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)

Bidding farewell to CoQ10: a long-studied supplement proves ineffective in the fight against Huntington’s disease

One of the first and most-studied potential treatments for alleviating the symptoms of  Huntington’s disease has proved ineffective, leading researchers to halt a clinical trial of the substance.

Along with many others in the HD community, I have taken the readily available supplement coenzyme Q10 (CoQ10). As I wrote in a February article about the debate over unproven supplements, the lack of a treatment to slow HD’s devastation of the brain led me to take several of these substances in the hopes of staving off onset (click here to read more).

As reported August 13 by the HD science portal HDBuzz.net, the National Institute of Neurological Disorders and Stroke (NINDS) and the Huntington’s Study Group (HSG) stopped the CoQ10 clinical trial this week because of lack of significant results.

“It seems clear now that coenzyme Q10 does not work for HD,” the HDBuzz article stated. “Looking back, the body of evidence used to decide to test CoQ10 in human patients was fairly limited. In fact, recent efforts to repeat the observation that CoQ10 makes HD mice better have failed.”

According to HDBuzz, the trial known as 2Care, was the “largest ever therapeutic trial for Huntington’s disease.” It had enrolled 609 participants with early HD symptoms from 48 sites throughout North America and Australia. Half received a placebo, while the other half took 2,400 mg of CoQ per day – four times the amount that I have taken.

My supplements, including coenzyme Q10 at far left (photo by Gene Veritas)

A natural substance, CoQ10 is found in all of our cells and helps to turn food into chemical energy. Starting in the mid-1990s, scientists hypothesized that CoQ10 might help alleviate the serious energy deficits found in the brains of HD patients.

In another recent clinical trial, CoQ10 was also shown to have no benefit in stopping early Parkinson’s disease symptoms.

After consulting with several HD specialists, I have decided to stop taking CoQ10. Given the demonstrated lack of efficacy against HD, I see no reason to continue.

Also, although inexpensive over-the-counter varieties of CoQ10 exist, I have taken a medical-grade form that has cost me $1,000 per year. (Health plans do not cover supplements.) I can use that money to relieve strain on the family budget and/or spend it on services such as psychotherapy that help me cope with my situation as an HD gene carrier.

For now, I will continue to take other supplements as detailed in my February article: trehalose, creatine, omega-3 oil, and blueberry extract. However, I also plan to carefully rethink this strategy in consultation with my neurologist and HD specialists. (For a 2012 overview of key supplements and HD by Dr. LaVonne Goodman, please click here.)

A process of elimination

“While the results of this study are disappointing to all of us – particularly the people with HD who faithfully took the drug …  every day for as long as five years, and subjected themselves to blood draws and neurologic exams and questionnaires and surveys as part of their participation in the study – they are nonetheless very important,” Martha Nance, M.D., the director of the Huntington’s Disease Society of America (HDSA) Center of Excellence at Hennepin County Medical Center in Minneapolis wrote in an e-mail response to my request for comment. “Knowing that coenzyme Q10 DOESN’T work will spare the HD families of today and tomorrow the expense of the supplement, and the false hope that it created.”

Dr. Martha Nance: trial result ends "false hope" about CoQ10.

“Nobody said that finding a cure for HD would be easy, but I think that HD patients and families should be enormously proud of their efforts in this study – a commitment that can only help us with the future trials and challenges ahead,” Jody Corey-Bloom, M.D., Ph.D., the director of the HDSA Center of Excellence at the University of California, San Diego, wrote in an e-mail.

The process of elimination in scientific and clinical research is a slow, meticulous, but necessary part of the quest for treatments. Only one in ten clinical trials results in an effective drug. Understanding what doesn’t work expands scientists’ knowledge of the disease.

“We can now divert the resources that were going to be used for the 2CARE study to other studies with a better chance of working,” the HDBuzz article pointed out. “In fact, it’s likely that the next year or two will see the launch of several trials targeting specific mechanisms underlying HD, rather than ‘generally beneficial’ compounds like CoQ10.”

