At key FDA meeting, Huntington's disease community insists on faster search for treatments

The Huntington’s disease community sent a powerful message to the U.S. Food and Drug Administration (FDA) at the September 22 meeting on HD patient-focused drug development: the agency must do its utmost to facilitate clinical trials and speed the search for effective treatments.

“We discovered the gene – we don’t have a cure,” declared Nancy Wexler, Ph.D., the famed researcher who initiated the search for the huntingtin gene while watching her mother suffer and ultimately die from HD. She addressed the panel of ten FDA officials and audience of some 200 HD family members and advocates at the agency’s headquarters in Silver Spring, MD. “We did that [discovery] in 1993.”

Along with Wexler, two panels of HD family members selected by the FDA to make presentations about the disease and current lack of effective remedies, as well as other participants in the unusually large meeting, described HD’s cruel devastation and the exhausting burden for caregivers.

The Huntington’s Disease Society of America (HDSA), which advocated for the meeting under the new requirements for patient feedback established by Congress for the FDA, sought to provide the FDA with a more tangible and comprehensive view of HD’s reality, all too familiar to affected families.

The FDA doesn’t conduct drug research, but its regulators must approve all clinical trials and new drugs in the U.S.

The plethora of symptoms

Many presenters and audience commenters emphasized the plethora of cognitive, behavioral, and other symptoms involved in HD in addition to chorea, the involuntary movements traditionally but erroneously labeled the key diagnostic signifier of the disease.

“I have all of the symptoms that have nothing to do with chorea,” stated presenter Julie Rosling, 72, of Orange, CA. Forced to retire some ten years ago from her pharmacist job, Julie participated on the five-person panel about the daily impact of HD.

I first met Julie almost 20 years ago in San Diego at the local HD support group, several years before I tested positive for the genetic defect that causes the disease. At most meetings the group had three breakouts: for the affected, caregivers, and untested individuals and asymptomatic gene carriers. Julie and I participated in this last breakout group. Sharing our most intimate fears about HD, we became friends.

I hadn’t seen Julie in a few years. I had long admired her intelligence, profound knowledge of HD science, and healthy lifestyle. My wife and I viewed Julie as a model for avoiding HD and, once her symptoms started, for living with the disease. She has late-onset HD, in contrast with most patients, who experience onset between 35 and 55.

From left to right, Frances Saldaña, Julie Rosling, Reed Rosling, and Gene Veritas (aka Kenneth P. Serbin) (photo courtesy of Frances)

‘I can’t play Chopin anymore’

At the FDA meeting, I was shocked and saddened to see how the disease had, as Julie put it in her presentation, greatly affected her demeanor.

“There are so many different types of symptoms,” Julie said, adding that HD must no longer be seen as just a brain disease. She described how she can no longer drive, suffers from insomnia and gastrointestinal difficulties, and fears choking, a common problem with HD.

“I fall all the time when I go up and down the stairs,” she continued. “The thing that’s the most important […] is that my symptoms are affecting every system in my body.”

Sadly, HD has robbed Julie of many favorite activities. Each December, Julie, a painter, sent out exquisitely designed holiday cards. Several years ago, she wrote in her holiday card that she could no longer paint the cover for her cards.

Those beautiful cards always brought me a glow of hope. I have missed them.

“I can’t play Chopin on the piano anymore,” Julie said at the FDA. “I can’t walk to the corner and back.”

HD has hampered her social interaction, too, because of her slurred speech.

“My symptoms have never gotten better,” Julie concluded. “They get worse every single day. I am a living example of what this disease is all about.”

Once again, I had looked into the genetic mirror and viewed my own highly probable future decline.

You can watch Julie’s presentation in the video below. To watch other presentations, click here to visit my video album of the meeting.

'I Can't Play Chopin on the Piano Anymore' from Gene Veritas on Vimeo.

FDA ‘blown away’ by turnout

“I think it was a very successful day,” said HDSA CEO Louise Vetter in an interview with me shortly after the meeting. “I’m really pleased with how full the room was, not only from the patient and community side, but also the FDA. They had a full docket of folks who wanted to be in the meeting to listen to the HD community.[…] There were more FDA staff in the room than is typical for a public hearing.”

