

Despite the emphasis on community service and the clear movement away from pitting care against cure, the document left me with the strong impression that the task force has thought more about questions of research and less about other organizational needs such as advocacy and volunteer recruitment.

While the task force established yearly goals for all seven of the major strategic goals, it included an appendix only for research – a three-page synopsis of an HDSA research planning meeting held in April 2011. In this section (pages 37-39), I could sense the renewed commitment of HDSA to make a difference in HD research.

There and elsewhere in the plan, the task force mentioned the need to hire a “medical-scientific director to oversee and coordinate research programs.” The director would help lead HDSA’s efforts to educate the community about the importance of clinical trials and “deepen our partnerships” with other organizations seeking treatments and a cure.

The plan seems solid, in part because it gives the medical-scientific director the task of education on clinical trials.

Furthermore, the document reveals that the national board aims to end a difficult situation of delinquent payments to researchers – a situation that practically brought the Coalition for the Cure research program to a halt. According to the 2009-2010 annual report, the seven percent of the budget that backed research amounted to just $370,000. In informal conversations, I have heard that HDSA spent practically nothing on research in 2011.

Fortunately, CHDI’s large investment in research has counterbalanced HDSA’s diminished role.

However, precisely because of CHDI’s huge role in research, grassroots volunteers might wonder why other areas of the strategic plan did not receive a more detailed plan of action, not to mention the possibility of hiring, when possible, additional specialized personnel in areas such as advocacy and volunteer recruitment.

Local needs

As I wrote previously, “I believe it’s implicit that the chapters and volunteers, as usual, will need to take the initiative locally” with respect to volunteer recruitment and other activities.

To cite just two examples of local need: HDSA should increase funding to Centers of Excellence for programming and staffing, and the all-volunteer chapters could also benefit greatly from increased clerical and other paid staff support.

As someone who came to HDSA through a support group, I would have liked to see a more detailed discussion of these groups’ importance.

I agree with the plan’s assertion that “personalized support, like financial aid or case management, for every family facing HD is not realistic for the Society given our budget.” Nevertheless, I definitely believe that, along with our families, HDSA should brainstorm on how to help relieve the tremendous and often financially crippling care burden of HD. One possibility frequently mentioned in HD Facebook discussions involves support for local, private assistance initiatives. HDSA could partner with these initiatives and help raise their profile.

As a disease community, we need to become more creative in these areas – including better information for families seeking specialized nursing home care for their loved ones.

Communications and advocacy

I believe that the plan overreaches by aiming to make HDSA the “premier communicator of HD information.”

The community obtains information from a wide variety of sources. Hundreds (if not thousands) of families rely on HD Facebook communities and other sources of HD news. So far, HDSA’s presence on Facebook is limited, although the strategic plan briefly mentions the need to expand the use of the social media for advocacy and fundraising. HDSA might also promote a communications network in which it can play a key coordinating role.

In conjunction, it could form a kind of “HD news service” in which volunteers could report on HD issues in their local communities and share news items and articles with the national organization.

While HDSA has made important strides in advocacy, I believe the organization should invest even more in this area and assure long-term continuity of specific programs and initiatives. In recent decades, the organization has too often started from scratch, leaving the volunteer base confused and making advocacy inefficient. The organization also should promote greater awareness of the history of HDSA as an entity founded by a great HD advocate – Marjorie Guthrie – and partly dedicated to the memory of another great advocate of humanity – her husband Woody Guthrie.

Optimism – if we participate

I am optimistic that HDSA can reach these many goals and inspire people to become active.

We need to keep in mind that HDSA has limited resources – but also that, ultimately, we grassroots activists, volunteers, support group members, chapter board members, relatives, friends, and supporters are the organization’s most important resource.

To its credit, the HDSA Strategic Planning Task Force has defined its plan as an “active, living document” to be “reviewed regularly to revisit timelines, push progress and help the Society evaluate opportunities.”

Let’s not pass up this unique opportunity to express our opinions and make a real difference in the future of HDSA.

***
In my previous article, I mentioned that the A Physician’s Guide to the Management of Huntington’s Disease was not available online. HDSA will put the guide online following the 2012 national convention, June 8-10, in Las Vegas.

The quandary of denial in the Huntington’s disease community (Part II)

The fear of confronting the devastating, incurable, and ultimately deadly symptoms of Huntington’s disease, coupled with its terrible stigma, causes many in the HD community to go into denial. They avoid participation in research trials and other activities crucial for combating the disorder.

In Part I of this two-part series, I revealed how my own family’s struggles with HD highlight how denial hampers involvement (click here to read more).

“How do we untie this terribly complex knot of denial?” I asked. “I am in a quandary about how to act – and to overcome this problem that threatens our march to treatments and a cure.”

Here I propose some practical strategies for overcoming denial at the level of the individual, the family, and the larger HD community, including both physicians and the main organization that cares for HD families.

The struggle within

The fight against denial and for participation begins within us.

In the words of Dr. LaVonne Goodman, the founder of Huntington’s Disease Drug Works and physician to several dozen HD patients, we in the HD community “suffer not just from society and intra-family struggle – but also from internalized stigma that we have ‘learned’ from others, and incorporated into self.”

We need to block this internalized stigma from leading us into denial and preventing us from fighting both the disease and the external stigma.

Dr. LaVonne Goodman (photo by Gene Veritas)

On January 30, Dr. Goodman published a detailed article that identifies stigma as an actual “component of Huntington’s disease.”

