‘Darkness replaced by hope and light’: taking stock of Huntington’s disease research

As the Huntington’s disease community in 2015 enters a promising phase of clinical trials for remedies that might slow or halt the progression of the disease, one of the world’s leading HD scientists recently took stock of the significant progress made over the past several decades.

“The horizons for therapy were very far away,” Michael Hayden, M.D., Ph.D., the President of Global Research and Development and Chief Scientific Officer of Israel-based Teva Pharmaceuticals, said during a February 10, 2015, presentation about his company’s latest efforts to defeat HD.

Dr. Hayden recalled how, 40 years ago, HD was virtually unknown in his native South Africa and many other countries. HD-afflicted people faced stigma and were left to cope with their disease “in isolation and despair,” Dr. Hayden remembered of his first contact with the disease as a young medical student.

“It was just a dream then that there would be pharmaceutical companies interested in Huntington disease,” he said. (In some countries HD is referred to as “Huntington,” not “Huntington’s.”)

However, as Teva and other companies work towards HD treatments, the outlook has changed dramatically.

“We are now in a place of really tremendous hope,” Dr. Hayden declared enthusiastically. “The darkness is replaced by hope and light. At the end of the tunnel we are seeing this light now, not only with this [Teva’s] drug but other trials you are hearing about.”

Dr. Michael Hayden (photo by Gene Veritas)

Reexamining a promising drug candidate

Dr. Hayden offered these remarks during a Huntington’s Disease Society of America (HDSA) research webinar titled “Pride-HD: a dose finding, safety and efficacy study of pridopidine in HD patients.” (Click here to watch the webinar.)

Pridopidine was first tested in two clinical trials – in Europe and North America – by the Danish pharmaceutical company Neurosearch. The company, although it observed some interesting effects, did not achieve sufficiently positive results to bring the drug to market.

That’s because the chosen “endpoint” in the study, the way of measuring the drug’s effects, didn’t show a result significant enough for obtaining regulatory approval, Dr. Hayden explained. Neurosearch chose only a subset of motor symptoms as the study endpoint.

But some researchers still believed pridopidine had potential as an HD drug. Dr. Hayden and Teva studied the overall impact of pridopidine and, after obtaining the license for the drug from Neurosearch, have decided to run an additional clinical trial, called Pride-HD (Pridopidine Dose Escalation in HD). Teva is using a different endpoint, the so-called total motor score, a measurement of all the motor symptoms.

Dr. Hayden observed that patients in the earlier pridopidine studies actually showed improvement in motor symptoms caused by HD such as chorea, or involuntary movements. Pridopidine also improved eye movement substantially, he said. It also stabilized levels of dopamine, a neurotransmitter and hormone involved in movement control, mood, and motivation.

Patients’ depression, another telltale HD symptom, also did not worsen, Dr. Hayden noted.

Aiming for broader impact

“There may be some broader affect on other features of Huntington disease,” he added. Additional studies of pridopidine in animals have indicated that it brings about changes in the brain, might be “neuroprotective,” and might help with improving thinking and feeling, he explained.

Therefore, Teva will add other key endpoints to the Pride-HD study: cognition, mood, and quality of life. The study also will assess the effect of dosages of pridopidine higher than those given patients in the earlier trials.

Pridopidine “could theoretically have some effect to change the course of the illness,” Dr. Hayden observed. “And wouldn’t that be exciting?”

Pride-HD enrolled its first patient in April 2014 and will continue throughout 2015. Teva aims to enroll 400 patients at 54 sites in North America, Europe, and Australia. If the results are favorable, Teva could seek regulatory approval for the drug in late 2016, Dr. Hayden said.

As HD specialist Dr. LaVonne Goodman noted in her February 18 commentary on the potential of pridopidine, “recruitment is not going well for Pride-HD.[...] The bottom line is that finding new drugs for HD takes a lot of work, good trials and a long-term commitment from HD families and investigators. If we don't join this or other trials, we will never have new drugs for HD: not for ourselves or the next generation."

To learn more about Pride-HD and how to participate, refer to the above-mentioned link to the webinar or call HDSA at 800-345-4372.