The FDA’s level of interest demonstrated its “commitment to paving the way for new therapies for HD,” Vetter added. The FDA was “impressed” with the “urgency” and “commitment” of the HD community.

“The FDA was blown away,” she said, adding that the agency at the last minute had to set up a room “three times larger than what they planned.”

FDA regulators at the Public Meeting on HD Patient-Focused Drug Development (photo by Gene Veritas)

Several dozen HD community members participated in the hearing via webcast. In addition, representatives attended from CHDI Foundation, Inc., the nonprofit virtual biotech focused exclusively on the search for HD therapies, and the pharmaceutical industry.

The HD hearing took place in the morning, followed by a Parkinson’s disease meeting in the afternoon. The FDA had initially combined HD and Parkinson’s concerns into a single event, but HDSA convinced the agency to divide the meeting because of significant differences in the two conditions and the different treatment approaches, Vetter explained.

“We had more people than Parkinson’s had planned, and given the difference in prevalence, the FDA really took notice,” she said.

“I’m just so pleased with how many caregivers and family members really came prepared to succinctly share their stories and open up about the impact of the disease and their hopes and wishes. I know that the FDA heard that.”

FDA regulators Leonard Kapcala, M.D. (above) and Peter Como, Ph.D., and Lei Xu, M.D., Ph.D. (below) watch presentations by HD advocates (photos by Gene Veritas)

Still time to submit comments

HDSA requested the hearing as soon as the Congressional mandate for patient-focused feedback to the FDA went into effect in 2012. HDSA told the FDA that it could learn much from HD as a genetic disease, given a clearly identified gene and a community of affected families with a serious need for treatments, including preventative remedies for presymptomatic gene carriers, Vetter noted. HDSA also said HD could be a case study for understanding and treating other diseases.

In addition, HDSA will submit to the FDA survey responses from 3,600 HD-affected individuals and family members regarding the impact of symptoms and desired treatments, Vetter noted in her public comments at the hearing.

The public can provide further feedback to the FDA until November 23, 2015, by clicking here.

Several months after the public comment period closes, the FDA will complete a “Voice of the Patient” report on HD, Vetter told me. HDSA will carefully review the report and provide feedback.

You can watch Vetter make her public comments in the video below.

HDSA CEO tells FDA: Study the Broad Feedback from from Gene Veritas on Vimeo.

Advocating for the presymptomatic

During my brief remarks (audience members got only two minutes per commentary), I told of my mother’s demise, our daughter’s gene-negative status after testing in the womb, and my luck at remaining presymptomatic at 55, well beyond the point where my mother experienced many symptoms.

“I would like to see a medication that prevents me from ever getting any kind of symptoms,” I said. “There’s got to be a really open dialogue with the scientists on the new areas such as gene-silencing.”

I referred to the disappointment among HD advocates that the first gene-silencing clinical trial for HD, by the Carlsbad, CA-based Isis Pharmaceuticals, Inc., is happening outside the United States. (Phase I of the trial started in July in Europe and Canada; click here to read more.) I remarked that some drug company executives think the FDA too inflexible regarding new approaches. I urged the regulators to consider the new biomarkers (signs of disease and drug efficacy) scientists are seeking to measure in the blood, cerebrospinal fluid, and brain measured with new techniques.

Many presymptomatic people don’t get tested “because of the immense fear of the disease and the fact that there are no treatments,” I added during the final round of comments. “There’s also associated with genetic testing and getting your results a lot of suicidal tendencies.”

I recalled my suicidal fantasies from the early years of my family’s struggle with HD, when I saw my mother declining. Those ended after the birth of my daughter, I added.

“The presymptomatic population out there really needs to be part of the conversation,” I urged.

The urgent need for treatments

The FDA regulators, unsurprisingly, offered little comment on the proceedings; they wanted to listen and learn.

After returning home, on September 25 I requested an interview to follow up on the above-mentioned points, and more, including calls from families with juvenile HD patients for JHD-specific approaches to clinical trials and treatments. I have not yet received a response, but will write an update when I learn more.

However, HDSA CEO Vetter recalled for me the nub of her conversation with William Dunn, M.D., a neurologist and the FDA’s director of the Division of Neurology Products, immediately after the meeting. Dr. Dunn had welcomed the participants at the meeting’s start.