“Stigma drives HD families into the closet where we suffer as a marginalized part of society,” Dr. Goodman wrote. “Further, the fear of stigma likely prevents those with early disease from seeking medical care, as it does with mental illness or from signing up for clinical trials. Study has shown that when society becomes aware of HD family status, individuals can experience discrimination in employment, housing, medical care and social relationships. Stigma is damaging even before clinical diagnosis, negatively affecting the quality of life for these individuals and their loved ones.”

Dr. Goodman’s article is a must-read for the entire HD community.

Why care?

We must always remember that we each have an individual responsibility in fighting HD and making others aware of our plight.

“If we don’t speak up for ourselves, why should anybody care about us?” Bill Johnston, the public relations director of the San Diego Chargers and the husband of an HD patient, once told the San Diego support group.

Exercising the power of our own voices helps rebuild our self-esteem, so easily wounded by the depressing symptoms of HD and the terrible stigma. It also builds badly needed awareness about a disease still largely unknown to the public.

Bill Johnston carrying the Olympic in 2002 to raise HD awareness (photo by Mike Nowak)

Renewed participation

While we cannot force people to come to terms with their denial and join the cause, we can set an example by daily renewing our own commitment to participate.

That commitment can include attending a support group or volunteering for the local chapter or affiliate of the Huntington’s Disease Society of America (HDSA). (Many other countries have their own HD organizations; click here to learn more.)

HDSA chapters need people to help with so much: fundraisers, advocacy, communications and media contacts, support groups, the Centers of Excellence for Family Services and Research, volunteer recruitment, education and awareness-building, and “diplomats” to provide information about clinical trials. No prior experience is necessary, and individuals of all ages and skill sets can pitch in.

Helping shape HDSA: you have till Feb. 24

In recent years, HDSA has experienced a financial and organizational crisis, and some members of the HD community have criticized it for an apparent lack of concern about the problems of the everyday HD family.

HDSA recognizes such complaints and aims to be more responsive. HDSA CEO Louise Vetter and the national board of directors want the HD community’s feedback on a proposed five-year strategy for increasing the size, reach, and impact of the organization.

You can find the link to the proposal and read Vetter’s letter soliciting input from the HD community by clicking here. The deadline for comments is February 24, 2012.

Bolstering HDSA, breaking denial

In my next article, I will comment in detail on the HDSA plan. Here I want to highlight the HDSA goal of bringing “new folks into our fight” through an increase in the number of volunteers.

“Many organizations for diseases as rare as HD are many times our size,” the proposal states. “It is imperative that we increase our capacity so that we can do more, fund more research and accelerate the accomplishment of our vision – a world free of HD.”

HDSA wants to train and “deploy an ‘army of HD’ers’ to give voice and action to HD causes and needs.” To do so, over the next five year HDSA aims to increase the number of chapters and affiliates from 45 to 55. It also aims to add at least 200 new volunteers per year. The plan states that HDSA will support the volunteer base “with resources,” presumably in the form of dollars and staff support.

The plan doesn’t specify exactly how HDSA will reach these goals. I believe it’s implicit that the chapters and volunteers, as usual, will need to take the initiative locally.

Nevertheless, the national board recognizes the need to restore some confidence lost in recent years. It wants to improve the bonds between the national office and the chapters and affiliates. Specifically, it proposes “to build a strong, ongoing dialogue … that fosters a ‘we’ and not ‘us vs. them.’”

By including input from the community and emphasizing dialogue, the planning process presents a golden opportunity for the HD community to both strengthen and shape the future of HDSA and its mission of care and cure.

By bolstering HDSA, we can help encourage the inactive members of our community to break through their denial.

Young people facing HD can also join the recently launched Huntington’s Disease Youth Organization.

The doctor’s impartial role

Breaking down denial requires education about the causes and symptoms of HD, genetic testing and discrimination, family planning, medical care and caregiving, and a wide range of other factors.

The educators in this process are multiple: HDSA, the Centers of Excellence, the support groups, the various HD Facebook groups and other web-based initiatives, social workers, genetic counselors, psychologists, and, most importantly, doctors and other medical personnel.

A doctor is often the first person to assist an individual or family confronting the onset of symptoms or learning about the disease for the first time.

Doctors, probably more than anybody else, can provide hope.

And they can prevent people from going into denial. People respect doctors, and doctors provide an impartial assessment of a person’s medical condition. People are much more likely to listen to a physician than a family member or activist with whom they’ve tangled over HD.

So, doctors need to be properly informed about HD.

A helpful guide

HD specialists and neurologists familiar with HD can skillfully diagnose, treat, and counsel HD people. However, because HD patients form a relatively small group (an estimated 30,000 individuals in the U.S.), most doctors know little, if anything, about the disease.

HDSA has sought to educate doctors about HD by publishing A Physician’s Guide to the Management of Huntington’s Disease, now in its third edition (2011). Authored by four respected HD specialists, the guide provides an overview of HD symptoms, genetic counseling and testing, treatment and care, juvenile HD, management of late-stage HD, and HD research and clinical trials.

Written in a non-technical style, the guide is an invaluable tool to educate the public.

A free flow of information

HDSA provides free copies of the print guide. However, it limits them to one per family.

Furthermore, the publication is not available online, because HDSA aims to track the physicians requesting the publication as part of the HD educational process.

A number of people in the HD community believe that HDSA should make the guide available as a downloadable PDF. Indeed, some are puzzled that, in the era of the Internet and the e-book, HDSA has not facilitated access to the publication.