Teva is also conducting a clinical trial of the drug laquinomod for use in HD, Dr. Hayden noted. Laquinomod is thought to reduce the inflammation of the brain in neurological disorders. Click here to learn more about the trial.

Another historic moment

As a carrier of the HD gene mutation, I listened to Dr. Hayden’s comments on the long-term progress of HD research with great hope.

Scientists have observed that managing HD effectively likely will require a cocktail of drugs. Pridopidine is yet another potential element in the mix. (I have reported on many of the elements in this blog over the past ten years. Click here and here to see recent examples.)

Having tracked the HD movement for nearly 20 years, I also appreciated Dr. Hayden’s important reminder that the quest for effective treatments is a lengthy process. Science and clinical trials require time and investments of money and intellect.

I wrote this article in Palm Springs, CA, just before the start of yet another historic mark in the HD movement: the 10^th Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc., at the Parker Palm Springs hotel February 23-26. In the past I have referred to this event as the "Super Bowl" of HD research.

In Palm Springs, I will listen to other scientists take stock of the search for HD treatments.

I also expect to witness yet further examples of researchers replacing the darkness of Huntington’s disease with hope and light.

For yet more perspective, watch my interview with Dr. Hayden at the 2011 HD Therapeutics Conference in the video below.

Gene Veritas interviews Huntington's disease expert Michael Hayden from Gene Veritas on Vimeo.

Huntington’s disease patients ‘feel better’ after taking Auspex compound to control chorea in clinical trial

Huntington’s disease patients in a recently concluded clinical trial for a potential new drug to control the disease’s characteristic involuntary movements reported that they “felt better” overall.

The trial showed that the compound reduced chorea substantially and with fewer and milder side effects than a predecessor drug, a significant step, although it does not address the cognitive and psychiatric symptoms of HD nor attempts to be a “cure.”

Auspex Pharmaceuticals, a San Diego biotech firm focusing on hyperkinetic movement disorders and other rare diseases, announced the highly favorable results for the Phase III clinical trial for its substance SD-809 on December 16, 2014.

Like Xenazine, the first ever drug approved by the federal Food and Drug Administration (FDA) for Huntington’s, SD-809 attacks chorea, the involuntary, sometimes dance-like movements caused by HD’s devastation of the brain.

As one of its “endpoints” (research targets), Auspex used the Patients’ Global Impression of Change scale to measure whether patients actually felt better. The patients’ responses showed convincingly that they did, in part as a result of controlling chorea.

“I don’t think that there’s ever been a therapy with patients with HD that has actually demonstrated that patients actually feel better on this type of patient assessment,” Pratik Shah, Ph.D., the Auspex president and CEO, said in an interview at Auspex headquarters on December 23.

“This is something that in the past not everyone has been able to appreciate: the impact of chorea on the life of a patient. We wanted to put in an instrument that really asked the question: ‘Does this matter to the patient? Do you feel better?’ Given the fact that perhaps not everyone outside the HD community really understands the adverse impact of chorea on the life of a patient and their family, this was an important question to assess.”

The trial doctors were asked a similar set of questions about the trial participants. “The clinicians as well saw a favorable result here,” Dr. Shah said.

As a carrier of the HD gene mutation who lost his mother to HD nine years ago this month, I was thrilled to hear the news about SD-809 and to visit Auspex for the second time in recent months. You can watch my reaction in the video below.

Reducing chorea and side effects

Significantly, the clinical trial demonstrated that SD-809 reduced chorea substantially.

“We saw a 37 percentage-point improvement in the SD-809 arm and 16-percent improvement in the placebo arm, so it’s 21 percentage points above placebo,” Dr. Shah said. “This is very robust, when you look at all the historical data [from the Xenazine trial].”

Dr. Shah pointed out that the data are the sum of all the observations made on and by the participants.

“One person can have a two- or three-point reduction and experience great benefit, while a different individual may have the need for a greater numerical reduction,” he said.

According to one analyst who compared the two compounds, the reduction in chorea is about the same seen in the Xenazine trial.

However, SD-809 had fewer and far milder side effects than Xenazine. Both are taken as a pill. Neither attacks the root causes of HD, nor the psychiatric and cognitive symptoms that devastate most HD patients. So such drugs are not a “cure.”

