Continued progress, but also caution, in the fight against Huntington’s disease

CHDI Foundation’s 14th Annual Huntington’s Disease Therapeutics Conference gets under­­ way today in Palm Springs, CA, in the wake of key developments in the search for the first HD treatments.

On January 28, pharma giant Roche announced that it had enrolled the first participant in GENERATION HD1, its historic global Phase 3 clinical trial of a gene-silencing drug that, if successful, could slow, halt, and perhaps even reverse HD symptoms. (Click here to read the announcement to the HD community by Roche ).

In the coming months, Roche aims to enroll a total of 660 clinical trial volunteers in 15 countries. They will receive either the drug (called RG6042) or a placebo in monthly spinal taps over 25 months.

The start of the trial comes less than a year after the presentation of the impressive Phase 1 trial results at last year’s Therapeutics Conference. RG6042 significantly reduced the levels of the mutant huntingtin protein in the cerebrospinal fluid of the clinical trial volunteers. Because of those results, Roche took the unusual step of skipping a Phase 2 trial and going directly to Phase 3.

Roche’s announcement follows a record year for new drug approval by the U.S. Food and Drug Administration (FDA), with 59 drug approvals overall, noted George Yohrling, Ph.D., the senior director of mission and scientific affairs for the Huntington’s Disease Society of America (HDSA). The previous record was 53 in 1996.

Of last year’s approvals, 34 involved orphan conditions like HD (fewer than 200,000 patients) – a sign, said Dr. Yohrling, that the pharmaceutical industry has not ignored those disease communities. He spoke in a January 16 webinar reviewing progress in HD research in 2018.

Roche to buy Spark

On February 23, The Wall Street Journal reported that Roche had agreed to pay $4.8 billion to acquire Spark Therapeutics, Inc., a Philadelphia-based biotech firm focusing on gene therapy approaches to genetic diseases, including HD. Spark’s co-founders include HD researcher Beverly Davidson, Ph.D.

With a record 360 participants from around the world, the CHDI conference opens this evening at the Parker Palm Springs hotel and runs through February 28. At the conference, I hope to obtain comment from Roche officials about how the acquisition could potentially expand Roche’s approaches to treating HD. Spark has engaged in pre-clinical HD research.

Above, scientists visit the CHDI Resource Fair at the 14th Annual HD Therapeutics Conference. Below, Gene Veritas (aka Kenneth P. Serbin) at the Parker Palm Springs (photos by Gene Veritas).

Exciting announcements about other trials

On January 22, the Dutch-American company uniQure announced that it had received approval from the FDA to start the first-ever HD clinical trial that uses a virus injected into the brain carrying a gene therapy agent to reduce the amount of harmful huntingtin protein. Viruses are used in vaccines and to treat cancer. They are under study for use in HD and other diseases. 

Unlike Roche’s RG6042, which would require long-term and probably lifelong treatment, uniQure’s gene therapy could permanently fix the problem of HD by “altering human DNA or inserting new genetic instructions into human cells,” observed HDBuzz.

However, it also noted that “gene therapy is a high-risk high-reward strategy. The benefits could be long-lasting – but so could any side effects.”

In this Phase 1/2 clinical trial, uniQure will primarily test safety and tolerability but also whether its drug is working as designed. It plans to start enrolling clinical trial volunteers in the U.S. in the second half of this year.

In late January, the California Institute for Regenerative Medicine (CIRM), the state’s voter-approved multi-billion stem cell initiative, announced a $6 million grant to prepare the way for a potential HD stem cell clinical trial. CIRM awarded the grant to the lab of Leslie Thompson, Ph.D., of the University of California, Irvine. The therapy could involve the transplanting of stem cells converted into neural (brain) stem cells shown in HD animal models to improve the function of compromised brain cells.

"Based on our pre-clinical studies in mice, human neural stem cells are highly beneficial, reducing the accumulation of a toxic form of the mutant huntingtin protein and improving HD symptoms and impaired electrical currents in the brain," Dr. Thompson explained in a news release.