I have participated in many conversations about HD on Facebook in which people ask very basic questions about HD, as well as sophisticated ones about medical matters. It would be enormously helpful to point to the document online.

In visits to my primary care doctor for non-HD matters, I’ve noted how he relies heavily on not just the health plan’s computer network, but the wider web.

Imagine a doctor seeing his or her first HD patient who has to call HDSA for a copy of the guide rather than download it.

The freer the flow of high-quality, doctor-generated information about HD, the greater our chances at ending stigma and denial.

(In a future article I will review the Physician’s Guide.)

Increasing visibility

Because doctors form the front line of diagnosis and treatment, we in the HD community must advocate the bolstering of the HDSA Centers of Excellence, support groups, and HD educational events such as the annual convention of the Northern California chapter.

We also need to participate in HDSA walks and other fundraisers that emphasize raising awareness among the general public. These events may not raise as much money as galas or other big events, but they provide a huge symbolic impact in the local community.

The more visible we can make HD in the local community, the greater the chance someone in denial might be brought to reflect on his or her predicament and the effort to defeat HD.

Then we can build a stronger movement and take one step closer to the goal we all strive for: the end of HD.

The quandary of denial in the Huntington’s disease community (Part I)

The natural human tendency toward denial presents one of the biggest obstacles to strengthening the Huntington’s disease movement, including the recruitment of individuals for the observational studies and clinical trials crucial for developing effective treatments and a cure.

How do we more proactive members of the HD community influence those living in denial? How do we convince them that they need to inform themselves about HD and join the effort to defeat it?

I have wrestled with these important questions, as well as my own multiple forms of denial, ever since learning in late 1995 that my mother had HD and that I had a 50-50 chance of inheriting the condition. My denial, and feelings about others’ denial, became dreadfully more complex after I tested positive for HD in 1999.

I remained deeply in the “HD closet” for many years because of the fear of genetic discrimination, but became vocal via this pseudonymous blog. In mid-2010, I began to speak publicly about my condition.

A year ago, I “unmasked Gene Veritas” and revealed my story to some 250 prominent scientists and other observers at the Sixth Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc., informally known as the “cure Huntington’s disease initiative.” I made other presentations at my local support group, an HDSA chapter convention, a pharmaceutical company aiming for a revolutionary clinical trial, and a symposium on clinical trials.

Now I want to tackle the problem of denial head-on.

Yes, we rely on denial to face the daily fear of HD symptoms, as well as the stigma accompanying the condition, but we ultimately must overcome it if we are to win the battle against HD.

And, yes, each family situation differs. In some cases, it may be easier than others. But by looking at my own family as an example, I aim to analyze some of the causes of denial, how it plays out in HD families, and how it maintains its insidious grip.

A powerful firewall

Denial often shadows my family life.

Despite my dramatic exit from the HD closet, I continue to maintain a firewall between, on the one hand, my HD activism and, on the other, the workplace and my neighborhood.

I would like to break down the neighborhood barrier, but my wife, who has lovingly stood by me through the entire trauma of the HD experience, has resisted the idea of expanding my advocacy beyond the HD community

After being named the 2011 Person of the Year of the Huntington’s Disease Society of America (HDSA) last June (click here to read more), I wanted to solicit an article in the community newspaper as a way to build awareness and support for HDSA locally. I hoped the prestige could help take my advocacy to a new level.

My wife said no. “I don’t want this in our house,” she stated adamantly, referring to HD and all of its implications, including the impact such a newspaper article might have on our daughter, now in her first year of middle school.

My daughter knows that I am gene-positive and that she tested negative in the womb, and she even has read some of my blog articles. However, my wife does not want to see her constantly exposed to HD, and she wants her to enjoy her final moments of childhood without having to worry about my health and the future impact on the family of HD when my inevitable symptoms begin.

I respected my wife’s wishes – I know she will shoulder the burdens of HD in the long run – but I was deeply frustrated. “This is such a HUGE accomplishment in my life,” I wrote in my blog notes at the time. “The greatest recognition I have received to this point – one that is about changing the world. And I can’t celebrate it!! Because of the stigma. I need to talk more, get HD out there more.”

My wife initially didn’t want to display my HDSA award plaque in our hallway of family photos, but she later changed her mind.

A bittersweet award

I wrote in my notes:

I will show plaque to [my daughter]. Families that deal with [HD] naturally and up front are the ones that have the best outcome in the long run. Denial necessary in life, but when carried to extremes, or used as the main way of dealing with life…. It becomes harmful/pernicious.

Nothing is ever simple with HD! This just can’t be a great award. [Instead] it’s got to be a reminder of my situation – and of our entire community’s situation.

Ends up being bittersweet.

If it were any other award, we’d be celebrating. No celebration. No mention. No discussion.

I hate denial!

‘Mental problems’

The HD community is filled with sad stories about denial among family members. People from HD families viscerally bond regarding the feelings of frustration, hurt, and anger over relatives’ denial.

My mother’s brother and his wife hid Huntington’s from their two children and their spouses. They explained away my mother’s behavior as “mental problems” (click here to read more). Only in the days before my mother died – six years ago this month – did my aunt tell my cousins the real cause. My cousins weren’t close to my family, but at the wake they were still so shocked by the news of HD that they cried much more than my sister, my father, and I.