Referring to the study data, cited in a press release on the Auspex website, Dr. Shah affirmed that SD-809 caused low levels of side effects such as depression, restlessness, anxiety, insomnia, sleepiness, irritability, and fatigue. SD-809 caused no problems with swallowing in any of the patients –  2.2% of those trial participants on placebo did experience difficulty with swallowing.

The minimal level of those side effects is important in HD, because the disease itself often causes such symptoms, in particular depression, which appeared to be lower in the SD-809 arm compared to placebo, Dr. Shah noted.

Pratik Shah, Ph.D. (photo by Gene Veritas)

In an assessment of the total motor (movement) score of the standard HD disease rating scale, SD-809 led to improvement – an outcome lacking in the Xenazine trial, Dr. Shah pointed out.

The improvement in this score suggests that movement problems other than chorea could be improving, he added.

Yet another trial measurement showed that participants’ “physical functioning” improved with SD-809, that is, movement required to do daily tasks such as walking and climbing stairs.

SD-809 as seen by HD experts

Ninety individuals took part in the Phase III trial, called First-HD, at 34 sites across the U.S. and Canada. Half received SD-809, half a placebo. All participants had at least moderate chorea. The study was double-blinded: neither doctors nor participants knew who was receiving the drug. This is the most rigorous form of clinical trial. Auspex ran the trial in conjunction with the Huntington Study Group (HSG).

None of the First-HD participants was taking Xenazine at the time of the trial. Auspex and the HSG also conducted a trial known as ARC-HD to study another group of participants already taking Xenazine but who switched the next day to SD-809 for the trial. ARC-HD demonstrated that the switch between drugs did not affect the reduction in chorea and occurred with no serious side effects. In fact, patients shifting to SD-809 had somewhat less chorea, and at smaller dosages, Dr. Shah noted.

“New, safe and tolerable therapies for chorea treatment are clearly needed to make this disease an increasingly treatable condition,” said Samuel A. Frank, M.D., an HSG researcher and principal investigator for First-HD, in the Auspex press release. “The primary and secondary efficacy results from this study were confirmed by the Huntington Study Group independent analysis. These clear and unequivocal results are clinically meaningful and suggest that SD-809 may play an important role in the treatment of Huntington's disease symptoms.”

Dr. LaVonne Goodman, the founder of the Huntington’s Disease Drug Works program and a clinician who has attended to scores of HD patients, echoed the optimistic conclusions about SD-809’s efficacy.

“This drug treats chorea with many fewer side effects associated with tetrabenazine [Xenazine],” she wrote. “And most important it improved quality of life.[…] If this drug lives up to the press release, it could/should replace antipsychotic drugs as primary treatment of chorea in Huntington's disease.”

Although not yet convinced that SD-809 is better than Xenazine overall, the researcher-written website HDBuzz.net affirmed in a generally positive article that the “very well-run” Auspex trials “prove that SD-809 could be a useful new tool to help fight excessive movements in Huntington’s disease.”

How it works

Xenazine’s scientific name is tetrabenazine, a drug discovered in the 1950s. HD-affected individuals used tetrabenazine for decades in Europe and Canada, where U.S. families purchased the drug on an individual basis in person or through mail order. Only in 2008 did it receive FDA approval.

Chemically SD-809 is an improvement on Xenazine. It is deutetrabenazine: a molecule with atoms of deuterium (heavy hydrogen) attached.

“We used in select places deuterium as a building block,” Dr. Shah explained, pointing to a model of SD-809 made by an Auspex scientist.

Dr. Shah explains the structure of SD-809 using a model built by an Auspex scientist. The colors represent the compound’s five atoms: carbon (black), hydrogen (white), oxygen (red), nitrogen (blue), and deuterium (green). In scientific terms, SD-809 (deutetrabenazine) is a VMAT2 inhibitor. (photo by Gene Veritas)

Very much like Xenazine, SD-809 inhibits certain chemical actions in the brain in order to avoid such symptoms as excess dopamine, which can lead to the involuntary movements of HD, Dr. Shah explained.

He added that the addition of deuterium “enabled this molecule to be broken down in the body more slowly and so it sticks around longer.” As a result, the levels of the drug in the bloodstream become “smoother.”

For patients, this means smaller, less frequent dosages and potentially a more optimal performance of the drug, he said.