FDA delays Wave trials

Another company’s plans have been slowed. The FDA has delayed two Phase 1 clinical trial by Wave Life Sciences using a drug – an antisense oligonucleotide – similar to Roche’s RG6042.

Whereas RG6042 reduces the amount of both mutant and normal huntingtin protein, Wave’s drugs target only the mutant.

“In the United States, we received approvals to proceed with the single-dose portions of both trials,” a February 6 Wave prospectus states. “However, the FDA indicated to us that we cannot progress to the multiple-ascending dose portions of these trials in the United States unless we conduct an additional preclinical [animal] study and present the resulting data to the FDA for its review.”

Realistic expectations

The news about Wave might be a cautionary tale for the HD community about realistic expectations. Only ten percent of clinical trial projects result in a drug reaching the market.

Alzheimer’s disease is another case in point. Over the past ten years, all 25 Alzheimer’s clinical trials have failed, noted Jody Corey-Bloom, M.D., Ph.D., the director of the HDSA Center of Excellence at the University of California, San Diego (UCSD), during her annual HD research update last October at the local HD support group.

As Dr. Corey-Bloom explained, most of those Alzheimer’s trials successfully removed seemingly harmful plaque from the brain, but they didn’t cure the disease. 

Such plaque isn’t a factor in HD, however, perhaps increasing hope that the Roche Phase 3 trial has a better chance of producing effective results, she observed. Dr. Corey-Bloom’s well-regarded UCSD clinic is one of the sites for GENERATION HD1.

An end to the ‘wait and see’?

In her presentation, Dr. Corey-Bloom addressed several of the key questions about GENERATION HD1 that have emerged in the HD community, including concerns about the injection of the drug by spinal tap (lumbar puncture).

She noted that spinal taps are a regular part of treating a condition known as pseudotumor cerebri, which produces severe headaches and, if left untreated, blindness. Patients get monthly spinal taps.

“We’ve had people that have probably done lumbar punctures monthly for several years, and they seem to do okay,” she commented.

She was optimistic that, if GENERATION HD1 is successful, Roche and physicians will seek alternatives to spinal taps. They will also pursue expanding access to the drug to presymptomatic gene carriers, she added. (That includes me.)

Dr. Corey-Bloom ended on a positive note.

“I’m always talking about things that will eventually come,” said of previous talks, in which she has cautioned the HD community against unwarranted enthusiasm. “Now we actually have clinical trials, and we have clinical trials that look like they are going to be effective. That’s probably the strongest statement that I’ve made, because I’m always trying to tell people, ‘Let’s just wait and see.’”

However, with the Alzheimer’s trials in mind, Dr. Corey-Bloom also reminded the audience that there is no guarantee GENERATION HD1 will actually affect the disease.

She crossed her fingers for good luck. We in the HD community will need to continue our hard work collaborating with her and the many other researchers engaged in the quest for treatments.

You can watch Dr. Corey-Bloom’s presentation in the video below.

A key Huntington’s disease trial remedy gets Orphan Drug Designation, as yet another young life is cut short

Ionis Pharmaceuticals, Inc. (formerly Isis Pharmaceuticals) has achieved another milestone in its search for a treatment for Huntington’s disease: on January 5 the company announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for its gene-silencing drug, currently under study in a clinical trial in Europe and Canada.

The FDA designation, intended to facilitate development of the test drug IONIS-HTT_Rx  by offering financial incentives and assistance, could not come at a better time. Huntington’s disease patients – like 18-year-old Terry Leach of San Diego, who died the morning of January 2 – continue to succumb to this devastating, untreatable disorder.

“Although the toxic protein produced from the huntingtin (HTT) gene in HD patients has been a target of interest for many years, IONIS-HTT_Rx is the first therapy to enter clinical development that is designed to treat the underlying cause of this fatal disease,” Frank Bennett, Ph.D., Ionis’s senior vice president of research, said in a company press release. “The granting of Orphan Drug Designation in both the U.S. and Europe highlights the significant need for a drug that could transform the treatment of HD.”

HD-affected Phase I clinical trial volunteers in London received the first dosing of IONIS-HTT_Rx in the October 2015 (click here to read more). IONIS-HTTRx could potentially reduce, partly reverse, and even prevent symptoms.