Over the years I nudged my uncle, a successful small businessman and active in his community, to join the cause against HD. Many years ago, before my mother’s death, I wrote him a long and heartfelt letter outlining ways to help.

I never got a response.

To this day, I don’t know if he ever tested for HD. In his mid-70s, he has apparently showed no symptoms. Out of sight, out of mind, perhaps.

Jealousy over testing

For more than a decade, I have clashed with my sister and her family over their own denial, lack of involvement with my parents, and refusal to join the cause (click here to read more).

My sister, who to my knowledge remains untested, had her three sons before we learned of HD. Although we have never discussed it, she has undoubtedly agonized about whether she inherited the gene and, worst of all, passed it on.

She became extremely jealous of my wife and me for two big reasons: we had a daughter, and our child had tested negative.

Around that time, in 2001, my sister started to cut herself and her family off from me and my family.

Isolation

I tried to keep in contact, but she showed little interest in learning more about HD. While I have long taken doctor-approved supplements and lived with the hope that treatments could save me from developing symptoms, from what I can tell, she has chosen not to learn about such potential solutions.

As my mother declined, although I lived thousands of miles away in California, I strived to find a good care regimen for her and to assist my father with suggestions and gentle exhortations. My sister, who lived only a couple miles away in Ohio, would visit my parents but took very little initiative to improve their situation.

She became angry and resentful about my offers of assistance and suggestions. I grew increasingly frustrated with the lack of communication with the family member geographically and personally closest to my parents.

In the midst of our family’s increasing difficulties with my mother’s condition, my sister told me on the phone, “You’re not really a brother.”

I was stunned, perplexed, and offended. I had traveled regularly to my hometown to visit not just my parents, but my sister, her husband, and my three nephews. My wife and I had also offered to fly out my oldest nephew to San Diego and take him to Disneyland, Sea World, the San Diego Zoo, and other California attractions, but my sister never responded.

Failed communication

In 2005, after several years without speaking, I insisted that we reestablish communication to help my father admit my mother to a nursing home. We became close again during the final months of our mother’s life and, when she died, my sister planned the wake and funeral so that my wife, daughter, and I could fly out in time.

However, as my father rapidly declined in the wake of my mother’s death, my sister and I again disagreed about a plan of care for him. When dialogue became impossible, I asked my father’s attorney to serve as an intermediary and to assist her with his affairs, including the transition to a memory care unit in an assisted living facility.

My father died in September 2009. I learned of his death in an e-mail from the lawyer after I participated in an intense, day-long HD observational study. However, my sister did not delay the funeral, making it practically impossible to get to Ohio on time. (Click here to read more.)

I was so distraught about the situation that I also concluded I might suffer a heart attack if I attempted to attend the funeral. I organized a private memorial service for my father at our San Diego home.

I have not spoken to my sister since August 2008. In 2010 we both attended a memorial luncheon for a deceased aunt, but we did not speak or even acknowledge each other’s presence. I was still livid about her lack of compassion in failing to delay my father’s funeral so that I might participate.

Keeping a distance

At this point, the anger and resentment are so deep that I believe my sister and I may never speak again.

While I have fought to combat HD, my sister has preferred to ignore it. That has compounded the kind of intense family disagreements that sometimes accompany inevitable life-and-death issues.

After so many failed attempts at establishing a relationship with my sister, I have concluded that, because of denial and other reasons, she and her family simply have no interest in me and my family. I concluded that it would be foolish to insist.

I am a firm believer in love as a solution to many of the world’s problems, including personal hatred and misunderstanding.

In my interpretation, love means keeping one’s distance from people who don’t want a relationship.

Advocacy in my home state

On May 14, I’m tentatively scheduled to speak on my experience with HD at an HDSA event in Northeast Ohio, where I grew up and where my parents are buried side by side.

Returning to my home state to speak out as an HDSA advocate will surely stir powerful and difficult emotions.

Many questions are running through my head. Should I invite my uncle and my sister – and their families – to attend? Would they even show up after so many years of conflict and denial? Would we talk and, if so, what would we say? Part of me doesn’t want them to attend, because I fear my anger at them might diminish the effectiveness of my activism.

Frankly, I don’t think they want to hear what I have to say, especially because I advocate activism. Years ago, my sister used to read at least some of my blog, but now I have no idea whether she follows it. I doubt my uncle even knows I have a blog. Should I continue to chalk them up as a lost cause? Or, in the name of the movement, should I make the extra effort to bring them into the cause?

As an advocate, I feel obliged to reach out. However, as a member of an HD family, I feel forlorn about the prospects for action by people such as my uncle and sister.

How to untie this knot?

I am reaping the fruits of my family’s long denial of HD.

The great irony is that my sister, my uncle, and their families probably don’t even know that I was named the HDSA Person of the Year.

The easy solution is to do nothing about the May event. Despite my award and my long years in the HD trenches, I feel powerless to change them.

My fellow HD activists, family members, and friends, what would you do?

How do we untie this terribly complex knot of denial?

I am in quandary about how to act – and to overcome this problem that threatens our march to treatments and a cure.

Continuing to speak out

Denial is like an added curse on HD families already so overwhelmed with the disease’s medical burdens.

My family’s story pales in comparison to other examples of denial and insensitivity.

As I reflect on these stories, I’m struck by the immensity of the stigma surrounding HD.

Perhaps I can take comfort in the fact that, no matter what my uncle or sister or anybody else thinks, I will speak out again about HD on May 14. In the final analysis, that is all I can do.

Someone will be listening, and that is good.