Added Dr. Nance: “We are actively pursuing many other avenues in HD research, and hope that many people will share the wonderful attitude of my patient (I will call her Susan), who said: ‘So, Dr. Nance, I'm sorry that this one is over, but now can I enroll in another HD research study?!’”

Closing out a complex relationship

For me, the end of the 2Care trial closes out nearly two decades of a complex relationship with CoQ10.

I first started taking an over-the-counter variety in early 1996, just weeks after learning of my mother’s diagnosis for HD. With a 50-50 chance of inheriting the gene for a devastating, incurable brain disorder that was inexorably destroying my mother’s personality and ability to think and walk, I grasped for whatever might provide the slimmest of hope.

In the mid-2000s, I started taking a higher grade of CoQ10 along with other above-mentioned supplements in a study under the Huntington’s Disease Drug Works program, which at the time emphasized a “treatment now” approach for a community desperate for solutions. After the study ended, I continued to take the substances and paid for them out of pocket.

CoQ became part of my daily ritual. I broke up the 600 mg chalky, yellow, sweetened CoQ10 tablet into four parts, which I took methodically at breakfast, lunch, and before and after dinner.

Although I knew there was no evidence about CoQ10’s efficacy, I believe it may have had a placebo effect. At 54, I have passed my mother’s age of onset. Now whatever placebo effect might have existed will disappear. In my particular use of CoQ10 and the other supplements, however, an actual placebo effect is scientifically unproven. In addition, scientists are getting closer to understanding the factors (such as a modifier gene) that trigger HD onset.

Throughout my journey with CoQ10, I always viewed it as peripheral at best. I believed that the best hopes lay with the potential remedies such as gene silencing aimed at the root causes of the disease.

Knowing the complexity of HD, I knew that a dietary supplement such as CoQ10 provided no more than a sliver of hope.

As I bid farewell to CoQ10 and the idea that it could delay onset, I’m once again forced to rethink how to survive in the gray zone between my genetic test result and the inevitable onset of an incurable disease. With science as a guide, I'm adjusting what is essentially an attempt at self-treatment.

New California stem cell chief stresses speed and efficiency in search for treatments

A major hope of those facing Huntington's disease (and numerous other diseases) resides in stem cell research.

The new president and CEO of the California Institute for Regenerative Medicine (CIRM), transferring from the pharmaceutical industry, has assumed the helm of the $3 billion organization stressing efficiency, including a pledge to prioritize speedier development of treatments for the many diseases falling within the agency’s scope.

“What I promise I will do is to bring stem cell therapies and treatments to the patients that need them,” C. Randal Mills, Ph.D., chosen to run CIRM by its board of directors on April 30, said in San Diego on June 24 at the third of three “Meet the New CIRM President” events. “That is quite sincerely what I have done my entire career, and the only thing I care about and the only reason I came to CIRM.”

Dr. Mills was introduced by CIRM board chair Jonathan Thomas, J.D., Ph.D. The meeting took place in conjunction with the 2014 BIO International Convention, June 23-26, which showcased the work of leading biotech firms and featured a keynote speech by British business magnate Sir Richard Branson and a moderated Q & A with former Secretary of State and potential 2016 presidential candidate Hillary Rodham Clinton. The convention attracted more than 15,000 participants from all 50 states and 70 countries.

Dr. Mills outlined four questions he said will guide him in decision-making at CIRM.

First, he said, "is whatever we're doing speeding up a treatment reaching a patient?"

Secondly, will CIRM’s activities increase the likelihood of a treatment reaching a patient? There are many “valleys of death,” or dead ends, in stem cell research, Dr. Mills noted.

Third, is CIRM meeting an unmet medical need, as opposed to a condition already successfully dealt with by other medical means?

Fourth, is CIRM doing all this efficiently?

Randy Mills speaks to disease advocates and stem cell industry representatives in San Diego (photo by Gene Veritas).

Taking care of patients

Dr. Mills said his patient-oriented outlook started during his undergraduate studies in microbiology and cell studies at the University of Florida, in Gainesville.

