‘Predicting’ Huntington’s disease in the heartland

To develop treatments for a disease, researchers and physicians first need to understand how its symptoms evolve and how they affect people’s lives.

In early August, I traveled to the University of Iowa in Iowa City to donate blood, urine, and saliva samples, undergo a motor coordination exam and brain MRI scan, and perform a battery of cognitive and mood tests for the long-term research study Neurobiological Predictors of Huntington’s Disease, best known as PREDICT-HD, one of the largest public-private research projects in the history of the quest to defeat the disease.

My biological samples will become part of a bio-repository at the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH) located just outside Washington, D.C. Researchers from around the world can apply for access to these materials.

In studying gene-positive, asymptomatic people like me, the scores of researchers working at the University of Iowa, 26 other PREDICT centers in the U.S. and abroad, and many other institutions can try to analyze how the early symptoms of HD develop.

They are also seeking to identify HD “biomarkers” in the blood, cerebral spinal fluid (CSF), and brains of the study participants, who include formerly at-risk individuals who tested negative for HD. These individuals serve as a control, or comparison, group to ascertain which changes in the gene-positive people are specifically caused by HD.

Gene Veritas in preparation for PREDICT-HD MRI scan (photo by Sarah Petitt)

With biomarkers and other study data, researchers can effectively measure the effectiveness of potential treatments in upcoming clinical trials.

Patients: study us!

The lead scientist and administrator of the multi-million-dollar PREDICT study is Jane Paulsen, Ph.D., the co-director of the University of Iowa Huntington’s Disease Society of America Center of Excellence and Professor of Psychiatry, Neurology, Psychology, and Neuroscience. From 1991-96, she was a postdoctoral neuropsychology fellow at the University of California, San Diego (UCSD), where she directed the HD clinical research program and came into close contact with the local HD community.

“The desire to move towards earlier detection and identification was really brought forth at UCSD from the families,” Dr. Paulsen recalled in an August 6 interview. Such families, she noted, told her: “‘You know, I’ve been dealing with this for years, and it isn’t validated by the professional community. I don’t have a diagnosis. A lot of people just think I’m exaggerating.’

“So just that sense of so many people who are at risk, who might be having subtle symptoms. When we would see them, we could detect maybe cognitive or certainly emotional changes that might occur. There’s a lot of stages that occur before you get the motor signs and diagnosis.

“So the whole PREDICT project was sparked by families in San Diego saying, ‘I’ve seen this forever, and we need to detect it sooner, before I lose my job or blow up at my kids or I don’t take care of my home responsibilities the same or my friends don’t understand me the same or my family doesn’t understand me the same. If we could move it back and better understand it, then we could maintain all those additional components of my life.’ So that was really the motivating factor – trying to get people to look at it this presymptomatically, before that diagnosis.”

The decision to start PREDICT occurred in 1998 at an executive meeting of the physician-researcher collective known as the Huntington Study Group, of which Dr. Paulsen was a founding member. PREDICT formally began in 2001.

With its focus on the asymptomatic, PREDICT could help identify and test preventative treatments – the “holy grail” of HD research.

“Eventually, when they have a treatment, we want to intervene as soon as possible, because the sooner we intervene in the brain, the less tissue loss, the less dysfunction, the less toxicity has occurred,” Dr. Paulsen explained. “Even if we slow it 15 percent, which is all that they’ve done in other brain diseases, since HD lasts so many years – we’re thinking 40 years now – 15 percent could be many years where you could maintain a higher level of functioning.”

You can watch the entire interview with Dr. Paulsen in the video below.

Maximizing research

PREDICT seeks to “maximize” HD research, Dr. Paulsen said. “We work with anybody who wants to work on a particular aspect of the disease.”

As the PREDICT flagship, the University of Iowa has collaborated with its sister PREDICT centers and also partners and subcontractors at other academic institutions in the U.S. and abroad. The partners focus on cognitive testing, brain imaging, and motor studies. They include leading universities such as Johns Hopkins University, Brown University, and the Massachusetts Institute of Technology. On protein studies, PREDICT collaborates with Caprion, a private firm.

PREDICT had as many as 33 centers but currently has 27 active sites. Worldwide some 1,500 individuals, including 1,200 gene-positive, have participated in PREDICT. The study seeks to follow 1,000 individuals on a regular basis.

Stimulated largely by PREDICT, Iowa alone has produced a critical mass of innovative HD research in what Dr. Paulsen described as an “explosion” in knowledge about the disease over the past decade.

Among the 20-plus projects at Iowa over the past decade, Dr. Paulsen described research on clinical markers of the disease; biomarkers; proteomics (the study of HD-associated proteins); bone mass and metabolism; MRI scans; PET scans; full genome-wide scans (looking at all the genes in study participants); comparisons of symptoms among people with the same level of genetic mutation; the impact of discrimination and stigmatization on gene-positive people; and the possibility that HD might have vascular, immunological, or inflammatory components.

PREDICT researchers and their collaborators have published numerous scientific articles on presymptomatic HD and other aspects of the disease. These include studies seeking to refine cognitive testing; measure the relationship between estimated disease onset and the likelihood of the use of antidepressants; detect brain cell loss as an early HD imaging biomarker; and gauge the loss of perception and processing time in individuals.

Under Dr. Paulsen’s leadership, Iowa has also taken a key role in the study of juvenile Huntington’s disease, a form of the condition often given little attention by researchers because it accounts for just 10 percent of all HD cases.

Crunching the data

To help form research questions, search for useful biomarkers among the large amounts of data collected by PREDICT-HD, and help plan their use in clinical trials, the project enlists the skills of biostatistician Jeffrey Long, Ph.D., a professor of psychiatry.

“I mainly focus in tracking progression over time,” said Dr. Long, the author of a textbook on the open-source computer program known as R, used widely by statisticians and in the PREDICT research. “We try to make use of every piece of data because we are appreciative of the time you all devoted to the study and want to make sure that we maximize the relevant information for the community.”

Gene Veritas (left) interviewing Dr. Jeffrey Long (photo by Sean Thompson)

The seven-member bio-statistical team led by Dr. Long analyzes the different kinds of data collected individually and in combination. The team also helps draw comparisons between data from gene-positive and gene-negative individuals to account for factors such as cognitive loss due to natural aging.

Additionally, the scientists seek to understand the key relationship between the level of genetic mutation and the age of onset and severity of the disease. They have helped identify one key imaging biomarker: the diminishing size of the brain region known as the putamen before disease onset. They have also noted an abundance of a particular kind of protein in the bloodstream of gene-positive individuals.

A special connection

To coordinate visits by PREDICT participants and administer questionnaires and cognitive testing, the project employs several study coordinators, including research associate Stephen Cross.

“I’ve fallen in love with the population,” said Cross. “They talk about the ‘HD bug.’ I’ve got the bug. There’s something unique about this population. I think it’s the family aspect of it. I would feel like I was abandoning the cause to work with another group.”

With PREDICT since 2008, Cross currently has a caseload of some 80 individuals and their families.

PREDICT-HD study coordinator Stephen Cross (left) conversing with Gene Veritas (photo by Sarah Petitt)

“All of them have their lives changed by the genetic testing, regardless of the results, whether it’s positive or negative,” he observed.

He said that, in the case of gene-positive individuals, especially those from families who can trace the disease back a number of generations, “I think it changes their souls, when you know what’s coming in the family, when it’s in yourself. There’s some kind of interaction in this triad of symptoms – the movement, the psychiatric and the cognitive. I think you’re special because of this disease. I feel a spiritual connection with my participants.”

Brain and body scans

“We have many imaging studies,” said Dr. Paulsen. “We’re looking at the shape changes in the brain.”

Imaging provides a picture of HD without the “need to poke around in the brain,” Dr. Paulsen noted.

 “We already have a very good imaging marker,” she continued. “We can measure the volume of the part that’s particularly sensitive to Huntington’s disease, the striata or the basal ganglia. We can see that it changes a percentage every year of the disease. Even as far back as ten, 15 years prior to diagnosis. But we want to get are even better imaging markers, maybe ones that are earlier or maybe one that gives us a more robust signal. So that’s why we have a lot of projects right now that are really trying to challenge what we can learn from brain imaging.”

Gene Veritas (above) walks through a metal detector in preparation for a PREDICT-HD MRI scan performed after MRI radiology technician Marla Kleingartner (below) secures his head to prevent movement during the scan (photos by Sarah Petitt).