“He’s very committed to this,” Vetter said, referring to the search for HD treatments. “He was very impressed, very grateful for the input of the families, and very committed to making sure that, as therapies move forward to FDA consideration, they will be efficient in their review, that the FDA’s not sitting on anything. The last thing they want to do is be accused of keeping something meaningful out of the hands of families. They’re very committed to being very expeditious and thorough.”

Along with many fellow HD family members, I believe that the FDA gained a clearer understanding of our community’s suffering and the urgent need for treatments.

* * *

For the FDA’s recording of the meeting, click here. Be sure to visit my video album for other perspectives expressed at the hearing. For additional photos from the meeting, click here.

For the perspective of Parkinson’s specialist Jeanne Loring, Ph.D., click here.

(Note: HDSA paid for my travel to Silver Spring and a night of lodging. The views expressed in this article are wholly mine.)

HD advocate Katie Moser (left), HDSA CEO Louise Vetter, and advocate Emma Burris (photo by Gene Veritas)

The Huntington's disease high-wire act

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

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

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

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

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

Tough decisions

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

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

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

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

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

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

Passion vs. obsession

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

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

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

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

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

A radio interview

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

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

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

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

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

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

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

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

‘HD doesn’t have me’

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

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

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

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

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

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

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

The diary of a Huntington's disease activist

In my previous blog post, I described my secret, second career as a Huntington’s disease activist.

Today I was off from work because of the Easter holiday, so I decided to catch up on a few of the most pressing tasks on my HD “to do” list.

Recently I’ve received questions from other members of the HD community about how to engage in or improve upon work in the cause. I hope that this blog article – which I am fashioning as a kind of diary entry – will provide some suggestions.

Also, next month is HD Awareness Month – an opportunity for everybody in our community to reflect on our roles in the cause. On May 7, I’ll be speaking on the topic of effective activism at the annual convention of the Northern California Chapter of the Huntington’s Disease Society of America (HDSA).

6-7 a.m.

After having gone to bed early (9:30 p.m.), I arose to prepare scrambled eggs for our “miracle baby,” who tested negative in the womb in January of 2000. She’s taking state achievement tests this week, and my wife and I want her to eat an extra good breakfast to help boost her performance. As my wife got her ready, I checked the first e-mails of the day from the HD Facebook discussion groups to which I belong, and did my morning stretch.

8 a.m.

I returned home after dropping my daughter off at school. With both my wife and daughter off to their activities and the house quiet, I performed my morning deep breathing exercises and mini-meditation.

This morning ritual helps me face yet another day of living at risk for HD while juggling job, family, and other responsibilities.

8:10-9:15 a.m.

I started thinking about tonight’s monthly HD support group meeting. I always come back from support group distraught at seeing people with HD and hearing others tell their sad and difficult stories of living at risk or experiencing the initial symptoms such as problems with driving.

I don’t want to go – but I must. I decided to go back to bed for some extra sleep – and to help my mind work through the fear so that I can function normally the rest of the day.

9:20-10:30 a.m.

I awoke after about an hour of sleep feeling less depressed.

I responded to some work and personal e-mails, and then turned to HD e-mail again. I exchanged several messages with the local special events coordinator for HDSA-San Diego about corporate sponsorship logos for our chapter website, which I oversee. These logos need updating to reflect new 2011 supporters of the cause here in San Diego.

I also made a few phone calls about Senate Bill 648, the Huntington’s Disease Parity Act of 2011. If passed, the law would make it easier for HD-affected individuals to obtain federal benefits.

I found out over the weekend that the sister of a very good friend is a staffer to Rep. Xavier Becerra (D-Los Angeles), a member of the powerful Committee on Ways and Means and the ranking member of the Ways and Means Subcommittee on Social Security. Rep. Becerra did not back the bill last year, when advocates obtained 153 co-sponsors in the House of Representatives. His support is crucial, and we need to get him on board. (Click here for a previous blog article on the bill.)

I recalled HD advocate Allan Rappoport’s sage advice: if you don’t know a representative or senator, ask five friends for help. At least one of them is bound to know an elected official or how to contact one.

10:30-10:45 a.m.