Applying to the FDA

After the conclusion of First-HD and ARC-HD, over 90 percent of the trial participants (excluding a few who dropped out) entered a follow-up study so that Auspex can further analyze the effectiveness of SD-809 and the compound’s side effects. This ongoing study gives participants access to the compound, including those who were receiving the placebo during the trial.

On January 12, Auspex released additional good news resulting from its ongoing analysis of SD-809: whereas Xenazine’s instructions warn about the possibility of an abnormal, prolonged heartbeat, SD-809 does not cause such a symptom to the point of medical concern.

Dr. Shah stated that Auspex hopes to complete a New Drug Application for HD and SD-809 during the first half of this year. Review of such applications typically takes from six to twelve months, depending on the circumstances.

“We have a huge sense of urgency, especially given these [clinical trial] results, to do everything we can to put the application together as soon as we possibly can,” Dr. Shah emphasized.

Auspex has also submitted for FDA approval a list of possibilities for SD-809’s eventual commercial name.

On January 14, Auspex received orphan drug designation from the FDA for use of SD-809 in Tourette syndrome, another rare movement disorder. The company is currently conducting a Tourette clinical trial.

Last year, Auspex received the same designation for HD. Orphan drug status – for conditions affecting fewer than 200,000 people in the U.S. – provides special incentives for companies to produce drugs for these maladies.

Awaiting a price and revenues

Dr. Shah said that the company has not yet researched the price of the drug.

The exorbitant cost of some orphan drugs has caused deep concern among affected families and patient advocates. Lundbeck, which markets Xenazine, has a program to assist HD families with the high cost of its drug, which can reach $50,000 at the wholesale level for an annual supply (click here to read my previous article on the cost of orphan drugs).

“We remain committed as a company to making SD-809 available to those who need it as much as we can,” Dr. Shah commented.

As a young company that only sold stock publicly for the first time in 2014, Auspex has yet to generate revenues. Investors continue to support the company as it moves forward with clinical trials and new research, Dr. Shah explained.

Xenazine will lose its market exclusivity in August 2015 and become subject to generic competition. This development could put additional pressure on Auspex to market its drug affordably, but, at the same time, furnish the opportunity to stress its compound’s greater safety.

New hope and a platform for future research

“We haven’t had a positive study in HD in many, many years, so it’s really an opportunity to celebrate a success that we’ve seen here and to recognize that this is an important step forward for the field and to kind of spread some good cheer and to have renewed hope for the field,” Dr. Shah concluded about the SD-809 trial. “It is also important for the community to remind the people who don’t know treating chorea does matter. It can affect and does affect people’s quality of life.”

Auspex hopes to use the SD-809 project as a platform for researching possible treatments that attack the causes of HD, Dr. Shah said.

“We’re always on the lookout for what makes sense to invest in there,” he added.

The success of the drug and its acceptance by HD families and clinicians could help provide the revenues needed to fund the new research into better remedies, he said.

Dr. Shah (left) with Gene Veritas (photo by Rachel Kenny, Auspex)

Fighting – and writing – to stay healthy: ten years of 'At Risk for Huntington’s Disease'

Ten years ago today, I launched this blog to explore the depths of living at risk for Huntington’s disease and to unburden myself of the fear of its inevitable symptoms.

Frankly, I did not expect to still be writing at 55.

At that age, my mother had developed chorea (the involuntary movements associated with HD) and was experiencing serious emotional and cognitive symptoms that would soon prevent her from speaking and caring for herself. This year marks the sad 20^th anniversary of her official diagnosis. She died of HD in February 2006 at the age of 68.

I tested positive for the HD genetic mutation in 1999.

I strongly believe that my work on this blog – research, reflection, writing, advocacy, and networking – has helped me delay my own HD onset.

I cannot scientifically prove this, but evidence strongly suggests that mental stimuli and other forms of enrichment can positively affect the course of this disease and other neurodegenerative conditions.

Researchers have told me privately that they believe my mental activity has helped keep me stable. “Keep doing what you’re doing,” they say.

Gene Veritas with his tenth anniversary blog posting (photo by Gene Veritas)

Launching the blog

Life can be an emotional roller coaster. HD families ride the tallest and most twisted one, with HD gene carriers like me facing a terrifying descent into symptoms.