In addition to markers, imaging has revealed new information about the extent of the disease, Dr. Paulsen added. Scientists long thought HD affected only the basal ganglia, the area of the brain responsible for motor function.

“The imaging data that’s been published over the last decade shows that it’s much more widespread in the brain,” she said.

With the lack so far of significant HD biomarkers in the blood and urine, PREDICT is now starting to study CSF collected from a number of its previous and current participants by way of a spinal tap.

(I could not donate CSF because a previous lower back injury made the procedure too risky for me.)

A full-body scan

As a registered nurse, Nancy Downing, Ph.D., takes a holistic approach to HD-affected individuals, always seeking to improve their quality of life.

Several years ago, an NIH seminar on genetics helped solidify Dr. Downing’s interest in HD, she said. Today she seeks to integrate genetics and efforts to improve patients’ quality of life. As a PREDICT researcher, she has especially focused on the effects of diet and exercise and the way in which lifestyle affects the expression of genes.

Just two months ago she helped complete a pioneering twelve-month study in which a group of PREDICT participants underwent dual x-ray absorptiometry, a scan that reveals the composition of a person’s body mass (lean, fat, and bone). This same machine is used to detect osteoporosis.

Nancy Downing, Ph.D., RN, SANE-A (photo courtesy of HDSA Center of Excellence at the University of Iowa)

Dr. Downing hopes to triangulate the data from this study to help understand what HD does to areas of the body other than the brain such as muscle tissue. Evidence already suggests that gene-positive individuals have a shortage of branched-chain amino acids, necessary for muscle building and repair, she said.

Dr. Downing’s work supports the growing notion that HD must be seen as a disease of the body and not just the brain.

Preparing for clinical trials

PREDICT can have an impact on clinical trials and the approach treatments might take, Dr. Paulsen said.

“It’s kind of a when, where, how question,” she said. “I don’t think any of those questions is fully answered, so we have more work to do. But we have answers to those questions that we didn’t have before.

“We didn’t know that there was a when, where, how. We thought that once they get a diagnosis, we’re going to try to treat them with something that we’ve learned from other neurodegenerative diseases. I think in many ways Huntington’s has opened up that box and made it much larger. It’s a very exciting time. And I think it will continue. We’re not even close to the end of the possibilities on where we intervene, (and on) the changes of Huntington’s disease.”

PREDICT, with its unique database of long-term data on presymptomatic individuals, could potentially furnish important data for clinical trials, she added.

“We have this entire cohort,” she explained. “We know exactly how much change they have over time. If we do an intervention, we will be able to determine how much change has occurred. No other study can do that, because if you recruit someone new, you don’t know that individual’s trajectory. We have each individual’s trajectory. We know what type of progression they have. If there was a treatment today, this is the group we should put it in, because we tell exactly what’s going on with that person.”

A potential key treatment

In collaboration with PREDICT and other HD projects at Iowa, the lab of Beverly Davidson, Ph.D., is engaged in research aiming for a clinical trial to test a gene-silencing drug that could at least partially halt HD at its root cause.

This approach would involve the use of RNA interference (RNAi) molecules permanently introduced into the brain via the injection of a virus by a neurosurgeon.

Similar to two separate gene-silencing clinical trials planned by Isis Pharmaceuticals, Inc., and Roche and a team involving Medtronic and the non-profit CHDI Foundation, Inc., the potential Davidson lab therapy aims to reduce the production of harmful huntingtin protein by interrupting the natural translation of the gene into protein.

In HD mouse testing, the lab has demonstrated that RNAi reduces the toxicity of the bad gene in the brain and alleviates symptoms, Dr. Davidson said.

She explained that RNAi is currently under study in a clinical trial for Leber congenital amaurosis, a retinal disorder that leads to blindness in children.

“They put this into the eyes of these children, and the children are showing remarkable, remarkable results,” Dr. Davidson said.

Two of the Leber pioneers, Katherine High, M.D., and Jean Bennet,M.D., Ph.D., are “collaborating with us to develop the gene therapy vectors for Huntington’s disease,” Dr. Davidson noted.

Dr. Davidson said her team hopes to start a clinical trial within the next two years. “That might be aggressive, but we’ve been putting in a lot of effort in the background in the last year or so,” she said.

To learn more about this project watch my interview with Dr. Davidson in the video below.

PREDICT’s ending, gratitude to funders

Although currently operating at full steam, at least in its current form PREDICT is scheduled to end on July 1, 2014.

From 2001-2013, PREDICT received a total of $46.8 million in National Institute of Neurological Disorders and Stroke (NINDS) funding. Additional support has come from the National Human Genome Research Institute and the National Institute of Mental Health. The CHDI Foundation has also infused $15.5 million into the project and is providing further assistance.

In the last five years of the study, PREDICT received $5.6 million annually in federal funds from NINDS. The 2013-2014 fiscal year costs are being covered from funds incurred from previous years.

“I was told that NINDS won’t consider any more budgets over $1 million,” said Dr. Paulsen, noting the high cost of this kind of research. She said Iowa would be unable to continue the PREDICT study in its current form with so little money. Just bringing patients to Iowa is a major expense.

NINDS has experienced cuts in recent years. For fiscal year 2013, the federal government cut five percent of the NINDS budget as part of the $85 billion in overall spending cuts determined by Congress, including the sequestration provisions legislated in 2011.

In addition, CHDI is now shifting its priorities to implementing a new worldwide HD patient study and database known as Enroll-HD.

Nevertheless, Dr. Paulsen recognized the significance of NINDS funding, described by one observer as the largest HD project ever funded by the agency.

“I understand NINDS,” Dr. Paulsen said. “They’ve been cut every year. We’ve been fortunate to receive funding from them for years, and CHDI has supplemented us. They had us expand and train some sites to expand. They have supplemented us when we ran into obstacles. CHDI has been very forthcoming in assisting. So they’re just always there in the wings saying, ‘What can we do to make this go better?’ They really want to push things forward.”

Assessing PREDICT’s impact

Asked to reflect on the ultimate causes of PREDICT’s expected termination, Dr. Paulsen stated that she’s “not sure I have the right answer. I have my opinion. There are centers that have followed research projects for decades.”

The federal government has supported such ongoing centers for AIDS, Alzheimer’s, Parkinson’s, and alcoholism, she noted.

However, once again, HD’s status as a rare disease might be leading officials to treat it as insignificant, Dr. Paulsen indicated. Others might have misunderstood PREDICT to have failed to innovate.

She rebuts those notions.

“The output of this project has been far greater than many other of the ongoing centers,” she observed, adding that HD research has contributed significantly to the study of other conditions. “It’s definitely been a project that has morphed and kept up and pushed the envelope. It would be nice to be funded like other centers that just are kind of automatically rolled over.

“We have to be protective of our resources, but the amount we are learning has just become exponential. It has grown so much and it isn’t stopping. Most of the projects I’m talking about are brand new. They’re just starting to look at CSF, at new imaging markers, at trajectories.”

Despite these setbacks, Dr. Paulsen said that HD research would continue at Iowa. New grant applications are already in the works, she said.

The Iowa HDSA Center of Excellence will also continue its activities.

My future in PREDICT

In line with PREDICT’s goal of tracking patients over time, the Iowa team has already notified me that I should return next year for a follow-up examination, before the July 1, 2014, end date.

Ideally, I should also make a third visit at a later date for the researchers to have sufficient data points. The uncertain budgetary situation has cast doubt on that possibility.

Regardless, I feel privileged to have contributed as an HD-positive individual to the quest for treatments, and I am thankful to the numerous researchers and support staff of PREDICT-HD and the public and for the private funding that has made this initiative possible.

(Next time: advocacy meets science and medicine in Iowa and beyond.) 

Finding America’s passion: the NFL and Huntington’s disease

In a poignant night of football talk and appeals to combat Huntington’s disease, San Diego’s eleventh annual Celebration of Hope Gala put the National Football League (NFL) front and center in the campaign to protect the health of our most important organ: the brain.

NFL Commissioner Roger Goodell headlined the event, titled “NFL: America’s Passion.” Held by the San Diego Chapter of the Huntington’s Disease Society of America (HDSA-San Diego) on November 9, 2011, the gala attracted a record audience of some 600 people at the Manchester Grand Hyatt hotel, including sports celebrities and representatives of major donors such as Qualcomm.