“During that time I worked as a medic in the emergency room,” he told the audience. “I saw and dealt with a lot of patients and got a pretty good sense of what patient care was like and delivery was like.”

Dr. Mills obtained his Ph.D. in drug development, also at the University of Florida. After that, he worked for the university as a specialist in orthopedic transplants. With a partner, Jamie Grooms, he started a company within the university specializing in spinal fusion, one of the most common of orthopedic procedures.

In 1995, the two “spun out” the company from the university, calling it University of Florida Tissue Bank. That year the company had $1 million in revenues, with only six employees. Five years later, when the firm went public, it had 550 employees and annual revenues of $120 million.

“More importantly, (we were) producing regenerative medicine solutions for patients all across the United States on the scale of hundreds of thousands of implants, and better implants, a year,” Dr. Mills explained.

“It was during that time that I really learned a lesson. And the key lesson is: if you take care of patients, then your business is going to follow. If you don’t take care of the patients, there is nothing you can do in order to get your business to come along.”

Randy Mills (Osiris photo)

Key achievements at Osiris

In 2004, at the age of 32, Dr. Mills was recruited to become the president and CEO of Osiris Therapeutics, Inc., a Columbia, Md.-based company that commercialized the world’s first stem cell product, Osteocel, for bone regeneration. According to Mills, that product has brought a total of $1.5 billion in revenue to Osiris.

Under his leadership, in May 2012 Osiris received approval to market the world’s first systemically infused stem cell drug, Prochymal, which it developed to combat pediatric acute graft-versus-host disease. (It was approved in Canada but is also available in the U.S.; click here to read more.)

This condition occurs in patients receiving bone marrow transplants that reject the person and attack the body.

“Patients will literally peel out of their skin,” Dr. Mills said, describing the horrors of the condition. Patients with the condition have a life expectancy of only 87 days, he added.

With Prochymal, patients got better two-thirds of the time, he said.

Dr. Mills attributed Osiris’s success to its intense focus on patients.

“The board room is covered with pictures of our patients,” he said.

“That’s my mission with CIRM,” he continued. “We’re going to focus on the patients, and everything else is going to come along. If you get a sense of urgency from me, it’s because, if a life expectancy of a disease is 87 days, missing a month or two months or three months are actually real patients dying.”

Putting criticisms of CIRM in perspective

The stem cell board’s selection of a new CEO with long experience in the drug industry takes place a decade after California voters created CIRM by approving Proposition 71, the California Stem Cell Research and Cures Act.

According to CIRM’s statistics, so far four clinical trials directly funded by the organization have taken place – including an observational study of Huntington’s disease patients at the University of California, Davis, the basis for a potential CIRM-supported treatment trial envisioned by Dr. Vicki Wheelock and Dr. Jan Nolta (click here to read more).

Six additional trials for different conditions are based on “discoveries made by our grantees when they were carrying out CIRM-funded research,” CIRM reports (click here to read more).

According to Kevin McCormack, CIRM’s senior director for public communications and patient advocate outreach, five more directly funded trials for various diseases will start by the end of 2014.

CIRM’s efforts have not yet produced a drug, although one or more treatments could arise from the clinical trials.

Some in California have criticized CIRM’s performance. The San Francisco Chronicle, for instance, editorialized that CIRM “hasn’t lived up to its hype” and has compiled a “decidedly mixed” record, although it recognized that California voters had “outsize expectations when they passed Prop. 71.”

The Chronicle further noted that “it’s been a struggle to get the agency to use the best organizational practices. In 2012, a blue-ribbon committee of the National Academy of Sciences released a report after a yearlong review that found conflicts of interest on the CIRM board that threatened to ‘undermine respect for its decisions.’ It also found significant flaws in the agency’s grant-approval process.”

The editorial added: “Progress on stem cell research has been significant – but it’s been the progress of the tortoise rather than the hare.”

In general, news coverage of CIRM has been sporadic. After all, news outlets typically don’t report on the work of scientists in the trenches.

In this blog, I have provided frequent coverage of HD science as well as related stem cell research. In my 15 years writing about HD science, I’ve learned that scientific progress is slow by nature. It’s not just the CIRM projects that take a long time to produce results.