(Next: further reflections and concrete suggestions for overcoming denial.)

To strive or to chill? Seeking balance in the fight against Huntington’s disease

In late 1995, after I received the shocking news that my mother had Huntington’s disease, I decided to fight back for her by learning all that I could about this incurable disorder and also advocating for treatments and a cure.

Then, after testing positive for the HD gene in 1999, I sought to save myself by finding ways to stimulate my brain in order to stave off the inevitable neurological symptoms.

As I worked to maintain my health, my HD activism grew into a full, second career parallel to my professional work, and complicating my life as a husband and father.

Two views, two necessities

“Keep striving,” a close friend wrote recently after reading one of the articles in this blog, which, for seven years, has served as a chronicle of both my advocacy and strategies for avoiding HD and, in and of itself, has provided an escape valve for my frequent anxiety about the onset of symptoms (click here to read more).

I am living a very complex paradox. I must strive, but as I do, I also must avoid allowing my activism to exhaust me physically and emotionally.

As I wrote last year, I walk an HD tightrope that requires me to very judiciously balance all aspects of my life. One slip, and I could fall off the wire and plunge to disaster.

The past year has proved exhilarating but also psychologically trying, beginning with a major coming-out speech before world-renowned HD scientists last February and ending with wrenching articles about HD and suicide, abortion, and the deaths of two girls from juvenile HD.

“You need to chill more,” another close friend of 32 years has counseled me repeatedly throughout my journey with HD.

He recommends that I “chill” as an antidote to the striving. He recommends spending less time on work, writing, and the HD movement and more on the simple, relaxing things that I could enjoy: good food and wine, books, movies, conversation with friends, walks with the dog – or just plain doing nothing.

To strive or to chill? That’s the question I face each day.

The rhythm of life

In a memorable sermon during my college years, the pastor of St. Thomas More Chapel at Yale, Father Richard Russell, spoke of the need to “get into the rhythm of life.”

As an HD activist, I especially feel that need. When I achieve that rhythm, my existence feels like the alternating phases of the heart’s cycle – pumping and relaxing over and over again.

Over the past day, that’s exactly how I’ve approached HD and the rest of my life.

This past Saturday afternoon, my wife, our 11-year-old daughter, and I took an hour-long walk in the San Diego beach community of Pacific Beach. Couples and families like us strolled, while more adventurous people on bikes or roller skates weaved in and out. The 70-degree sun bathed us all. We dined on Greek fare at our favorite restaurant, followed by frozen yogurt.

Late at night I worked on this article. This weekend, I had consciously chosen not to write on a difficult topic. I wanted to “chill.”

While I wrote, I couldn’t forget how during the previous night I chatted on Facebook for an hour, trying to help a person recently shocked by the revelation of HD in her large, extended family.

Last night I turned off the computer without finishing the article. I read for a while before turning in.

This morning, I walked door-to-door with my daughter as she sold Girl Scout cookies in the neighborhood.

What a great feeling! Watching her take charge of the sales, I recognized how much more mature and confident she has become.

I forgot not only about HD, but all my other cares.

Now, after lunch, I sit again at the computer, contemplating how I must stay in the rhythm and find the right balance between striving and chilling.

Enjoying the ride

It’s nerve-wracking to wait and wonder when and how the individual symptoms will start, especially because, at 52, I have reached the age at which my mother had already developed symptoms.

I sometimes become impatient about the rate of progress towards treatments and a potential cure.

Sometimes my fear provokes megalomaniacal thoughts about striving against HD, as if I’m a lone knight battling a fire-breathing dragon.

Then I remind myself that I cannot singlehandedly defeat this disease.

We all must get into the rhythm together: patients, asymptomatic gene-positive individuals like me, caregivers, physicians, and researchers.

And we all need to take a break from striving in order to chill.

As one of my California HD Facebook friends likes to say: when matters get rough, “go surfing!”

I don’t surf, but the thought of the power, immensity, and majesty of the ocean brings home the point: I control only a very small part of my destiny, and I might as well enjoy my ride on earth.

Advocacy pays off: Huntington’s disease stem-cell research advances in California

Grass-roots advocacy for Huntington’s disease stem-cell research is paying off.

Using funds from the state of California secured with the help of advocates, leading HD stem-cell scientists are taking important steps towards developing potential ways to treat, reverse, and perhaps even cure HD.

These funds come from the California Institute for Regenerative Medicine (CIRM), the $3 billion initiative approved by the state’s voters in November 2004 to establish grants and loans for stem-cell research aimed at rapidly developing treatments for a host of diseases.

Leading stem-cell advocates had successfully worked to get the measure on the ballot as a state initiative after President George W. Bush had signed an order blocking the establishment of new human embryonic stem-cell lines, which scientists needed to expand research in the field. President Barack Obama later rescinded that order.

CIRM projects have spurred the creation of new embryonic stem-cell research, as well as other kinds of stem cells.

Millions in funding

While the CIRM oversight board has representatives concerned with Alzheimer’s disease and diabetes, among other conditions, it has no representative from the Huntington’s disease community.

Nevertheless, in 2007, as CIRM prepared to award its first research grants, California’s grass-roots HD activists began campaigning for the board to address Huntington’s stem-cell projects.

In October of that year, I arranged for Bill Johnston, the public relations director of the San Diego Chargers and the president of the San Diego Chapter of the Huntington’s Disease Society of America, to appeal to the oversight board during a public meeting in San Diego. As he spoke, Johnston held his wife Ramona, who has HD. This was the very first time that a member of the HD community had appeared before the board.