Goodell, interviewed on stage by ESPN football analyst Chris Berman, addressed such controversial topics as recently “testy” player-owner relations and the San Diego Chargers’ quest for a new stadium. Perhaps most of all, Goodell recognized how the NFL must take the lead in making football a safer game for players and, I’d add, especially their brains.

Chris Berman (left) and NFL Commissioner Roger Goodell (photo by Mike Nowak)

“Part of our labor agreement was player health and safety and how we make the game safer,” Goodell explained about the recently signed accord between the owners and the players’ union. “I firmly believe the game is safer and more popular than ever, but I think we can do better…. That’s priority one.”

Goodell cited reducing physical contact during training camp, avoiding the creation of a longer season until the game becomes safer, and prohibiting techniques that lead to frequent injuries.

Goodell’s comments come as concern about brain injuries heightens in the wake of growing evidence about the dangers of concussions not only for the hard-hitting professional players, but the millions of youths who play at all levels.

You can watch the Berman-Goodell interview in the video below.

The football-HD research connection

Although nobody explicitly made a connection between research on brain injuries and HD, both fall into an area of inquiry in which understanding and treating one condition can bring benefits to sufferers of other conditions.

HD research sheds light on Alzheimer’s, Parkinson’s, Lou Gehrig’s, and a host of other brain conditions. Stroke and spinal cord injuries enter the mix, too.

So it’s conceivable that HD research – which has led scientists to plumb the mysteries of the brain – could suggest strategies for preventing and treating brain injuries such as those sustained by athletes.

Even without an explicit mention of an HD-concussion link, the gala drove home the point by bringing together Goodell, HDSA-San Diego, Chargers President Dean Spanos, and other leaders of the football world.

Berman’s lessons from the Johnstons

Prior to his conversation with Goodell, Berman, the gala emcee, underscored the tragedy of HD by recalling his long friendship and professional collaboration with Bill Johnston, the Chargers’ PR director and the husband of Ramona Johnston, who is in the late stages of HD.

“Being a PR director in the NFL is very hard work, but I thought that he was like me,” recounted Berman. “He had a very attractive wife and two very nice children. But I realized that, while that was all true, when Ramona came down with Huntington’s disease, I learned that he and the Johnstons were quite not like me. What I knew was only ten percent, maybe, of what he, Mona, and the children go through each day.”

To hear more of Berman’s remarks, watch the video below.



(You can read more about the Johnstons by clicking here.)

Introducing Ramona

Johnston was the prime mover behind the gala. Ramona was diagnosed with HD in 1999. Unable to care for herself, she has resided the past several years at Edgemoor Hospital, a public facility for people with HD and other debilitating conditions.

“It’s just a horrible, horrible disease,” Johnston explained. “Some have called it the devil of all diseases, because of the symptoms and how it affects people and families. It’s a brain disease that causes brain cells to die.

“And your brain controls obviously everything that you are, mentally, physically. Your brain is who you are, in so many ways. This disease robs you of who you are.”

The Johnstons’ son Jared and another young man then helped Ramona from her wheelchair and onto the stage. They held her in a standing position as Johnston continued his powerful and wrenching testimony.

“If Mona could talk right now, she would just say thank you – thank you for being here – and tell the world about this disease,” Johnston told the audience, his voice filled with emotion. “Tell anyone you can tell. Because you are here to make a difference, and you are making a difference.”

You can watch Johnston and Ramona in the video below.

The Johnstons and HDSA-San Diego

In 1999, I myself tested positive for HD. I vividly remember speaking with Ramona at a benefit walk-run co-sponsored by the Chargers. We commiserated with each other about our gene-positive status.

Ramona was still very lucid, though her symptoms had already started. As I watched her decline over the years as my mother also succumbed to the disease (she died in 2006), I knew that I would follow in their footsteps. Ramona is now 52 – just one year older than I.

Along with Johnston, HDSA-San Diego board members, and numerous volunteers, I have worked assiduously to raise the profile of HD. I attended dozens of board meetings at which Johnston was present. I’ve visited Edgemoor a number of times, several of them with Bill, to gather information and take photos for the HDSA-San Diego website and publications. He and I have exchanged literally thousands of e-mails about all aspects of the HD cause.

In October 2007, I arranged for Bill and Ramona to appear before the oversight committee for California’s multi-billion-dollar state stem-cell initiative to make a plea for HD research funding.

In all, I estimate that in the past decade the San Diego chapter has raised more than $2 million for HDSA.

Sharing the pain

At the gala, I commiserated with another emerging leader of the HD movement, Katie Moser. Katie supports the cause through her position as manager of advocacy and patient support with Lundbeck, the pharmaceutical company that markets Xenazine (tetrabenazine), the first federally approved drug for chorea, the dance-like movements and tremors typical in HD.

“Lundbeck has established a strong relationship with the HD community in the U.S. over the past two and a half years,” Moser told the audience. “I am fortunate to be a part of Lundbeck, because, as some of you might know, I grew up in a family affected by Huntington’s disease, and in 2005 I had the genetic test that shows that I have the genetic mutation that will cause the disease.”

As a sign of hope for the HD community, Moser reported on Lundbeck’s renewed commitment to finding treatments.

Gene Veritas and Katie Moser

I also greeted the Johnstons’ 23-year-old daughter Hayley, a co-chair of the gala and an energetic and highly focused board member who is at risk for HD but has yet to test for the condition. Several years ago her older brother Jared, now 26, tested negative.

Earlier I helped man an HDSA information table, where other volunteers and I solicited people’s e-mail addresses for our chapter database and asked them to sign a petition urging passage of the Huntington’s Disease Parity Act of 2011, a bill in Congress that would make it easier for HD patients to obtain their rightful federal benefits. Terry Leach, a 14-year-old stricken with juvenile Huntington’s disease and confined to a wheelchair, handed out blue HDSA “Care2Cure” wristbands.

At dinner I sat at a table with Hayley’s work colleagues from Qualcomm and also Lindsey Zan, an untested, at-risk woman and one of five people featured in a moving video screened at the gala.

Support from the Chargers

Throughout the Johnston family’s personal ordeal and the San Diego chapter’s collective efforts to raise funds and awareness, the Chargers organization has lent its support in numerous ways, including sponsorships and other donations totaling hundreds of thousands of dollars.

In addition to this year’s gala, Chargers President Dean Spanos and his wife Susie have attended and supported a number of past galas, and Dean’s father and team owner Alex Spanos has also donated to the effort. Dean and Susie’s two sons have also participated in a number of HDSA-San Diego events.

The family is well aware of the fragility of our brains. In 2008, Alex, at 85 and afflicted by severe dementia, wrote a holiday letter to his family lamenting his loss of memory and expressing his love for them. Susie’s father had Alzheimer’s.

In 2003, Dean and Susie Spanos were honored at HDSA’s annual Guthrie Awards Dinner in New York. At the 2008 dinner, Johnston was awarded HDSA’s Marjorie Guthrie Leadership Award. On hand were HDSA-San Diego board members, former New York Governor George Pataki and his wife Libby, the Spanoses, and Goodell.

A cerebral matter for everybody

The San Diego gala hit the mark in describing the NFL as “America’s passion.”

As I have written before, “the Sunday ritual of watching football has taken over as the national religion, a religion where people profess a belief in sports as the path to success in life.” Rooting for our favorite team also permits us to unleash our instinctual tribalism and the primordial exercise of violence.

From left to right, NFL Network analysts Marshall Faulk, Deion Sanders, Michael Irvin, Steve Mariucci, and Rich Eisen close out the gala with football banter and joking with the audience (photo by Mike Nowak).

But the gala transformed that passion from something primeval into a cerebral affair: first, in an intellectual sense, by discussing it a high level, and, secondly, in a literal sense, by recognizing the primacy of the brain.

Playing excellent football requires the utmost stretching of the brain’s powers as the athlete strives for perfect physical coordination and intelligent tactics and strategies.

Promoting brain health requires that we protect, nourish, and exercise our brains. This includes wearing a helmet during football, but it also means redesigning the game, gear, and rules.

Ultimately, I hope, the cerebral passion of the NFL will make brain research a national priority at a time when HD, Alzheimer’s, and other brain disorders are beginning to strain our resources with a massive caregiving burden. Goodell, the NFL teams, and the league hold great sway in our society and have the power to mobilize people in a grand cause.