Likely ending in 2017, Phase I is testing primarily for safety and tolerability. If it is successful, Phase II and III trials measuring the drug efficacy’s would ensue. Together the three phases of a trial typically take at least five years. If the trial is successful, a drug could become available around 2020.

Frank Bennett, Ph.D. (photo by Dr. Ed Wild)

Increased dialogue, helpful benefits

“We were pretty excited to get Orphan Drug Designation,” Kristina Bowyer, Ionis’s executive director of patient advocacy, said in a phone interview on January 5. Ionis is based in Carlsbad, CA.

The designation means that the FDA recognizes “the severity of the disease and the limited population,” she noted.

The designation creates an opportunity for increased dialogue between Ionis and the FDA regarding the IONIS-HTT_Rx clinical trial, Bowyer explained.

Such extra communication can help resolve the unique issues of orphan disease trials. Because an orphan disease like HD involves fewer than 200,000 patients and very specific approaches to treatments, the design of clinical trials is atypical, Bowyer said. The smaller number of potential volunteers also means that the FDA might have to approve a smaller than normal trial, and sometimes perhaps even a faster trial, she added.

“It’s an area where our technology is well-suited,” Bowyer continued, referring to the antisense oligonucleotides that form the backbone of all Ionis drugs. “We have been able to focus on several rare diseases with a known target.”

By law, as outlined in the press release and in an e-mail from Bowyer, the Orphan Drug Designation includes significant financial benefits for Ionis: seven years of market exclusivity in the U.S. if the FDA approves the drug, tax credits related to clinical trial expenses, FDA assistance in clinical trial design, and a waiver of Prescription Drug User Fee Act filing fees – over $1 million per drug as of fiscal year 2009.

“These benefits help manufacturers recover the costs of developing a drug for small numbers of people,” Bowyer wrote. The Orphan Drug Act was signed into law in 1983.

Kristina Bowyer (photo by Gene Veritas)

Trial ‘moving along well’

In IONIS-HTT_Rx, HTT stands for the gene huntingtin, and Rx for medical treatment. The train has just recently begun, so, Ionis has reported no official update at this time.

“Everything is moving along very well,” Bowyer said.

The new name

Ionis has also adapted well to its name change, announced on December 18, 2015, in response to concerns about confusing the name Isis Pharmaceuticals, Inc., with the acronym “ISIS” used in the English-language media for the Middle Eastern terrorist organization, the Islamic State. Isis Pharmaceuticals was founded in 1989.

“We want people when they hear or say our name to think about the incredible drugs we’re developing and not a terrorist group,” Wade Walke, Ph.D., vice president of communications and investor relations, told the press.

Ionis chose its new name based on employee suggestions.

“It seemed to me that everybody came together and decided that Ionis was a nice-sounding, feeling name, as soon as someone hit on it,” said Stanley Crooke, M.D., Ph.D., Ionis’s chairman of the board and CEO. The new moniker is a so-called empty vessel name and has no inherent meaning other than what the company does, he added.

Said Dr. Crooke: “We’re here for the patients. We’re not here for our name.”

(Disclosure: I hold a symbolic amount of Ionis shares.)

The Ionis logo

Too late for Terry, other ‘HD angels’

I remember that Dr. Crooke spoke the same phrase – “We’re here for the patients” – when I met him briefly during one of my first visits to the company in the late 2000s.

I also remember visiting Terry Leach on Labor Day 2015. He was slowly but inexorably slipping away from the ravages of juvenile HD, a particularly devastating form of the disease (click here to read more about my visit).

Nevertheless, I was still shocked by his death on January 2.

What a horrible time to lose a family member. New Year’s will forever remind Terry’s mother Angela and his siblings of his passing.

My immediate reaction that morning was one of intense anger.

No 18-year-old should die!

Having had the privilege of knowing Terry and his family, I felt that I had failed as an advocate to speed the progress towards treatments.

Why hadn’t the Ionis trial come in time to save Terry and the other “Huntington’s disease angels” who have passed in recent weeks?