I also spearheaded the organization of the December 2007 CIRM “Spotlight on Huntington’s Disease,” held at the University of California, Los Angeles. The presentation included talks by two leading scientists, as well as a plea for HD research from activist Frances Saldaña and her daughter Margie Hayes, one of three siblings who developed juvenile HD and the mother of two at-risk children. (For more on these first meetings, click here.)

As mother Frances Saldaña (left) looks on, Margie Hayes tells about her struggle against HD at the CIRM Spotlight on Huntington's Disease, Los Angeles, December 12, 2007 (photo by Gene Veritas).

CIRM President Dr. Alan Trounson (left) with Alexa Shaffer and mother Sharon. Sharon has HD, and Alexa is at risk. They told their stories at a CIRM board meeting in San Diego on September 25, 2008 (photo by Gene Veritas).

Advocates throughout California joined hands in this cause, with other HD family members speaking before the oversight board at its regular public meetings in different parts of the state. (For the sake of brevity, I won’t list the names of the numerous dedicated individuals involved in these efforts.)

Together with the researchers’ meticulously prepared grant applications, this advocacy has generated solid results: to date, HD stem-cell research projects, based mainly at the University of California, Davis (UC Davis), and the University of California, Irvine (UCI), have received $7.9 million in CIRM funding.

Striving for an HD ‘Disease Team’

Tomorrow, January 24, Jan Nolta, Ph.D., the director of the UC Davis Institute for Regenerative Cures, will submit an application to CIRM for a $20 million project to fund an HD “Disease Team.” The team will aim to develop the very first human clinical trial for an HD stem-cell treatment, which would involve attacking the disease at its genetic roots and infusing the brain with an important growth factor known as BDNF.

Just last month, Dr. Nolta published a scientific article demonstrating promising results in pre-clinical experiments, which must precede human trials (click here to read more).

Dr. Nolta uses a well-known type of stem cells, called “mesenchymal stem cells.” A long-time expert on these cells, Dr. Nolta refers to them as “paramedics” because of the way they congregate around and repair damaged cells.

Dr. Nolta at the HD bench at the Institute for Regenerative Cures (photo by Gene Veritas)

Last May I spent a day interviewing Dr. Nolta and observing the work of the UC Davis institute, co-founded by the university and CIRM (click here to read more about my visit and Dr. Nolta’s work).

Once again, we will mobilize our California network of advocates, this time in support of the HD Disease Team application. We want to stress the urgency of finding treatments for this killer disease and the importance of HD research in advancing the stem-cell field.

New stem-cell lines

At UCI, HD stem-cell research has progressed rapidly under the leadership of Dr. Leslie Thompson, a professor in the UCI School of Medicine’s Departments of Psychiatry and Human Behavior, the interim director of the Center for Mitochondrial and Molecular Medicine and Genetics, and a holder of various other positions within the university.

With one CIRM grant of $900,000, awarded in 2008, Dr. Thompson and her researchers are creating new neuronal (brain) stem cells. They produce these cells by taking skin-cell samples from both HD-affected and non-HD people, “reprogramming” them to become stem cells, and then “differentiating” them into the neuronal stem cells.

From these new cells, they eventually hope to obtain medium spiny neurons, the kind of brain cell most affected by HD. The disease occurs because these cells malfunction, become damaged, and die. Using the neuronal stem cells, the research team can study HD at work in a live, real-time human setting.

This grant also funds research on human stem cells taken from embryos discarded by couples who underwent PGD (preimplantation genetic diagnosis) in order to have HD-free children. In this project, Dr. Thompson and her researchers have succeeded in establishing one new line of human embryonic stem cells, which will be used to study HD.

Announced in late 2010, a second CIRM grant of $3.8 million funds a UCI project that seeks to develop a stem-cell treatment for study in HD mice. The initial experiments in this project demonstrate that the mice’s symptoms improve after the introduction of mouse stem cells into their brains. The second stage is examining the effect of human stem cells on the mouse brains.

Later, Dr. Thompson hopes to apply for another HD Disease Team grant to develop ways to apply her research for potential stem-cell treatments in humans.

In future articles, I will explore in greater depth how Dr. Nolta’s and Dr. Thompson’s respective projects could lead to effective treatments.

The impact of our work

Interviewing Dr. Thompson in her office on January 20, I felt a deep sense of accomplishment.

In an instant, I felt as if time had fast-forwarded me from 2007, when she and I prepared intensely to organize the CIRM Spotlight on HD, to the present, when the results of the statewide advocacy efforts are blooming in the UCI labs.

I had advocated with and for Dr. Thompson, and now I was sitting across from her and hearing good news.

Dr. Thompson (left) with Frances Saldaña at the Huntington's Study Group meeting in San Diego, October 16, 2010 (photo by Gene Veritas)

In voting for the CIRM, and then advocating for specific HD projects, we had achieved a historic breakthrough for HD research.

In hearing Dr. Thompson discuss the establishment of a new stem-cell line from the PGD embryos, I felt how profoundly political our advocacy has been, and how it directly impacts the quest for treatments and a cure.

The moment was exhilarating.

Gene Veritas: Back when the big controversy was occurring, when Bush said, “No more new lines,” this is a --

Leslie Thompson: A new line.

GV: This is a new line that, thanks to the CIRM and the law in California, was supposed to occur.