Starting in 2001, I wrote and edited Conquest, the tri-annual newsletter of the San Diego Chapter of the Huntington’s Disease Society of America. However, while revealing the stories of many HD-affected individuals and their families in Conquest, I never wrote about my own family’s plight.

I started At Risk at the urging of Norman Oder, a fellow Yale University graduate and colleague at the Yale Daily News.

As a young journalist in the 1980s, Norman by chance wrote an article about a New York area HD family. After we reconnected years later, he edited some of my Conquest articles. Coincidentally one told the story of that same family, part of which had moved to California.

In the early 2000s Norman and I brainstormed about how to increase media coverage of HD, including my own story, as a way to strengthen the cause and attract potential donors.

With that goal in mind, I initiated the blog to address the many complex issues faced by presymptomatic mutation carriers like me as well as untested at-risk individuals.

I didn’t realize at the time how much it would help me sort out my thoughts, engage with others in the HD community, and nudge HD activism. In February 2011, I examined this blog as an advocacy tool during my keynote of the Sixth Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc. In June 2011 I was named HDSA’s Person of the Year, an honor I never could have achieved without this forum. “I know, too, that this award is not just for me,” I wrote, “but for everybody affected by HD: the at-risk, the gene-positive, the symptomatic, the families, and the unsung heroes of America, the caregivers.”

From the start, Norman has applied his editing skills to virtually every article, almost always sending back revisions within a few hours. He has also suggested a number of topics and pushed me toward rigor when it’s tempting to just hope.

Norman is my “HD alter ego,” and a great friend.

(Later in 2005, Norman began his own long-running blog, a daily account of Brooklyn’s most controversial real-estate project, now called Atlantic Yards/Pacific Park Report.)

A stalwart supporter of my activism, my wife Regina has reflected with me on the content of numerous articles. Our daughter Bianca has witnessed me writing and posting articles. Now a teenager, she has a record she can consult of her grandmother’s demise and her father’s writing and coping strategies.

Explicitly and implicitly, Regina and Bianca permeate the pages of this blog. More than anything else, their presence and love motivate me to fight HD and to improve as a husband, father, and human being.

Gene Veritas (left, aka Kenneth Serbin), Norman Oder, and Regina Serbin (photo by Bianca Serbin)

Bringing hope

In that first year (2005), I wrote 17 articles. However, over the next three years I could only write 18 articles. I was distraught over the death of my mother from HD. I even acted out HD symptoms.

During those first four years, I focused primarily on my family’s struggles to care for my mother and how living with the gene affected my feelings and life.

With the help of my psychotherapist and a more effective set of medications for depression and anxiety, I started to turn the corner in late 2007.

In late 2007 I also wrote my first blog article about the potential of stem cell research for finding HD treatments. Along with other southern California advocates, I set up the very first presentations about Huntington’s disease before the state’s stem cell agency.

From that point on, the hope for treatments buoyed me emotionally and became a frequent theme of At Risk for Huntington’s Disease.

Expanding the research updates that I wrote for Conquest, I started doing on-the-scene reporting and in-depth interviews with researchers. In April 2008, I visited Isis Pharmaceuticals, Inc., in nearby Carlsbad, CA, to produce an article on the company’s ambitious efforts to stop HD very close to its genetic roots.

This year Isis will conduct the long-awaited Phase I clinical trial to test its potential gene-silencing drug.

Broad coverage

The blog expanded to cover many of the difficult issues impinging on the HD community, including abortion; advocacy for a congressional bill to update the government’s disability criteria for HD;  the difficult discussions young at-risk people face during dating; and the challenges of finding adequate nursing home care for HD patients.

“I really absolutely admire your bravery in exposing this disease in a realistic and unapologetic way,” wrote Stella, another HD blogger, in a comment on one of my articles. Such comments help keep me going.

Writing the blog helped me think through the process of going public about my HD status after nearly 15 years of advocating anonymously and seven years of blogging under the pseudonym “Gene Veritas,” which I maintain as a symbol of our community’s fight for the cure.

Now, as I meld my HD advocacy with the career of Kenneth P. Serbin the professional historian, I have come to view the blog as a primary historical document of the “new and harrowing human experience of living in the gray zone between a genetic test result and onset of a disease.”