From my standpoint, stem cell science has produced a “growing array of possibilities” for treatments and the “potential for a new era in human health,” as I noted after attending the 2013 World Stem Cell Summit (click here to read more).

Producing treatments is also extremely expensive. According to Jim Greenwood, president and CEO of the Biotechnology Industry Association, which organized the Bio Convention, developing a new drug in the U.S. costs an average of $1.2 billion. CIRM and/or its affiliated researchers will need to partner with the pharmaceutical industry to bring treatments to market.

In the HD community, we earnestly hope for stem cell treatments, but we’re also aware that a “cocktail” of different approaches (like gene therapy) will likely be needed to deal with the complexities of the disease. We’re rooting for all the researchers to find keys to treatments.

Crucial experience with clinical trials

With the need to show results, it’s not surprising the CIRM board chose a new CEO from the business world.

As noted by David Jensen, author of the blog California Stem Cell Report, CIRM’s previous two presidents, Zach Hall, Ph.D., and Alan Trounson, Ph.D., came from “largely academic and non-business backgrounds…. Decisions are likely to come faster under Mills.”

In his introduction of Dr. Mills at the San Diego meeting, CIRM board chair Dr. Thomas said that the new CEO met the many qualifications sought by the organization, including familiarity with the process of running stem cell clinical trials and seeking approval of drugs from governmental agencies.

“Very few people can say they’ve had more experience in clinical trials in stem cells,” Dr. Thomas said. “Very few people can say they’ve had more experience with the regulators, not just from the U.S., but from other countries as well.”

Randy Mills (left) and CIRM board chair Jonathan Thomas (CIRM photo)

The board also sought someone familiar with CIRM. Dr. Mills has spent the last five years as a reviewer of proposals made to CIRM by stem cell researchers seeking funding. (Click here to read more.)

During the audience Q & A, one woman asked Dr. Mills what he would do to make the grant review process more “transparent.”

Recognizing that the process wasn’t “perfect,” Dr. Mills nevertheless said he believed it was “pretty good” and already “remarkably transparent,” with world experts involved in the reviews. He reminded the audience that no “divining rod” exists to pick perfect projects. He added that he will work for quicker approval of worthy applications.

Keeping CIRM running

Jeanne Loring, Ph.D., a leading expert on stem cells and Parkinson’s disease at The Scripps Research Institute in San Diego, wanted to know how Dr. Mills would prioritize CIRM spending from now through 2017, when the last of the agency’s grants will be made and the original CIRM allocation of $3 billion might run out.

The agency still has about $600 million in uncommitted funds. In all, $1.5 billion of its $3 billion budget has yet to be spent, as many budgeted projects remain in progress.

“Let’s be careful on speculating on when CIRM is going to run out of money,” Dr. Mills said in response to Dr. Loring’s question. “That (2017) would be the absolute earliest. This is an important thing for people to understand: in order for that date to be true, things have gone incredibly well. Everything we funded, 100 percent of it, has worked. If that ‘17 date happens, I’m a happy guy, because we are rattling off diseases left and right.”

Dr. Mills explained that CIRM does “milestone-based funding.”

“So we’ll fund your project, but if you don’t hit your milestone, if it’s not working, we stop funding,” he continued. “That seems like a pretty good idea. So the projections on these running out of money is assuming that everything is going along. Everything’s going along, and we can’t get California to say, ‘Let’s keep doing it’? In a more practical sense, we’re not going to run out of money by then, and everything’s not going to work perfect. My job is to run CIRM as efficiently as we possibly can to develop treatments.”

According to spokesperson McCormack, the CIRM board can still redirect funding from the $1.5 billion as yet unspent. If a project comes in under budget, CIRM can also redirect savings to other projects, he added.

Some stem cell advocates such as Don Reed, who served on the executive board for the Prop 71 campaign, are already advocating a second round of CIRM funding to be requested from the state by way of another ballot proposition to be put before the voters. (You can watch Reed, HD advocate Judy Roberson, and children’s neurological disorders advocate Alex Richmond speak about their experiences by clicking here.)