As an HD-positive person praying each day not to become like my mother, Ramona, and thousands of other Americans who have fallen victim to HD, I fervently hope that the NFL will take the lead of the Chargers, joining the campaign to end HD and protect the brain.

Huntington’s disease in the news and entertainment media – Part I: Stigma and genetic testing

Despite its status as an orphan disease unknown to many, Huntington’s disease occasionally comes into focus in the mainstream news media and the entertainment industry.

HD’s biggest exposure came March 18, 2007, when the Sunday edition of The New York Times featured a long page-one story on 23-year-old Katie Moser, who had tested positive for this devastating, deadly brain disorder and was confronting her fate.

On September 15, 2011, HD entered the discussion again in a Dear Prudence column titled “Deadly Family Secret.” Emily Yoffe, the author of the advice column for the online newsmagazine Slate, responded to a young mother who had just learned that her newborn baby boy was at risk for HD. (Click here to read more.)

The writer, who signed her letter to Prudence “So Devastated,” recounted how, a week after the birth, she learned that her mother-in-law had HD. Thus the young mother’s untested husband has a 50-50 chance of inheriting the disease, and, if he indeed has the abnormal gene, the baby would face the same risk.

That letter once again highlighted how stigma, denial, and ignorance plague the HD community (click here to read more).

Some sound advice

Yoffe provided some excellent commentary and advice, though, as noted below, I found other aspects quite frustrating.

As an HD-positive person, support group member, and 2011 Person of the Year of the Huntington’s Disease Society of America (HDSA), I completely agree with Yoffe that the mother-in-law should have informed her son about his at-risk status, especially given the fact that her own mother had died of HD.

The young mother and her husband are now racing to educate themselves about the disease and its consequences – an anxiety-ridden situation they could have avoided, or at least planned for, had his mother revealed the family history of HD in a timely manner. They could have arranged for PGD, or preimplantation genetic diagnosis, to assure that their baby would be born without HD.

From my own extended family’s experience with HD and my observation of many others in my 13 years as an HD advocate, I believe that full disclosure is always the best policy.

Yoffe recommended that the couple tap into the resources provided by HDSA and its network of support groups and Centers of Excellence for Family Services and Research. She also advised that they consult a genetic counselor to discuss genetic testing for the husband, adding that the wife should inform an at-risk, pregnant cousin about her aunt’s diagnosis. With that knowledge, the cousin can test the fetus for HD.

A deliberate decision

Also, I was deeply relieved to read Yoffe’s advice to the young father that “there is no rush about making that choice” about his own genetic testing.

My own experience with testing supports this approach.

After learning of my mother’s diagnosis the day after Christmas 1995, I wanted to get tested immediately. But after speaking with my mother’s geneticist and becoming involved in the HDSA-San Diego support group, I learned that I should not rush into testing. Testing presented enormous risks involving job security, insurability, and my psychological health. Ultimately, I waited until 1999, when my wife became pregnant, to learn my fate. In 2000 our daughter tested negative for HD in the womb.

The omission of research

However, I disagree with other aspects of Yoffe’s response.

She omitted, or perhaps didn’t know, that a man often passes on a worse form of HD, sometimes causing a gene-positive child to develop juvenile Huntington’s disease. Thus the mother’s failure to inform “So Devastated” and her husband presents potentially even more devastating implications for their new family.

While Yoffe properly described HD as a “particularly cruel” condition, she failed to mention the huge strides made in research to combat the disease. That research provides immense hope for people such as “So Devastated” and her extended family (click here to read more).

A skewed view of testing

As a result of this omission, Yoffe presented a skewed view of genetic testing.

In referencing HDSA guidelines, she wrote that “there is almost never a reason to test a young person for the disease, which tends to strike in middle age.”

Despite the highly appropriate caution about not rushing into testing, genetic testing does play an increasingly important part in the solution to Huntington’s disease. Simply put, scientists, physicians, and drug companies need at-risk, gene-positive, and affected HD people to participate in research studies and clinical trials in order to understand the disease more fully and to test the safety and efficacy of potential drugs. (Click here to read more.)

Testing for HD directly benefits the effort to find treatments to make HD manageable like diabetes or perhaps even to bring about a cure.

By getting tested, at-risk people provide hope – for themselves and for the tens of thousands of people around the world affected by HD.

Treatments ‘on the horizon’

Although many people in the HD community, as well as journalists, still have not perceived this message, it has now existed in the public domain for a number of years.

A prominent example came in September 2005, when Dr. Martha Nance, the director of the HDSA Center of Excellence at the Hennepin County Medical Center in Minneapolis, responded to my own deep fears about HD by demonstrating in a Washington Post article that “treatments for neurodegeneration [brain diseases] are on the horizon.”

Similarly, as I have illustrated with my own experience, at-risk and gene-positive HD people have given testimony regarding the importance of research studies and clinical trials.

Testing no longer just a personal matter

Yoffe’s Dear Prudence column on HD effectively personalized how a “deadly family secret” can devastate successive generations. It reminds us of the urgent need to end the stigma associated with HD (and, by extension, with other neurological diseases).

Rightly so, Yoffe points out the great importance of sharing the truth about a genetic test with other family members and taking advantage of the information and services provided by HDSA.

However, I believe that HD and genetic testing are no longer just personal matters to be interpreted and confronted alone. They involve and impact the entire HD community – including the mutually beneficial, inextricable ties between the researchers and the patients (and potential patients like me and that letter-writer’s husband and son).

To defeat HD, we can never forget the big picture of our quest.

(In Part II, I will reflect on a recent episode about HD and suicide on the TV show Private Practice.)

BDNF and ‘Neurobics’: building a ‘beautiful mind’ against Huntington’s

To avoid the onset of Huntington’s disease, whose killer gene I inherited from my mother, I must do all I can to protect my brain.

In 2001, two years after testing positive for HD, I was inspired by the film A Beautiful Mind to try to think my way to cerebral health. In that film, starring Russell Crowe and Ed Harris (two of my favorite actors), the true-life figure of Nobel Prize-winning mathematician John Nash used his intelligence to distinguish the hallucinations of his schizophrenia from reality and to regain a normal life.

In effect, Nash tricked his symptoms.

I didn’t believe that I could trick HD. Like schizophrenia, HD is a brain disorder, but with far more devastating symptoms – and without a treatment for its root causes. Schizophrenia can be controlled with medication. HD cannot. And, whereas the causes of schizophrenia are thought to be a combination of genetic and environmental factors, HD is completely genetic, with 100 percent of gene-positive individuals eventually becoming symptomatic.

Tricking a gene like that seemed impossible.

Working the brain to exhaustion

But I did believe that keeping an active mind, thinking positively, and working for a cure for HD might allow me to delay onset.

My job as a college professor already provided wonderful stimulation for my brain. I read, wrote, traveled, and lectured regularly. Contact with the young, vibrant students kept me feeling young myself.

As a member of the board of directors of the San Diego chapter of the Huntington’s Disease Society of America (HDSA-San Diego), I took on the hugely stimulating, and time-consuming, task of writing, editing, and producing the organization’s tri-annual newsletter. Using skills gained in my former work as a journalist and my current career as a historian, I delved into the harsh reality of HD as well as the growing body of scientific research towards treatments and a cure.

I ran the newsletter until 2007. During that time, I watched my mother rapidly decline and ultimately die of HD in early 2006, and I rode the emotional roller-coaster of wondering and waiting about the onset of my own symptoms.

I had purposely over-stimulated my brain – many times to the point of exhaustion.

A self-fertilizing garden

In the mid-2000s, I began reading about a new discovery about HD and the brain that provided me with another tool to build my “beautiful mind” against onset: I could increase the amount of a crucial substance for brain health known as BDNF (brain derived neurotrophic factor) by exercising.

A nutrient, BDNF acts like fertilizer for the brain. It is produced in the cortex, the convoluted, outer hemispheres of the brain, and transported into the striatum, the inner, lower level of the brain. Thus, in the words of researchers, our brains function like “a self-fertilizing garden.”

The striatum happens to be the area of the brain most affected in Huntington’s disease. Starting in the early 2000s, scientists working with HD mouse models observed that BDNF levels fell dramatically in the striatum. The lower the amount of BDNF in the mouse brains, the earlier and more severe was their HD onset.