LT: Thanks to the CIRM. Correct.

GV: So we’re seeing an actual impact of a political decision here to do something.

LT: Yes. All of it. All of [the stem-cell work]. Because we wouldn’t be able to do this work without CIRM funding.

We can all advocate for the cause

Advocacy is one of the biggest challenges for the HD movement. It demands long hours of preparation, the study of complex issues, networking, and efforts to gain access to public officials and other powerful individuals.

It also requires patience, dedication, and teamwork. We California advocates have recognized these requirements and tried our best to practice them.

On the stem-cell front, we have in our favor a great set of universities with top-flight scientists like Dr. Nolta and Dr. Thompson. Both are well-known in the HD community, and both dedicate time outside of work to supporting it. Dr. Thompson finds inspiration in HD families. A newcomer to HD research, Dr. Nolta took on this new field after coming into contact with the local HD medical specialist, Dr. Vicki Wheelock, and the community she serves.

Advocates and scientists have meshed well throughout the crusade for stem-cell treatments.

Finally, I believe our advocacy has proved effective because of the willingness of affected families to tell their stories in public – despite the pain or awkwardness it might cause – at CIRM meetings and to the doctors and physicians involved in HD research.

All of us in the HD community can become advocates. We need people to work on all levels – from meeting with government officials to writing letters. And we must always speak out.

You never know. Someone with the willingness and resources to help might just be listening. You can inspire that person to act.

(To learn more about California HD advocacy, please click here. To learn about national advocacy efforts, please click here.)

Let’s turn grief for ‘HD Angels’ into new impetus for the Huntington’s cure

The Huntington’s disease angels are sending us all an urgent message: we must redouble the effort to find effective treatments and a cure for this devil of a disease.

In the past few days, two more HD angels – children who have succumbed to this disease – have passed on.

On January 11, nine-year-old Kathleen Edward died while surrounded by loved ones in her Wyandotte, Michigan, home.

Kathleen and grandmother Rebecca (family photo)

On January 15 another child, twelve-year-old Olivia Ruggiano, died in Philadelphia.

While HD affects people of all ages, the ten percent of cases classified as juvenile Huntington’s disease (JHD) wrenchingly dramatize the disease’s crippling effect. Children and teenagers afflicted with JHD never experience a normal life. As in Kathleen’s and Olivia’s cases, some don’t even reach adulthood.

Together with Kathleen’s and Olivia’s families, the HD community grieves deeply: two young lives ended hopelessly.

Their deaths provide a startling reminder of the lack of treatments.

These HD angels want us all to cry out for increased funding for HD research – including the understudied juvenile onset – and a commitment from drug developers to broaden and speed up the search for treatments and a cure.

Two brave girls

In life, both Kathleen and Olivia had received an outpouring of sustenance from the HD community and beyond.

In 2010 a hateful neighbor, upset over a misunderstanding about a children’s birthday party, started feuding with Kathleen’s family. The neighbor bullied Kathleen on Facebook by posting a photo of the girl positioned over a set of crossbones. Another photo showed Kathleen’s HD-stricken mother in the arms of the Grim Reaper.

News coverage of the incident spurred donations to the family and expressions of support from around the world. Thanks to many generous individuals, Kathleen had the opportunity to go on a shopping spree – but only after first choosing gifts for her family members. (Click here to read more about this incident.)

“Olivia was a normal child who loved to wear frilly dresses with dirty knees while digging for worms,” Olivia’s mother Jennifer wrote on a fundraising site for the Delaware Valley Chapter of the Huntington’s Disease Society of America (HDSA). “Strong willed but always ready with a smile, giggle or hugs. She began showing developmental delays at 4 1/2, a slight lisp, uncoordinated, tripping a lot, dropping things.”

Olivia and friend at HDSA fundraising walk

“Then the focal seizures came, the first one being discovered the last day of day care before starting kindergarten,” Jennifer continued, referring to how Olivia would lean back and prop up her head, and then let her head drop into her lap. “We thought she was just being difficult or having selective hearing. Then they developed into stronger more intense seizures. Late in December 2007, right before Christmas she went into status (non-stop seizures).... Since then she has been on a spiral downhill.”

On a Facebook page titled “We All LOVE Olivia Ruggiano,” supporters and members of the HD community left Olivia a constant stream of encouraging messages as she struggled against the disease. Jennifer and other family members read the messages out loud to Olivia and, holding up a laptop, showed her the pictures people had posted.

Words of support

At Kathleen’s funeral on January 14, so many mourners turned out that the funeral home ran out of the flags fastened to cars in the procession to the cemetery, Rebecca told me via Facebook. Kathleen was buried next to her mother Laura Edward, who died of HD in 2009.

The Detroit Free Press ran two articles about Kathleen.

“Those who knew 9-year-old Kathleen Edward will never forget her infectious smile, one seen throughout her battle with juvenile Huntington’s disease,” one of the articles began.

The paper quoted grandmother Rebecca: “She suffered with this disease for a while, and she never complained,” Rebecca told the paper. “She was always happy, always smiling.”

You can watch a tribute to Kathleen in the video below.




After the two girls passed, scores of Facebook members expressed their condolences.

“We are all in mourning over Olivia leaving us,” one HD activist wrote on Olivia’s Facebook page. “Heaven is rejoicing to receive angel Olivia where she can be closer to everyone’s heart.”

“Know that we are with you in spirit,” another supporter wrote. “It’s going to be hard, but as Olivia was strong, you are also. Smile thru your tears. She is free. Love to all of you.”