Dr. Thomas has also spoken publicly about seeking private sources of funding for CIRM. In this vein, Dr. Mills’ experience in capital markets – one of the sought-for qualities in a CEO noted by Dr. Thomas – could prove helpful.

"California (undertook) a very important task in creating a funding stream for stem cell research," Clinton, referring to CIRM, said during her Q & A at the Bio Convention. "Other states have followed suit, when it looked as though the federal government would not be doing that. States have a role to play, but we need a national framework."

‘Our urgency for cures’

Huntington’s disease advocates participated in the “Meet the New CIRM President” events in San Diego as well as Los Angeles and San Francisco.

One of those participants, veteran advocate Frances Saldaña of Orange County, sees Dr. Mills’ appointment as a positive step.

“I really liked Randy Mills,” Saldaña, a mother of three children stricken with juvenile HD, told me in an e-mail about her encounter with Dr. Mills at the June 10 Los Angeles meeting. “I feel that he really understands our urgency to find cures.”

Saldaña’s daughter Margie Hayes – who became one of the very first HD patients to advocate for CIRM support for Huntington’s stem cell research when she spoke at a December 2007 CIRM board meeting – succumbed to the disease on February 7. Hayes had just turned 44. She is survived by her husband Craig and two teenaged children.

Saldaña’s husband also died of HD, which has afflicted several other members of her extended family. She was recently presented the 2014 Living Our Values Award by Michael Drake, the chancellor of the University of California, Irvine (UCI), for her work in HD community service. Saldaña is the founder of HD-CARE, an Orange County care organization affiliated with UCI’s Institute for Memory Impairments and Neurological Disorders.

Saldaña said of Dr. Mills: “In the case of HD families, he completely understands that we're in a race against time, as our families are dying.”

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

Woody Guthrie, Huntington’s disease, and our duty to improve caregiving

By revisiting the huge, long-abandoned New Jersey mental hospital where radical songwriter and performer Woody Guthrie struggled for five years with the symptoms of Huntington’s disease, photographer and author Phillip Buehler provides us with a valuable new perspective on the crisis in care for people disabled by neurological disorders.

In Woody Guthrie’s Wardy Forty: Greystone Park State Hospital Revisited (Woody Guthrie Publications, Inc., 2013, 162 pages), Buehler, a specialist on derelict buildings, captures the rooms, corridors, and grounds of the psychiatric facility that housed Guthrie between 1956 and 1961. It had over 6,000 patients and had some 2,000 employees at its height in the 1960s.

A companion volume, Woody Guthrie’s Wardy Forty: The Interviews, provides background from those who knew Guthrie or are involved in the campaign against Huntington’s. (Click here to purchase the books.)

Woody Guthrie (above) and the new books about his time at Greystone Park State Hospital (below) (photos from www.woodyguthrie.org)

Utterly debilitated and unable to speak, Woodrow Wilson Guthrie, the composer of “This Land is Your Land,” died of Huntington’s at Creedmoor State Hospital in Queens, NY, in October 1967 at the age of 55.

Today the United States has an estimated 5.4 million Alzheimer’s disease patients, and an additional 14.9 million family members and friends cope with the disease as caregivers or in other ways. About one million people suffer from Parkinson’s disease.

Huntington’s disease (HD) patients number 30,000, with an additional 150,000-250,000 at risk. The government classified HD as an “orphan,” or rare, disease because of the relatively small number of people affected (fewer than 200,000). Numerous other disorders have similar symptoms. By mid-century, as many as 120 million people worldwide will suffer from dementia.

The world must shoulder a massive caregiving burden. Most people affected by such illnesses will require care ranging from in-home assistance to admission to a nursing home.

While researchers have made strides studying the symptoms, causes, and treatment of these conditions, caregiving has not advanced. Professional caregivers typically earn very low wages and receive little training. Even many doctors cannot properly diagnose rare disorders such as HD.