I know that HD researchers may have similar thoughts, as they work with the specter of this killer disease ever looming.

Terry Leach (family photo)

Keeping the faith

Later in the day, knowing that I needed to transcend my anger and sadness, I recalled that a new year always brings hope. As I took a long, strenuous walk with my dog through our hilly neighborhood, I renewed my resolve to fight HD in 2016.

I spoke to Angela a few times that weekend. Instead of a wake and church service, the family will hold a remembrance for Terry at the family home on January 16. A Christian minister will preside.

At Angela’s request, I wrote some words for the back of the remembrance cards she’s having made: “With his infectious smile and fortitude, Terry set an example for all to follow. His life was short, but full of love and joy. He is now free to walk with the Lord.”

Understandably, Angela was too drained to talk much. She did confirm that Terry – despite his inability to talk, his confinement to a wheelchair, and years of ingesting food through a feeding tube – had achieved his high school diploma. He had attended school through mid-2015, receiving assistance in a program for the disabled.

I asked Angela if she had any words for the HD community.

She said: “Just to keep their faith.”

Angela Leach in 2012 holding artist Lee Ellingson's drawing of her son Terry as "SuperTerry," the superhero who knocks out Huntington's disease (photo by Gene Veritas)

Can we afford the costs of orphan disease treatments?

Millions of people in America suffer from rare, or “orphan,” diseases, conditions defined by the government as affecting fewer than 200,000 people. With an estimated 30,000 affected individuals, Huntington’s disease is one of the more common of these disorders.

The pharmaceutical industry has largely ignored these diseases, which number several thousand, because each disease promises too few customers/patients to enable companies to recoup investments in drug research and development and therefore generate a profit. The market usually doesn’t work for people with these diseases.

News about a lawsuit by Arkansas cystic fibrosis (CF) patients against the state’s Medicaid program for its refusal to pay for a highly effective but extremely expensive drug – Vertex Pharmaceutical’s Kalydeco – shined light on this predicament.

In an article titled “The $300,000 Drug,” New York Times columnist Joe Nocera recognized Kalydeco as a “wonder drug” but questioned whether the country can afford the personalized medicine approach that enables scientists to design specialized treatments for very small and specific groups of patients.

With an annual wholesale cost of $311,000, Kalydeco was developed for a subgroup of about 1,100 CF patients with specific genetic mutations. The subgroup numbers about 2,150 patients worldwide in an overall CF population of 70,000 individuals.

“Because patients will likely be taking the drug for the rest of their lives, it could cost millions of dollars to keep just one patient on Kalydeco,” Nocera speculated. “That raises another important question about the coming of personalized medicine. How are we, as a society, going to pay for it?”

Same question for the HD community

The HD community could face this very same question. Because the U.S. has only 30,000 HD patients and 150,000 to 250,000 people at risk of carrying the gene, a potential treatment could cost a lot.

Boston-headquartered Vertex has sought to develop HD treatments since mid-2008. Though the company has made a substantial effort, it doesn’t yet have plans for a clinical trial. (Click here to read more.) Isis Pharmaceuticals, Inc., of Carlsbad, CA, has also worked about as long and is planning to launch a clinical trial in the next year or two.

It’s still too early to project the costs of treatments that have yet to be tested or even fully designed. Other potential remedies are in trials but at best likely remain years from reaching the market.

Furthermore, an HD treatment regimen will likely involve a cocktail of remedies, meaning that patients – via their insurers – will probably have to pay for more than one drug.

Vertex vice president of research Paul Negulescu (left), Gene Veritas (aka Kenneth P. Serbin), and Vertex vice president of biology Beth Hoffman at the company's San Diego facility, September 2010 (photo by Heather Farr, Vertex)

Patient assistance programs

The HD community must remain vigilant regarding the cost of potential treatments. However, failing to consider a number of factors, the coverage of the Kalydeco costs was perhaps too pessimistic about the future.