I phoned Jeri, a middle-aged woman who cares for her nephew Tony, who was stricken with HD in his early 20s. I want to write a blog article about care, using Jeri’s selfless dedication to Tony as an example. Completely disabled, Tony now lives at Edgemoor Hospital, a public facility where Jeri visits him each evening to help him eat dinner.

Jeri told me that Edgemoor was in the news because a 50-year-old non-HD patient, who was recovering from a car accident, allegedly bled to death because of hospital neglect (click here to read news coverage).

Later I sent the link about the article to the HDSA-San Diego board and support group facilitators.

Edgemoor personnel have cared for dozens of HD patients over the years, and I fear that I, too, may end up there if my family cannot care for me or afford to find proper assistance. I have visited Edgemoor on several occasions. The facility seems to have improved, but the news of neglect – and a $2 million legal payment from the County of San Diego to the dead man’s family – left me deeply worried about the fate of HD people there.

11 a.m.-noon

I drafted the letter below to Sen. Barbara Boxer (D-CA) about the HD Parity Act.

Dear Senator Boxer:

I urge you to join Senator Kirsten Gillibrand as a co-sponsor of S. 648, the Huntington’s Disease Parity Act of 2011.

One of the cruelest of conditions, Huntington’s disease destroyed my mother’s brain, leaving her unable to walk, talk, or swallow. HD is like a combination of Alzheimer’s and Parkinson’s, with psychiatric problems added to the mix. After more than 15 years battling the disease, my mother died in 2006 at the age of only 68.

I tested positive for HD in 1999. There is no treatment or cure, and I will very likely develop symptoms within a few years. I am 51.

This genetic killer strikes people like me in their prime, saddling our families with a huge caregiving burden and ruining their finances.

Individuals affected by HD qualify for Social Security Disability benefits and Medicare. However, bureaucracy and inaccurate information about the disease make it difficult for HD people to actually secure their benefits. Some are even denied those benefits.

S. 648 would enact two very important changes in the law.

First, it would require the Social Security Administration to update its decades-old, inaccurate disability criteria for HD.

Second, it would waive the two-year waiting period for patients to receive Medicare benefits, thus bringing assistance quicker to families in dire straits.

Passage of the HD Parity Act will bring immediate relief to HD-affected families. I have paid Social Security taxes all of my working life, and my wife and daughter will urgently need federal benefits when I can no longer help support them. Passage of the Act will provide at least some peace of mind for us as we fight as a family to deal with the devastating symptoms of Huntington’s disease.

12:20-1 p.m.

I started writing this entry.

1-1:30 p.m.

I ate lunch (tilapia, brown rice, roasted vegetables, olives, and yogurt) and took my midday dosage of my Huntington’s Disease Drug Works supplements (trehalose, Omega-3 fish oil pills, and Coenzyme Q-10).

1:30-1:55 p.m.

I normally take a “power nap” this time of day, but because I slept extra in the morning and need to work on this post, I skipped it in order to write.

1:55 p.m.

I got ready to pick up my daughter from school. I normally spend part of Monday afternoon at home with her as she reads or does homework, and at around 4 p.m. I drive her to her weekly piano lesson. Today we moved her lesson up to 3:15 so that I can prepare for tonight’s support group meeting. I usually leave around 5:30.

3:45

I read an e-mail noting the “lukewarm response” of California Senators Boxer and Dianne Feinstein to the HD Parity Act. We will have to redouble our efforts to get them behind the bill.

6-7:30 p.m.

I attended the support group meeting. Tonight the HDSA-San Diego board made its annual visit to the group to discuss chapter activities and the goal of national HDSA to strengthen ties to the grass roots, providing greater service for HD families. I was happy about the renewed commitment to care.

I also conversed with several HD people. Once again, I looked into the “genetic mirror” – my own probable future as a gene-positive individual.

Big goals – but little ones, too

As you can see, there’s no secret ingredient or spectacular formula for being a Huntington’s disease activist. Such work requires time, focus, and clear objectives.

It also requires a strong belief in the cause. Without commitment, it’s easy to be discouraged and give up.

I constantly keep in mind our overall goals of raising awareness, providing better care for HD-affected individuals and their families, and finding treatments and a cure.

However, along the way we must tackle the many small, intermediary tasks. When each one of us completes these tasks, together we build a movement – and make a difference.

That’s what today was all about for me.