News of the girls’ deaths and condolences also went out on other HD Facebook pages, including two dedicated to HD angels, Rebecca’s page, and Olivia’s mother’s page.

Viewing of Olivia will take place at Stolfo Funeral Home in Philadelphia 7-9 p.m. on January 19 and 8:30-10:30 a.m. on January 20, followed by a funeral Mass at 11 a.m. at Stella Maris Parish. In lieu of flowers the family requests donations be made to the Philly HERO Trust, P.O. Box 18008, Philadelphia, PA 19147.

Remembering the Ruggianos’ fight

In a phone conversation last night, Jennifer graciously recalled Olivia’s and her family’s fight against HD.

Jennifer started dating Ron Ruggiano in 1994, the same year his mother died of HD. Jennifer and Ron married in 1996.

As in many HD families, the disease was “a taboo subject in his family,” Jennifer said. But his mother’s death alerted Jennifer to the existence of the disease in the family. She contacted HDSA and learned what she could about the disorder, including the fact that a male could pass on a far worse form of the disease than he himself has.

Ron had not been tested for HD, so the couple knew that having gene-negative children was “a roll of the dice,” with a 50-50 chance of their children inheriting the defective gene, Jennifer recounted. In 1997 they had a daughter, Rania, who has not demonstrated symptoms of JHD (but has not been tested). Two years later, Olivia arrived.

Ron started to show the behavioral difficulties that often occur in the early stages of HD. In 2000, he was clinically diagnosed with the disease.

An astounding level of disease

On that fateful last day of daycare before kindergarten when Olivia had seizures, “she was speaking gibberish and not making any sense at all,” Jennifer remembered. “It just mushroomed from there. She was clumsy. She would fall down and trip a lot.”

Nevertheless, Olivia entered elementary school, where she participated in a small life skills class for the severely disabled. She stayed almost through the end of fifth grade.

Olivia (family photo)

“Sometimes she didn’t want to go to school,” Jennifer said, chuckling, “but she went. Sometimes she would fake her seizures. She was a smart little cookie.”

In 2007 both Olivia and her father finally underwent HD testing at Johns Hopkins University in Baltimore. Whereas a normal huntingtin gene has only ten to 29 repeats, Ron’s had 50 – ten repeats beyond the level that causes HD. Olivia had an astounding 109 repeats – a number that doomed her to childhood onset and an early death.

Olivia’s joys

Despite this terrible fate, Olivia strived to live like any child.

“She loved to dance,” Jennifer reminisced. “She loved to sing. She loved to watch musicals: of course, the Wizard of Oz, Grease, any kind of musical, Hairspray, all the Disney movies.”

Olivia also loved to help her mother cook and care for the home. She wouldn’t miss a chance to play in the pool at her cousin’s house or visit the New Jersey shore with her family.

Olivia was a “little devilish” in everything she did, Jennifer said. And she had a fascination with bugs. “She could spot an ant ten feet away,” Jennifer said, laughing.

With Ron unable to work, he received Social Security disability payments. Olivia further supported the family with her salary as a legal clerk in the Pennsylvania courts. A heavy emotional burden also fell onto Rania, as she watched her mother pay ever greater attention to Olivia.

The family dealt with HD as proactively as possible, Jennifer explained. In 2008 doctors gave Olivia a feeding tube to keep her properly nourished.

Meanwhile, in February 2010, Ron entered a nursing home, where, at 43, he struggles against HD.

A turn for the worse

Olivia’s health worsened dramatically in December 2010. She spent nearly the entire month hospitalized.

Just ten days after returning home, she developed an infection. “That’s when I made the decision not to take her back to the hospital,” Jennifer said. She decided that Olivia would live at home until she died.

Olivia continued to decline throughout 2011.

“She was on so many medications,” Jennifer recalled. “She was taking 40 milligrams of valium every four hours.”

Along with Olivia’s nurses, the family kept Olivia as comfortable as possible. On Thanksgiving Day, for example, they dressed her up in a pink dress and sweater and placed a pink flower in her hair. “Her nurses absolutely spoiled her,” Jennifer said.

Olivia at home on Thanksgiving Day, 2011 (family photo)

Olivia’s legacy

I asked Jennifer about Olivia’s legacy.

“She’s just another bright light,” she said, “another child that just fought … and fought … and fought.”

As an HD angel, Olivia will inspire others to fight – and will also contribute to the search for treatments and a cure. Months after undergoing genetic testing, both she and Ron donated cells for research. As Jennifer explained, researchers were able to make the cells from Olivia’s forearm reproduce and are hoping to induce them into becoming stem cells. Olivia’s cells could eventually end up in labs around the world that focus on developing treatments for HD.

Time for treatments

After learning about Kathleen and Olivia, my wife and I became saddened and distraught. Once again we relived the painful moments of 1999 and early 2000, when I tested positive for HD and we subsequently tested our daughter in the womb.

Our “miracle baby” tested negative, but had she inherited the HD gene, my wife would now face the terrible prospect of caring for two HD patients.

I became angry and depressed that HD had once again victimized families, and I feared that my own symptoms might start soon, leaving my unable to work and to enjoy my own family.

I also felt the urge to fight back.

“We must find treatments and a cure so that no more children suffer with Huntington’s disease,” I wrote on Olivia’s page.

The angels have fought bravely, but our community wearies as it sheds yet more tears of sorrow.

We need treatments now.