“The promising new findings about BDNF can be exploited even today,” wrote Dr. Marsha Miller on the Huntington’s Disease Lighthouse Family website in 2006 (click here to read more). “There are easy, cheap, reasonably safe ways for people to increase BDNF levels in the brain. Exercise, maintaining a reasonably low weight, and enjoying a stimulating, but not overly stressful, social and mental life all raise BDNF levels. Other BDNF enhancers include the antidepressants known as selective serotonin-reuptake inhibitors (SSRIs), such as sertraline, and a few other drugs.”

This was excellent news for all gene-positive and symptomatic HD people. We could actually increase BDNF in our brains and therefore perhaps delay the onset of the disease or slow down the progression of symptoms!

A hot topic

BDNF was a hot topic at the 2011 Sixth Annual HD Therapeutics Conference from February 7-10, 2011, in Palm Springs, California. In addition to keynoting this meeting, I reported on the scientific presentations. The event was sponsored by the CHDI Foundation, Inc., the so-called “cure Huntington’s disease initiative,” a multi-million-dollar program backed by anonymous donors.

In his presentation on brain receptors that link up with BDNF, Dr. Moses Chao of the New York University School of Medicine observed that research shows that the lack of the substance helps cause the neuropsychiatric symptoms of HD (such as depression).

BDNF, he observed, contributes to a number of important activities in the brain, including the development of the cytoskeleton (the skeleton of the cell) and the ability of the synapses to adjust their strength. BDNF also helps cells survive.

As Dr. Chao pointed out, scientists first thought it might be possible to inject BDNF directly into the brain to help patients. However, in their experiments they encountered difficulties in delivering the BDNF, and it proved to be very “sticky,” meaning that it did not move easily in the brain. There were also negative side effects.

More recently, Dr. Chao explained, scientists have sought ways to bypass these problems. That research has focused on the BDNF receptors, molecules in the brain that link to BDNF so that it can carry out its tasks. Scientists are also examining substances that can bind to the receptors and act as a substitute for BDNF.

There may be other ways to raise the amount of BDNF. Dr. Allan Tobin of CHDI, for instance, has conducted a workshop to investigate the use of molecules that could mimic the effect of exercise on the brain and therefore increase BDNF levels.

For further details on the importance of BDNF and the research efforts towards BDNF-based HD treatments, watch the short video below by Dr. Jody Corey-Bloom of the HDSA Center of Excellence for Family Services and Research at the University of California, San Diego.



For additional background on BDNF, visit the Huntington’s Disease Lighthouse Family. Also see the report on the CHDI meeting at HDBuzz.

For the latest in HD stem-cell research and BDNF, watch the video below by Dr. Jan Nolta, Professor in the Department of Cell Biology and Human Anatomy and Director of the Stem-Cell Program at the University of California, Davis.



Thinking about exercise

To increase my own BDNF, I exercise regularly.

In 2009, when my wife and I decided to build a pool in our back yard, I installed a Fastlane swimming device that creates a powerful current against which I swim. Weather and time permitting, I try to swim 30 minutes three to five times per week.

I try to vary my exercise routine at least a bit. A few years ago, I went through a cycling phase. At times I also have used an elliptical machine for cross-training of the arms and legs.

Now I alternate swimming with 30- to 40-minute walks with my dog Lenny, a three-year-old male cockapoo full of love and energy.

I read once that, in order for exercise to provide maximum benefit for the body, the individual must think about the exercise while he or she is performing it.

So, for example, I don’t listen to music when walking. And I stopped using the elliptical while watching television.

While swimming in recent months, I have imagined BDNF bathing my brain. In my mind, as I stroke against the current, I sometimes chant a mantra: B-D-N-F.

As I wrote in my blog notes the other day, for me BDNF signifies “beautifully derived neurotrophic factor.”

Breaking the routine

After my September 21, 2011, entry titled “Waiting for symptoms: How long can I hang on?”, Dr. Chao wrote me an e-mail encouraging me to work on increasing my BDNF levels “through increased exercise or any other kind of novel activity (travel, learning a new language, etc.).”

I asked Dr. Chao to comment on a recent study that had left me puzzled and worried after I read about it during the summer. Investigators at the National Institutes of Health found that a particular kind of transgenic HD mouse, living in a cage where it could use a running wheel, became symptomatic earlier, had more severe impairments, and suffered greater damage to the striatum because of exercise!

Dr. Moses Chao at the 2011 CHDI HD Therapeutics Conference (photo by Gene Veritas)

“The article on the detrimental effects of exercise was carried out with a transgenic HD animal model that has not been well studied,” Dr. Chao responded. “I suspect it develops some pathology early on that might interfere with exercise. One issue about exercise is it helps if there is novelty. Routine activity (‘running wheels’) can be brain-deadening.”

Dr. Chao’s comments drove home two points: I needed to vary my exercise and personal enrichment and to enjoy them fully. I must not view the avoidance of onset as an obligation or chore, but as life-affirming.

Neurobics: a way to increase BDNF

Dr. Chao followed up by mailing me a copy of a book by the late neuroscientist Lawrence C. Katz, Ph.D., and writer Manning Rubin titled Keep Your Brain Alive: 83 Neurobic Exercises to Help Prevent Memory Loss and Increase Mental Fitness.

“Neurobics” combines the words “neuron” and “aerobics.”

Many people are familiar with the standard recommendations for giving the brain a workout: crossword puzzles, logic puzzles, reading, memory exercises, and engaging with interesting people and “other kinds of challenging activities that exercise brain circuits in different ways,” write Katz and Rubin.

They recommend that people continue with such activities.

But they should also practice the very different kind of exercises involved in Neurobics. These simple mental exercises serve as cross-training for the brain.

“Neurobic exercises use the five senses in novel ways to enhance the brain’s natural drive to form associations between different types of information,” write Katz and Rubin. “Associations (putting a name together with a face, or a smell with a food, for example) are the building blocks of memory and how we learn. Deliberately creating new associative patterns is a central part of the Neurobic program.”

And they add a point of the utmost importance for for HD-positive and HD-affected individuals: it’s well-established that Neurobic exercises increase levels of BDNF!

“In short, with Neurobics you can grow your own brain food – without drugs or diet,” Katz and Rubin state. “The more active brain cells are, the more growth-stimulating molecules they produce and the better they respond.”

Trying the exercises

Katz and Rubin begin with the example of a simple but powerful stimulant to the brain: when you arrive home at the end of the day, rather than relying on your sense of sight, close your eyes and use your senses of touch, hearing, and smell to guide you into the house.

Another exercise, which I tried yesterday, is to brush your teeth with the opposite hand. For a right-handed individual like me, this stimulates the less-used right hemisphere of the brain.

When I walked Lenny the other day, I followed the book’s suggestion of taking a different route. I sensed it was more stimulating for him, too.

Lenny and I leaving on one of our frequent walks

“It’s rather astounding when you think about it,” Katz and Rubin observe. “A certain kind of sensory experience can permanently change the wiring in part of your brain!”

They conclude: “Neurobics uses an approach based on how the brain works, not simply on how to work the brain.”

Everybody in the HD community (and everybody else, for that matter) should read Keep Your Brain Alive. It provides a treasure trove of information about how our brains work and how to protect them from disease and aging.

Quality, not just quantity

When I first learned of HD because of my mother’s diagnosis in 1995, doctors and researchers told me there was virtually nothing an at-risk or gene-positive person could do. HD symptoms are inevitable.

Since then, scientists plumbing the depths of the brain and diseases such as HD have turned up evidence to the contrary.

I wrote in my notes the other day: “YES!!! There are things we can DO to help our brains stave off HD!”

Neurobics may not prevent me from becoming symptomatic, but it very possibly could delay onset and, when it occurs, reduce the devastation of my brain.

From my contact with Dr. Chao, I have learned that I must focus not only on the quantity of exercise, but its quality. I need to stop frantically overstimulating my brain and instead concentrate on exercise, Neurobics, and other activities that will increase my BNDF.

As Katz and Rubin point out, that includes maintaining a rewarding emotional life based on intimate connections to people.

Living neurobically

For my survival, nothing could be more important than exercise, cross-training my brain, and strengthening ties to family and friends.

Although the hope of treatments has increased dramatically, chances are that a treatment will not become available before my symptoms start.