“Long term care remains a scandal in the United States,” Alice Wexler, Ph.D., a board member of the HD-related Hereditary Disease Foundation and author of two books on the disease, writes in a brief history of the disease included in Buehler’s book. “Persons living with HD and their loved ones – and all those with chronic neurodegenerative and psychiatric illnesses – still struggle mightily to find appropriate and affordable support and care, at home while they are still able, in facilities when they are not.”

In a case that shocked the HD community, in May 2013 a 49-year-old, late-stage HD patient was allegedly strangled in an Oregon nursing home by another patient whom police described as suffering from “severe dementia.”

To complicate matters further, the Genetic Information Nondiscrimination Act does not provide protection to people seeking life, disability, and long-term care insurance. Thus, as genetic testing, including full DNA sequencing, promises to become ubiquitous, people run the risk of not getting the coverage they will most need as they live ever longer lives. Only three states (California, Oregon, and Vermont) prohibit this type of discrimination.

Lives instantly transformed

My own family has struggled with Huntington’s disease since the late 1980s, when my mother Carol Serbin started having strange swings in mood. A few years later, she developed chorea, the involuntary movements most Huntington’s sufferers develop, causing some to appear as if they are dancing.

Nobody in the family understood what was wrong until in 1995 a neurologist suspected Huntington’s. Just two years before, researchers had concluded a two-decade quest to find the disease-causing gene, which they called “huntingtin,” like the disease named for the American physician George Huntington.

In 1872, Dr. Huntington published an article describing HD’s symptoms and definitively establishing it as a genetically transmitted condition. Everybody has this gene, which is essential for life, but when it expands beyond its normal size, it causes brain cells to die. The discovery of the gene allowed for a definitive test for the disease, though, unfortunately, science has yet to provide effective treatments, much less a cure.

Receiving the news of my mother’s diagnosis the day after Christmas 1995, my wife Regina and I saw our lives transformed before us in an instant. With no treatment or cure, HD was fatal. All children of an affected parent had a 50-50 of inheriting the condition. Most people experience disease onset between the ages of 30 and 50, and everybody with a certain degree of gene expansion or greater will develop the condition.

My mother’s diagnosis and the fear that I might carry the genetic expansion compelled me to fight back in any way I could. Regina and I immediately started attending the local support group of the Huntington’s Disease Society of America (HDSA), and I became an HDSA advocate.

I began writing about my experiences in this blog. Because of fear of genetic discrimination, until recently, I performed all of this behind the scenes, for example writing under a pseudonym, Gene Veritas.

The fear that I carried the mutation led Regina and me to postpone starting a family. By 1999, however, we agreed to try. First, I decided to get tested. I was especially worried about transmitting the mutation, because sometimes men pass on an even longer expansion, resulting in an early-onset form known as juvenile Huntington’s.

Our worst fears were confirmed: I had the same expansion as my mother and would likely develop the disease in my forties or fifties.

We then embarked on the most difficult decision of our lives: the testing of our daughter in the womb (so-called preimplantation genetic diagnosis was not yet available). After weeks of waiting for the results, we received the happiest news of our lives: our “miracle baby” was HD-free! Today Bianca is a thriving middle school student.

The genetic mirror

Throughout this period, I juggled my roles as college professor, father and husband, and Huntington’s disease advocate – all while watching my mother’s inexorable decline. In addition to her psychiatric symptoms and chorea, she suffered from the third manifestation of the HD triad: cognitive loss and dementia.

“Each encounter with my mom became a view into a nightmarish genetic mirror,” I wrote to a physician friend who included my story anonymously in a September 2005 Washington Post article on HD. “I watched her body jerk, head bob, and fingers fret. One night I found her wandering around our house confused and half naked. Within a year she lost most of her capacity to speak. She ate clumsily with her hands.”

Around that time, because my “HD warrior” and caregiver father Paul could no longer care for my mother at home, he placed her in a nursing home. She died quietly in her sleep in February 2006, at 68.

Paul and Carol Serbin (photo by Gene Veritas)

Finally seeing the beauty

Following Guthrie through the pages of Buehler’s books, I was prompted to reflect on my relationship with my mother as she struggled with HD as well as on how our system of caregiving must improve.