An emotional vent

Above all, the blog is an emotional vent.

With you, my readers, I can share my feelings about facing a terrible, currently untreatable disease, build forces to defeat the profound stigma surrounding HD, and bolster advocacy to improve care and seek the cure.

Through At Risk for Huntington’s Disease – and the HD community I have reached on Facebook – I have gained many new brothers and sisters determined to survive HD and passionate about the noble aim of bettering humanity by solving a major medical and scientific puzzle.

Often, producing articles for the blog envelops me for hours and sometimes days as I research, travel, photograph, shoot video, write, revise, and post, and then engage with readers via e-mail and social media.

Sometimes I go to bed too late – not good for someone at risk for a disease that disturbs the body’s natural rhythms.

As I prepare to post an article, I experience a torrent of emotion, followed by a deep sense of relief.

The memories of twenty years of dealing with HD come flooding back, but in the end I have hope.

Awaiting effective treatments

This article is posting number 197 in At Risk for Huntington’s Disease.

I am grateful that very soon I will be able to post number 200.

Tonight I will raise a glass to the blog.

I know it’s still a long shot because of the inevitability of HD symptoms, but I want to remain healthy long enough to write the article celebrating the discovery of a treatment so effective that I can stop worrying about HD and retire the blog.

Police killing of man with Huntington’s disease spotlights need for affected families to emphasize proactive, dignified approach

The shooting death of a Philadelphia-area man apparently suffering from Huntington’s disease, which perhaps led him to try to run over police officers with his car, has once again raised the perilously common issue of how police misunderstand HD.

Beyond prompting anger and the need for better police preparation, the death of Joseph A. Pacini can also stir the HD community to combat the stigma of the disease, redouble efforts towards treatments, and emphasize the dignity of affected individuals.

According to reports in the Philadelphia Inquirer (click here and here), Pacini, 52, died Dec. 30, 2014, in a town near Philadelphia after officers from three departments fired at least 22 shots, wounding him in the head, neck, shoulders, and chest.

Pacini’s one-time girlfriend and a close friend told reporters that he suffered from HD. Family members said that Pacini’s father, who had HD, committed suicide when Pacini was 21.

For the second time in less than four months, the incident raised the issue of police response to HD-afflicted individuals. In September, police in the small town of Westover, WV, held down Jeffrey Bane for nearly ten minutes after he clashed with officers; he struggled to breathe and pleaded for help. A bystander captured the scene on video (click here to read more).

Investigators in the Pacini case are conducting tests to confirm his HD status and whether he was using drugs and/or alcohol. The local district attorney is also investigating the justifiability of the shooting.

(Sadly, most media reports missed the HD angle. One, in the New York Daily News, reinforced the ignorance and stigma surrounding neurologically and mentally impaired individuals by poking fun at Pacini and referring to him in tabloid parlance as a “sicko.”)

Joseph A. Pacini (from his Facebook page)

A volatile situation

According to the Inquirer, Pacini led a troubled life, failing to finish his college studies, posting conspiratorial and threatening YouTube videos, and fighting with his mother, the police, and others.

“[HD] is very often confused with schizophrenia, especially with those who do have the mental disorder predominant in the beginning," Louise Vetter, CEO of the Huntington's Disease Society of America (HDSA), told the Inquirer. She said that HD can involve "paranoia, anxiety, really, really strong fixation on things.”

“HD does not fit well into the norms of society,” advocate Jonathan Monkmeyer, a Philadelphia-area resident whose wife Sheryl died of HD in 2009 at 46, said in a Facebook conversation with me. Jonathan did not know Pacini, but as Sheryl’s full-time caregiver for many years he understood the awkward and difficult social situations HD people face.

“This describes another tragic end to a difficult life for a person thought to have HD,” Martha Nance, M.D., the director of the HDSA Center of Excellence at Hennepin County Medical Center in Minneapolis, MN, and the author of the preface to HDSA’s Law Enforcement Training Guide, wrote in an e-mail after reading press coverage of the incident.

“It is easy to focus on the police departments’ actions that directly led to Mr. Pacini’s death, and shout for a different approach, criticize the police for ‘not knowing he had HD,’” she added. “But I’m not sure that the presence or absence of HD would necessitate a difference in the officers’ approach to a volatile situation.”