Through HDSA and this blog, I’ve fought for the success of the HD movement. Soon the moment may come when I will need to focus just on me and my own brain, living my final days of mental clarity as neurobically as possible.

Making sense of Huntington’s organizations, and a call for unity

HDSA, HDF, HDDW, CHDI: a mini alphabet soup of Huntington’s disease organizations serves the families afflicted by this devastating brain disease, leaving at least some people confused about each entity’s purpose.

While these organizations often collaborate admirably in their common goal of treatments and a cure, they sometimes conflict, competing for attention and resources and/or disagreeing about the best approach to stopping HD.

Sometimes that conflict occurs within an organization, for example, between the grassroots and the leadership.

These patterns are only human, and they apply even to enterprises striving for the utmost in objectivity, including the doctors and scientists seeking to unravel the mysteries of HD.

My experience

I’ve observed and participated in conflicts ever since I formally joined the HD movement in April 1998. In the San Diego chapter, we tried our best to put the cause ahead of politics. In cases of conflict with the national office, we acted according to what we saw as the best interests of our local HD community.

Lately I’ve read complaints in HD Facebook discussion groups about, in the words of one veteran of the HD movement, an “obvious disconnect between the HD community and the HDSA at a national level as voiced in numerous posts online.”

I aim here not to judge or analyze any particular conflict, but, instead, to provide a brief outline of the specific goals of HDSA – the largest and best-established group – and the other HD organizations.

Gaining perspective

I want to help clear up the confusion of the alphabet soup – and suggest how the apparent "disconnect" might be repaired.

I believe that we act most effectively, and harmoniously, when equipped with accurate information and historical perspective. Providing perspective is part of my job as a professional historian. We cannot plan the future without understanding the past.

I’ve studied carefully and have had contact with all four organizations: as an HDSA chapter board member and 2011 HDSA Person of the Year; as a regular correspondent with one of the HDF board members and a student of its activities; as a participant in an HDDW observational trial and collaborator of the organization’s founder; and as the keynote speaker at the 2011 CHDI research conference.

I recognize the powerful influence of my own perspective on this article: as an HD-positive person whose mom died of the disease in 2006, I desperately await a treatment that will save me from losing my mobility and my mind. I expect conflict and even welcome certain kinds of it; opposing ideas often meld into a better one.

But conflict should not lead us to splinter off into so many different directions that we dissipate our energies and lose momentum towards our ultimate goal. I believe that our community must stay focused on care and ultimately the cure. If not, the HD-affected and HD-positive are doomed.

HDSA

HDSA (the Huntington’s Disease Society of America) was founded in 1967 by Marjorie Guthrie, the widow of folk singer and political activist Woody Guthrie, the most famous American to die of HD.

The very first organization to support HD families, HDSA began as a series of support groups and remains the only organization to offer such help. In the Guthrie tradition, HDSA advocated for HD families and, in the 1970s, helped push Congress to set up a commission to study how to eradicate HD.

After the discovery of the huntingtin gene in 1993 created the possibility of effectively treating HD, HDSA emphasized greater fundraising for scientific research. In 1997 it created the “Coalition for the Cure,” which funded HD research projects to the tune of millions of dollars. Scientists competed for grants based on their qualifications and peer review, that is, a careful examination of their proposals by other scientists. Between December of 2005 and January of 2005, HDSA’s “Generation 2000” program brought in $23 million for the Coalition (click here to read more).

Initially, some in the HD community became angry that HDSA had deemphasized its primary mission of supporting care for HD patients and their families. Partly in response to this, starting in the late 1990s HDSA created Centers of Excellence for Family Services and Research, which gave greater visibility and some additional funding to local HD clinics around the country, practically all of them associated with universities.

With the founding of the CHDI Foundation, Inc., in 2003 (see below), HDSA’s role in research diminished substantially. Although it continues to fund some important research, it focuses largely on chapter development, education, family services, fundraising, and advocacy.

HDSA, headquartered in New York City, has a number of development field officers and assistants in various regions of the country. But the organization’s lifeblood is the thousands of individuals active in some 40 chapters and affiliates and 21 Centers of Excellence: affected family members, support group members, volunteers, physicians, nurses, social workers, and others.

In late June, a record total – more than 1,000 people – took part in the 26th annual HDSA convention in Minneapolis, an indication of the organization’s grassroots strength.

At the same time, however, some in the community have criticized the national office in what they see as its inability, or unwillingness, to back local projects or provide assistance to financially strapped families.

Some have also questioned why such a small portion of the HDSA budget goes to research – just seven percent (about $370,000), according to the 2009-2010 annual report. That is a far cry from the early 2000s. Research is the smallest part of the budget, with 26 percent going to family services, 20 percent to fundraising, 20 percent to chapter development, 17 percent to education, and ten percent to “management and general.”

As illustrated below, the CHDI Foundation now provides more research dollars in one year than HDSA did in a decade.

In an interview with me in May, HDSA CEO Louise Vetter acknowledged that the organization’s national board recognizes the need for local assistance but, with a current annual budget of only $8.5 million, lacks the wherewithal to help more than it currently does (click here to read more). She added that HDSA is striving to increase the budget to as much as $20 million. A bigger budget would allow HDSA to increase support for both research and local projects.

Louise Vetter (photo by Gene Veritas)

Despite these frictions, HDSA remains the “go-to” organization for HD families.

In conjunction with the Centers of Excellence, HDSA is the only organization that provides the large array of services essential to the HD community: clinical care, genetic counseling, genetic testing (with an established protocol), support groups, educational and other chapter events, chapter fundraisers, public and legislative advocacy, caregiver assistance, medical publications (including the important Physician’s Guide to the Management of Huntington’s Disease), and the administration of highly crucial clinical trials and observational studies.

(No HD organization provides nursing home care or any published guide on how to find a good facility. Families often must choose a facility for their loved ones on their own.)

HDF

Founded by psychoanalyst Milton Wexler, the HDF (Hereditary Disease Foundation) began in 1968 as the Los Angeles chapter of HDSA. In 1974, Wexler broke off from HDSA to formally start the HDF.

The HDF arose out of the very first major conflict in the HD movement. Wexler, the husband of an HD-affected woman and father of two at-risk daughters, started his own foundation because he believed private research funding, and not just the government support sought by Marjorie Guthrie, should play a part in the quest to find treatments. His and Marjorie’s strong personalities also clashed.

HDF established offices at the Wexler family base in Los Angeles and also in New York. As a scientific foundation, it had no chapters, support groups, or clinics. It had one goal: to promote research towards treatments and a cure. Towards that end, Milton Wexler held seminars with some of the leading scientists of the late twentieth century.

Like the HDSA, the HDF issues grants on a competitive basis. Its single focus allowed it to put a high level of funding in research. In 1990, for example, it spent almost $600,000 on research – nearly double the amount of HDSA.

The HDF spearheaded the search for the all-important gene that indicates HD. Wexler’s daughter Nancy, a Ph.D. in clinical psychology, spent years collecting thousands of blood samples from the world’s largest HD extended family in Venezuela.

This research led to the discovery, in 1983, of a genetic marker for the HD gene, thus permitting the development of indirect genetic tests indicating a person’s probability of carrying the defective huntingtin gene. In 1993 the actual location of the gene was discovered, leading to a 100-percent accurate genetic test. (Click here to read more about Nancy Wexler.)

To a large degree, Nancy Wexler and the HDF’s work laid the basis for a revolution in HD research over the past two decades. In the 1990s and early 2000s, HDF began efforts to discover specific treatments.

Nancy Wexler (left), the late Milton Wexler, and Alice Wexler (photo by Mariana Cook)

Toward that end, in 1997 the HDF foundation received a “substantial anonymous gift” to set up an internal program known as “The Cure Huntington’s Disease Initiative” (CHDI). (This first CHDI should not be confused with the current CHDI Foundation.) According to the HDF summer 2002 newsletter, “the CHDI approaches HD as a problem in practical drug discovery.” It supported research projects for “studying potential new drugs, developing screening methods for quickly assessing the effectiveness of new drugs, and studying the mechanism of disease and potential drug targets” (click here to read more).

In 2003, with CHDI picking up steam, the HDF put more than $20 million into research (click here to read more).

But, like HDSA, the HDF has seen better times in terms of its finances. According to the winter 2010 HDF newsletter, the foundation last year awarded $800,000 in grants and contracts (click here to read more) – less, in real terms, than its 1990 amount. Again, the presence of the CHDI Foundation, discussed below, partly explains this decline.