Disease communities are used to emphasizing the devastation of the their particular conditions. The devastation is real. But there is more to the person than the illness. I regret not having the emotional strength and presence of mind to have seen my mother more as a person and less as a mind and body racked by the symptoms of Huntingon’s. Because I had tested positive for the mutation, often “my fear of HD kept me from sitting down with her and attempting to converse,” I once wrote.

In the “Foreword” to The Interviews, Guthrie’s daughter Nora recalls her own hesitancy as a 15-year-old to reach out to her father and how she ultimately learned to appreciate the man who, despite HD, understood his daughter’s feelings, a man who possessed “twinkling eyes and a mischievous grin, releasing us all to live our own lives completely and wonderfully, taking each day and each situation as it comes.” Her father “lived with this disease, but he never became Huntington’s disease.”

“As I turn these pages, I can finally see a beauty that has taken me over fifty years to recognize,” Nora writes of Buehler’s photographs of the hospital where she, her mother Marjorie, and brothers Arlo and Joady visited Guthrie on the weekends and held picnics on the lawn, the children often playing in a large tree their father dubbed the “magicky tree.” “These images are merely ruins, the gross leftovers, the little pieces, chipped and peeling fragments of a life felt and lived so vividly and boldly.”

Discrimination and misdiagnosis

The Guthries’ story became my family’s story, too. I remembered how I had travelled from my home in San Diego to visit my mother in the nursing home in suburban Cleveland shortly before she died. She shared a room with a woman paralyzed from the neck down. The attendants tried to feed my mother but didn’t give her much more than a few spoonfuls before quitting. Always patient, my father had done a better job of feeding her when she was still at home. He would feed her once a day at the nursing home, too. Still, she was losing energy, slowly slipping towards death.

As the books recount, Guthrie faced the kind of discrimination still faced by HD people today: police officers and member of the general public often believe that HD people are drunk. In 1956, Guthrie was picked up by New Jersey state troopers, who thought he was a vagrant. Only after a phone call from a friend did the troopers comprehend that he needed medical attention.

At first, the medical personnel at Greystone refused to believe Guthrie’s claims to have written thousands of songs. Instead, they described him as “delusional” and diagnosed him as a paranoid schizophrenic. HD is frequently misdiagnosed, in part because many doctors have little or no knowledge of the disease.

“Paranoid schizophrenia was a very common misdiagnosis – as were others including Parkinson’s disease, Alzheimer’s, all kinds of psychiatric illnesses and people were just locked away,” says Dr. Michael Hayden, a world-renowned HD expert and leader in the quest for treatments, in an interview with Buehler.

It took years to discover the cause of my mother’s difficulties. She, too, had received different diagnoses, and some of her doctors seemed indifferent or unwilling to get her to the right specialist. At first she was put on Haldol, an anti-psychotic also used to try to control chorea in HD. I quickly learned, however, that neurologists who understood HD avoided Haldol because of negative side effects, so we got her off of it as quickly as possible.

A difficult environment

The first two images in Buehler’s work are Guthrie’s Greystone intake photographs, which Buehler found in the basement of the admissions building, shown on the next page in a recent shot by the author. Later we come across Guthrie’s bed in Ward 18 of the clinic building.

Images of Greystone Park State Hospital and a letter written there by Woody Guthrie (photos from www.woodyguthrie.org)

“I remember one time walking through the entire ward with beds lined on both sides to get to my father’s bed at the very end,” Nora recalls in the accompanying text. “The walk seemed to take forever. All around us were strange people yelling, talking to themselves, uninhibited or somber.”

I’ve learned that most HD patients are mixed in with individuals with other conditions in facilities where personnel have little, if any, knowledge of HD. HD family members must often educate health personnel about the disease. Perhaps my mother would have lived longer had there been a nursing home with appropriate enrichment activities for her condition.

Guthrie lived most of the time in Ward 40, which, with his typical mirth, he nicknamed “Wardy Forty,” as in the 1956 letter that appears in the book. Although HD by this time had robbed Guthrie of his ability to play guitar, he continued to write frequently, although ever less legibly.