In the Pacini case, mental illness independent of HD seemed to play a role, Dr. Nance observed. She pointed to the “general issue of access to mental health care” as a key factor in such situations.

“In medicine, we believe that the police need to be involved if there are homicidal threats, and we, too, call the police if we feel that we are unsafe or in danger as we see a patient in the clinic or the hospital,” Dr. Nance emphasized.

‘Be more public about HD’

“The other issue, and more relevant to the HD community, is WHAT CAN WE DO to keep our Joseph Pacinis from getting to these kinds of crisis points,” Dr. Nance continued. “And I think the first thing is to be more public about our disease.  HD families, more than anyone else, treat their disease as a terrible secret, a stigma, something to hide and be ashamed of. This creates a mindset that passes through the generations, that HD is like being in a terrible underground tunnel filled only with darkness, and the only way out is suicide, or to emerge with explosiveness and anger.”

By avoiding genetic testing and contact with doctors, HD people “delude themselves into thinking that they are not entering the dark tunnel,” she wrote.

The community needs to stop viewing HD “with hopelessness and despair,” she added.

“What makes a difference is what you do BEFORE you die,” she wrote. “I can tell any number of amazing stories of amazing people with HD and their families who have done amazing things for themselves, each other, the HD community, and the world at large.  There IS life after a diagnosis of HD, but it can’t emerge if you are stuck in the dark tunnel.”

Everybody in HD families can and should to get involved, Dr. Nance observed.

“If you are scared, find a support group, or talk to your parent, sister, cousin, friend, pastor, teacher, or perhaps even your doctor,” she wrote. “If you have a family member who is unconnected, floating out there, undiagnosed, struggling, reach out to them. Bring them to an HD meeting, or have them come with you to YOUR appointment.”

Enroll-HD: proactive participation

I was numbed by the news of Joseph Pacini’s death.

After I had explored the Jeffrey Bane incident and then noted in my most recent article that HD activists had skillfully reacted by building HD awareness at an international police officers’ conference just weeks later, the Pacini incident seemed surreal.

Emotionally, I cast about for a way to react. I concluded that I could do nothing in the case of someone who had already died.

Then, reflecting on Dr. Nance’s encouraging words, I focused on how I could best contribute to the cause: I went for my January 5 appointment to register in Enroll-HD, a worldwide registry and observational study of HD patients, HD gene carriers like me, untested at-risk individuals, family members, and volunteers.

Enroll-HD aims to facilitate scientific understanding of HD, identify potential participants in all-crucial clinical trials, and therefore speed the process of finding treatments. Enroll-HD is sponsored by the CHDI Foundation, Inc., the non-profit virtual biotech focused solely on developing HD therapies.

I recalled what Joe Giuliano, CHDI’s director of clinical operations and the chief Enroll-HD administrator, told me last year: the larger the pool of potential clinical trial participants, the faster trials can take place.

At the HDSA Center of Excellence for Family Services and Research at the University of California, San Diego, I provided a research assistant with information on my health and HD status, answered several health- and HD-related questionnaires, performed a battery of cognitive tests, underwent a neurological exam, and gave three vials of blood, which will be used to confirm my gene-positive status and provide evidence in the search for HD biomarkers (signs of the disease that can be used to test the efficacy of potential drugs).

I also participated in several HD research studies sponsored by the Center of Excellence.

A nurse (above) prepares to draw blood from Gene Veritas for the Enroll-HD study (photo by Ajay Nathan, HDSA Center of Excellence research assistant). Below, Gene Veritas and Ajay Nathan discuss Gene's participation in Enroll-HD (photo by Andrew Herndon, HDSA Center of Excellence).

Striving for a life lived well

During the four hours of testing, I worried that I might someday lose control as Joseph Pacini did.

My thoughts were troubled: what if I act aggressively towards my wife and daughter?

I found strength in Dr. Nance’s concluding observation about the HD-affected and gene carriers:

“A life lived WELL with HD can resonate into future generations just as easily as a difficult life or a terrible death.”

As long as I can, I will strive to defeat HD by assisting in the search for treatments and by spreading awareness and understanding.