Despite their initial differences and later frictions, HDSA and HDF maintained a reasonable working relationship.

Today HDF remains on the cutting edge of HD research, attracting great attention from the scientific world at its biennial meetings.

Nancy’s older sister Alice chronicled the early story of the HDF and her family’s struggle against the disease in the acclaimed 1995 book Mapping Fate, from which I have drawn some of the information for this vignette of the HDF. In 2008, she published another important book, The Woman Who Walked into the Sea: Huntington’s and the Making of a Genetic Disease, which helps to explain why HD carries such a terrible stigma.

Everybody in the HD movement should read Alice Wexler's books.

HDDW

HDDW (Huntington’s Disease Drug Works) started in 2003 under the leadership of Dr. LaVonne Goodman, a physician to HD families and the president of the HDSA Northwest chapter, and her husband Dr. Nathan Goodman, one of the participants in the historic Genome Project. HDDW is based in Seattle. It has no chapters, support groups, or family services.

While HDSA and HDF sought a long-term solution to HD, the Goodmans instituted a “treatment now” program using safe supplements and medications approved by the federal Food and Drug Administration for other conditions and shown to be effective in HD mice.

For several years, Dr. Goodman monitored a small group of HD patients, but without conclusive results.

Dr. LaVonne Goodman (photo by Gene Veritas)

I have taken the supplements for about six years and, although there is no scientific proof that they have helped me, I remain free of the classic symptoms of HD (click here to read more about my strategies for avoiding HD).

Because Dr. Goodman questioned the conventional wisdom of HDSA and many scientists and doctors, she stirred controversy. She even had to resign as a chapter president.

Several years later, however, Dr. Goodman resumed her collaboration with HDSA and has been a featured speaker at the national convention. She chairs the Northwest chapter’s efforts in family services and education. She has also collaborated with CHDI and the Huntington’s Study Group (HSG), an international coalition of physicians and researchers conducting HD research.

The mother of two at-risk children from a previous marriage, Dr. Goodman today attends to several dozen HD patients in the Northwest.

She now focuses on preparing the community for clinical trials, absolutely essential for testing potential drugs for safety and efficacy. On July 30, she co-organized the Inaugural Clinical Research Symposium in Seattle with support from the Northwest chapter and the pharmaceutical firm Lundbeck.

Dr. Goodman is also working to establish HD “standard of care guidelines” to supplement HDSA’s Physician’s Guide by taking into account care strategies utilized by HD experts around the world. According to Dr. Goodman, the new guidelines “can improve the quality of care delivered by busy doctors who have limited HD experience and need time-efficient guides” (click here to read more).

CHDI

The CHDI Foundation, Inc., grew out of the HDF’s CHDI program. It is backed by the same anonymous donors.

In the HD community, the CHDI Foundation is probably the least known of the organizations, despite its enormous impact since arriving on the scene in 2003.

Like the HDF, the CHDI Foundation focuses on one goal: finding treatments and a cure for HD. It has offices in three cities, but no support groups, chapters, or family services. The foundation’s goals are implemented by CHDI Management, Inc., presided over by Robi Blumenstein, an attorney who built a successful career in merchant banking.

In addition to the HDF, the anonymous donors had previously provided support to the HDSA. In each of the past several years the CHDI Foundation has donated $1.2 million to HDSA.

The donors, however, wanted to try a different research approach from those of HDSA and the HDF and decided to start a new organization.

With the establishment of the foundation and its management firm, the acronym “CHDI” no longer had any official meaning, although in this blog I have continually referred to its original meaning, the “cure Huntington’s disease initiative.”

In the simplest of terms, CHDI Management is a virtual biotech company. I have visited all three of its offices: the administrative headquarters in Manhattan (which also has two researchers) and the research offices in Princeton, NJ, and Los Angeles. CHDI Management has no labs – not even a microscope.

Its impressive staff of “drug hunters” – many of them recruited from the highly competitive pharmaceutical industry – conceive, fund, and manage specific research projects carried out in labs at pharmaceutical companies and universities. In all, CHDI Management scientists work with more than 600 researchers.

CHDI Management scientists travel frequently to consult with the scientists implementing the projects. For several years, I have tracked one of these projects at Isis Pharmaceuticals, Inc., in nearby Carlsbad, CA. With a revolutionary approach, Isis and CHDI Management aim to attack HD at its genetic cause. (Click here to read more.)

At the Princeton office, the scientists are helping design effective clinical trials and ways to measure the effectiveness of the proposed drugs.

Like HDSA and HDF, CHDI Management holds regular conferences. Although some might disagree, I described the CHDI Management meeting as the “Super Bowl” of HD research because of its international reach and intense focus on practical steps towards a victory in the fight against HD.

Scientists at the 2011 CHDI Foundation's research conference (photo by Gene Veritas)

CHDI Management’s annual budget varies according to the needs of the researchers and the projects. In the current year, it plans to spend approximately $100 million. In the fight against HD, it is the largest private initiative ever.

CHDI Management raised HD’s profile in the world of science and put drug discovery into overdrive. Pharmaceutical giants such as Pfizer began to pay greater attention to HD. Whereas no specific treatment strategy existed after the discovery of the gene in 1993, the HD research community has now identified an astounding 700-plus potential targets (ideas for drugs) to attack HD. Much of that progress has resulted from CHDI Management’s massive commitment.

Crucially, CHDI Management has the resources to transform the most promising of those targets into actual drugs and help guide them into clinical trials.

A potentially positive division of labor

About a year ago a scientist starting work on an HD project hinted to me that the lack of a single disease organization might hamper efforts to discover and implement treatments. Why, he seemed to ask, couldn’t our community get its act together?

I understood his point. Drug companies likely would find it easier to deal with one organization. It would also create a perception of unity, as opposed to one of squabbling.

But there is also a positive side to having multiple organizations: the competition of ideas and strategies. Thanks to the current schema, the organizations are less likely to become complacent in their search for treatments and a cure. Unlike the volunteers in the field, disease organization employees earn a living from that quest, and they are more likely to feel passion for their work in an environment of freely flowing ideas, constructive criticism, and healthy competition.

The unique history and focus of each organization also benefit the HD community by creating a sort of division of labor. CHDI and HDF (and also the HSG) do the heavy lifting on research, while HDSA raises awareness and provides the grassroots infrastructure for patient care and clinical trials. HDDW plays a constructively critical, supportive role in the entire process.

Also, sometimes the institutions overlap one another, especially when it comes to research. Many of the scientists receive funding from two or more organizations and attend their respective conferences. What counts most for scientists is not the origin of their funding, but the fact that the money allows them to conduct the research necessary for finding treatments and a cure.

A call for unity

As someone who began my journey with HD at an HDSA support group and worked many years in the trenches as an anonymous volunteer, I sympathize with those at the grassroots who express frustration about HDSA and/or about the other organizations.

However, as someone who has held important leadership positions in my profession, I also understand the challenges of administration.

I believe strongly that several things must happen in the HD community.

With leadership comes great responsibility. The leaders of the HD organizations should always be open to dialogue with the grassroots. They should display a willingness to learn from and even adopt the innovations of the grassroots.

People at the grassroots have a great responsibility, too. They should remember that these organizations must respond to needs expressed from around the country and even from overseas, as CHDI expands the scope of its efforts in the quest for treatments and a cure. Grassroots activists need to resist the very human temptation to adopt an “us versus them” attitude with respect to the leadership, while, however, also maintaining a constructively critical approach and making their voices heard.

Collaboration, negotiation, debate, dialogue, and the search for common points of interest are hard, but I believe that in the end they can bring us more quickly to a victory against HD.

But dialogue needs to be informed.

The members of the HD community should continually strive to learn about the disease organizations. At the same time, each one of us needs to constantly evaluate his or her part in the fight against HD.

In the end, from the presidents to the family stressed out by HD to the volunteers, we all need to remember: Together we can beat this disease!

(Note: This article was originally posted on October 3, 2011, and updated on October 4, 2011, to correct several factual errors.)

Memories of the DNA car

We all measure life by milestones: the first steps, graduating from high school, the big raise, sending a child off to college.

For many Americans, cars symbolize important stages in life, from practicing in one for the driver’s license test to buying that first shiny new one to driving the family on summer vacations.

We spend so much time in cars that they seem like members of the family.