My mother was always in charge of balancing the family checkbook and writing Christmas cards. For a while after HD struck, she continued these activities. She used a ruler to make perfectly straight lines on which to write addresses. She eventually lost the ability to write.

A caregiver’s dedication

In a 1956 play titled “My Forsaken Bibel [sic],” written at Greystone, Guthrie responds to a friend’s question about how he inherited HD from his mother: “Hit my mother Nora Belle when she was about 40. Made her just go into such violent fits and such violent kinds of spasms that, well, she just wreckd [sic] and just wracked every single house we did live in. My cardiographer over yonder in Brooklyn just told me my mother’s chorea sorta passled [sic] on to me here.” Nora Belle died in an Oklahoma mental hospital in 1929.

My mother loved to sew. I remember the Halloween costumes and other clothing she made for me. One day she just stopped. She left scores of patterns unused. Like Guthrie, I love writing. I have already passed my mother’s age of onset. How much longer before HD erodes my ability to express myself? Will I need to go into a nursing home? Will a treatment be found?

Marjorie loved and cared for Guthrie despite the fact that they had separated about a decade earlier because of strains over the disease. They eventually divorced. Near the end of Wardy Forty, Buehler places photographs of the couple at her Queens home, where she would take her husband for visits.

“She stripped him of his clothes and scrubbed him in the bath, sprinkling him with talcum powder and singing, 'Doesn’t he smell sweet now!'” Nora recalls in the accompanying text. “She would wash and iron his clothes, sew up the tears, and dress him like a mother dressing her child for a first day of school.”

Once my father, daughter, and I went with my mother to a park. My mother needed to use the rest room. We had to lift her from her wheelchair and maneuver her clumsy and unresponsive body into the stall. It was like moving dead weight. She nearly fell. When she was finished, we had to repeat the process in reverse. Later, in her final months of life in the nursing home, my father visited her every day. Dejected by her death, his own dementia worsened dramatically. A year after she died, he started taking a large, beautiful, framed picture of her wherever he went, including restaurants. In 2009 he, too, died in a nursing home

Time to stop ‘throwing away’ people

The final two images of Buehler’s book are of Guthrie’s Greystone discharge photos from April 1961, which contrast with the 1956 frontal intake photo. Initially, Guthrie looks into the camera. His expression is sad, but he appears relatively healthy. Upon discharge, however, he casts his eyes downward, typical of the difficulty HD-affected individuals have with visual focus. He appears to have lost much weight.

Arlo was 19 when his father died. That same year, he released the song “Alice’s Restaurant,” a protest of the Vietnam War draft. In 1969 he starred in the Hollywood movie based on the song and performed at the Woodstock Festival. Arlo himself never tested for HD and has not shown symptoms.

In Wardy Forty, Arlo has a strong message about Greystone and its residents: “These places were built so that they wouldn’t be a burden on society. You could throw away your odd child, put him in one of these towns, almost like sending people to Australia from England years ago. Penal colonies. And so it’s no wonder why they ended up in this sort of notoriously bad scene. They were set up from the very beginning to be away from the world, and not be part of it. Greystone is a real monument to that.”

The idea behind Greystone still largely governs our outlook on care for the neurologically disabled.

People across the country are acting to correct the situation. Maria Shriver and former Supreme Court Justice Sandra Day O’Connor – both lost loved ones to Alzheimer’s – have warned the public of the Alzheimer’s “tsunami” about to hit America.

In Vermont, HD activists successfully advocated for state laws preventing inappropriate transfers of nursing facility residents and requiring public assistance for home-based and community-based care. At the national level, HDSA is pressuring Congress and the Social Security Administration to update long-outdated and inaccurate disability criteria for HD and to waive the two-year waiting period for patients to receive Medicare benefits.

Responding to press reports of corruption and abuses and requests from advocates, California state legislators in January announced twelve bills aimed at addressing the inadequate care in the state’s assisted living facilities and nursing homes.

Indeed, the time has come to develop a more compassionate society by valuing both the person cared for and the caregiver.