For me, gene-positive for Huntington’s disease, my 1999 Corolla CE took on a very special meaning. Like a quiet but supportive partner, it literally carried me through many crucial moments.

Buying an Altima

With a deep tinge of nostalgia, I parted with my Corolla on January 7. In 2009, thanks to President Barack Obama’s efforts to get the economy moving, my wife and I refinanced our mortgage and included in the package a new swimming pool, aka the “Obama stimulus pool." As 2010 came to a close, my wife urged me to take advantage of the auto companies’ big sales, designed to put some pep into that sluggish industry.

I hesitated, but the moment seemed too good to pass up. So, on December 30, the day before my 51st birthday and just four days before the big sales expired, we took the plunge and bought a 2011 Nissan Altima 2.5 S. We got a great deal on the car and the loan.

I felt great driving the car home, especially because the Altima checked in as the top-rated family sedan in the Consumer Reports car ratings.

The Corolla, my first new car

After the holidays, I got to work on getting the Corolla ready for sale.

My 1999 Corolla CE

Important memories flooded into my mind, beginning with the night my wife and I bought the car on a Friday night in fall 1998.

The Corolla was my very first new car, which we financed with an auto loan.

Prior to that, I had a long history with used vehicles.

Used cars, family, and HD

My very first car was a 1970 Volkswagen Beetle that I bought in high school for $500. In 1982, I received a 1977 Oldsmobile Cutlass S as a gift from my maternal grandparents after graduating from Yale.

My grandfather and I had spent many an hour driving around the Cleveland area in the several Cutlasses that he owned. I couldn’t have imagined a better graduation gift.

Eight years after my grandfather died of heart failure at age 79, my mother received her diagnosis of Huntington’s disease.

I could only conclude that Gramps had carried the genetic defect at a low level of impact and, in one of the strange twists when the male is the HD carrier, passed it on to my mother in a more pronounced form, dooming her to more than 15 years of symptoms and ultimately death at age 68 in 2006. My grandmother, who died at age 87, also of heart failure, remained sharp until almost the very end. She never displayed any HD symptoms.

In 1991 I bought my next car, a 1987 Dodge Shadow, from my father. Soon thereafter he became the “HD warrior” who cared for my mother until she had to enter a nursing home in mid-2005. The Shadow was the car my wife and I shared at the time of Mom’s diagnosis in 1995.

A painful scrape

I’m not at all superstitious, but the Corolla came with an almost prophetic message attached. Its California license plate was “4DNA921.” DNA was playing a bigger and bigger role in my life as my mother deteriorated and I worried about my own at-risk status.

Not long after the purchase, in June 1999, I decided to get tested for HD. We needed to know my status to plan for avoiding the disease in the child that we had just conceived.

As I have described in other blog entries (click here to read more), the news of my positive result left me disoriented.

As I attempted to maneuver the still new-looking Corolla out of the space in the office building’s parking garage, I turned the wheel too sharply. The car pulled too far to the right, causing the right front fender to scrape against a column.

I was able to rub out most of the mark. Nobody ever noticed, in fact. But I knew exactly where the scratches were. For many years, just looking at the car brought painful memories of that fateful moment and the feelings of confusion and anger that followed.

License tag 4DNA921

By then, “4DNA921” had taken on an entirely new meaning. The car constantly reminded me that I was HD-positive.

But the tag was also like a badge that I displayed to other members of the HD cause as I became ever more active in the San Diego chapter of the Huntington’s Disease Society of America (HDSA-San Diego). The Corolla was my DNA-powered, anti-HD car.

“Wow, now that’s an interesting license plate,” an HD caregiver remarked to me one time.

Our first pregnancy ended in a miscarriage, but in October 1999 we conceived again. In January 2000, we received the news that our daughter-to-be had tested negative in the womb for HD. That was one of the happiest moments of our lives – to be matched only by the day in June 2000 when we drove our “miracle baby” home from the hospital in the faithful Corolla.

Over the next decade I took the Corolla on countless assignments for HDSA-San Diego. I drove to board meetings at the San Diego Chargers headquarters, where board member Bill Johnston, the team’s PR director, arranged for us to meet. The Corolla seemed puny and insignificant next to the top-of-the-line Mercedes Benzes and other super-luxurious cars in the Chargers’ parking lot. But I didn’t mind. I had the DNA on my side.

I drove the Corolla to Celebration of Hope Galas, HD support group meetings, interviews with members of the HD community, and meetings of the California state stem-cell agency’s oversight committee. The Corolla transported thousands of copies of the HDSA-San Diego newsletter, which I edited and published from 2001 to 2007.

Last February I drove the Corolla to the Parker Palm Springs hotel for the fifth annual international research conference of the CHDI Foundation, Inc., informally known as the “cure Huntington’s disease initiative.” At such a tony resort the Corolla once again seemed out of place, but it steadfastly carried me to my destination and back.

Balancing frugality and safety

For the longest time, I vowed to myself to keep the Corolla – and the DNA plates that came with it – until researchers found a cure for Huntington’s.

At the time of the sale, it had only 83,000 miles. I wanted to avoid sinking $25,000 into the new Altima because, like so many HD families, we need to budget conservatively. I will inevitably develop HD symptoms, and that will mean a dramatic loss in income and long-term financial security for my family. I also very much liked the fact that the Corolla got 29 miles per gallon in the city and 40 mpg on extended trips.

But my wife pointed out that the Corolla was starting to have problems. Indeed, although the engine could last much longer – I have a friend who drives a 1978 Corolla! – last year I had to spend several hundred dollars on a new visor and repair work on the starter.

My wife also frequently reminds me of the way an SUV blind-sided the Corolla in May 2009, sending me to the hospital and causing more than $3,000 in damage to the vehicle. Since then, she has become ever more worried that another accident could seriously harm or even kill me or our daughter, whom I drive to school and other activities practically every day. Recently, she started saying she would forbid me to take our daughter in the Corolla!

The 1999 Corolla has just a driver’s and passenger air bag, whereas the new Altima has six, along with many other features that make it safer. The Altima is also a much bigger car.

No matter how serious a financial crisis HD might bring for our family, I could not risk our safety on the road.

Opting for some comfort

On the more optimistic side, my wife convinced me that it was time to move up from the Corolla and treat myself with some comfort and enjoyment while driving.

The Corolla is a starter car, she pointed out. At age 51 and with perhaps not much time left before symptoms start, I deserved to drive something better.

At the dealership we could have gotten the base model Altima for $5,000 less than we spent.

“The $5,000 we’d save could go into our daughter’s education fund,” I told my wife.

But, after thinking about how my wife and I would have to manually adjust the driver’s seat with a clumsy system, I opted for the more comfortable S model. I also added such conveniences as a power seat and Bluetooth cell phone system.

The S model includes a leather steering wheel with radio controls accessible to the fingertips. This last feature is especially important, because my daughter constantly asks me to switch stations while I’m driving.

Compared to other cars in the market, the Altima is far from luxurious. But it’s definitely a big step up from the Corolla.

A new car, a new era in HD research

I’ll receive the plates for this car in the next month or two.

I’m wondering: what letters will I get this time?

The Corolla symbolized frugality, worry about HD, and my intense activism for the cause.

What will the Altima symbolize in 2011 and beyond?

In part, I purchased the car because just before Christmas I received a clean bill of health from my doctor at the local HD clinic. Because my mother most likely became symptomatic in her late forties, every moment that I live free of symptoms is a bonus (click here to read more).

When we bought the Corolla in 1998, only five years had passed since scientists had discovered the HD gene. Relatively little hope existed for my generation of gene-positive individuals.

In contrast, in late 2010 we could feel far more optimistic as scientists sought ways to turn some of the 700-plus potential treatment targets into actual medicines.

There has never been a more exciting time for HD research. Although there is no guarantee of treatments or a cure, for the first time our community can feel some confidence that help is on the way.

The upcoming drive to Palm Springs

My own confidence has grown in the last few years as I have observed CHDI pursue such revolutionary projects as its collaboration with Isis Pharmaceuticals, Inc., to stop HD at its genetic roots.

As I’ve written recently, I will deliver the keynote address at the next CHDI conference in Palm Springs on February 7.

With the Altima, I’ll drive to Palm Springs much more comfortably and confidently.

Let’s all hope that this new confidence will bring a major research breakthrough in 2011.