First, as I commented regarding the impatience with California’s stem cell institute after ten years of operation without a drug, biomedical research is slow by nature. And it’s expensive, with the average cost of developing a new drug in the U.S. at $1.2 billion. Only one in ten clinical trials results in a marketable drug, although the research from the unsuccessful projects provides highly valuable information on what does not work.

In the case of CF, Vertex is at work on another treatment that would reach thousands more patients with different kinds of mutations.

As Nocera himself noted, Vertex provides Kalydeco for free to patients without insurance.

Lundbeck, the pharmaceutical firm that markets Xenazine, which diminishes some of the involuntary movements caused by HD (chorea), provides financial assistance to patients who qualify. Depending on the dosage, the annual wholesale cost of this treatment can reach $50,000 or more, but, according to the Lundbeck website, “85 percent of U.S. patients taking Xenazine have a monthly co-pay of $50 or less before requesting co-pay assistance.”

It’s highly conceivable that the developers of future HD treatments will provide similar kinds of assistance – especially because these firms will have relied on the good will and extensive cooperation of HD families who participate in research studies and clinical trials. However, it’s not clear what the drug companies will charge insurers.

CHDI and pharma giants

After the founding in 2003 of the CHDI Foundation, Inc., a non-profit virtual biotech firm backed by wealthy donors who wish to remain anonymous, pharmaceutical firms small and large started to gain interest in developing Huntington’s treatments.

As a result, the network of firms working on HD now includes pharmaceutical giants such as Pfizer, Roche, and Medtronic.

As a non-profit with the sole purpose of finding HD treatments, CHDI promotes research on Huntington’s and the diffusion of scientific knowledge about the disease. With more researchers and firms involved, the chances for treatments have grown. Having more options could very well mean that treatments would cost less.

By pouring hundreds of millions of dollars into HD drug research, CHDI has created an incentive to produce cheaper drugs.

As it states on its website, CHDI seeks to connect academic research, drug discovery, and clinical development in order to avoid “costly delays to therapeutic development” and make potential treatments a “good investment” that will result in “full clinical development, including licensure and marketing to get drugs to HD patients.”

Similarly, the Hereditary Disease Foundation and the Huntington’s Disease Society of America (HDSA) have supported research that could yield yet additional drugs.

Patient-driven medicine

Thanks to this level of support for HD research, the HD community stands in perhaps a better position than those facing even more rare diseases.

Nevertheless, orphan disease communities in general have reason to feel optimistic about both the development of treatments and their cost, if the vision of one key medical leader becomes reality.

Lee Hood, M.D., Ph.D., one of the scientific giants behind the Genome Project and the recipient in 1987 of the Lasker Basic Medical Research Award (the American equivalent of the Nobel Prize), has developed a plan for more effective and affordable medicine. In 2000, Dr. Hood founded the Institute for Systems Biology (ISB). Located in Seattle, the non-profit ISB teams scientists and technologists from many disciplines to pioneer the future of research in biology, biotechnology, medicine, environmental science, and science education.

In a 2012 speech at the Seventh Annual HD Therapeutics Conference, sponsored by CHDI, Dr. Hood outlined the importance of systems biology – what I think of as the “big picture” of disease – for HD research. Dr. Hood also advocated for the adoption of P4 medicine: predictive, preventive, personalized, and participatory. (Click here to read more.)

“Patients and consumers will be a major driver in the realization of P4 medicine through their participation in medically oriented social networks directed at improving their own healthcare,” Dr. Hood and Mauricio Flores, J.D., wrote in the March 2012 issue of the journal New Biotechnology.

ISB and several collaborating organizations have run some pilot programs in P4. If it is implemented on a wide scale, Dr. Hood predicts that it will revolutionize our healthcare system. Everybody will carry a health-monitoring device, and diseases will be predicted and prevented long before onset as the result of tiny blood samples taken from a pin prick, the article states.

Predicting falling medical costs

Significantly, costs could plummet.

“P4 medicine will require that all healthcare companies rewrite their business plans in the next 10 years or so,” Dr. Hood and Flores wrote. “Many will not be able to do so and will become ‘industrial dinosaurs.’ There will be enormous economic opportunities for the emergence of new companies tailored to the needs and opportunities of P4 medicine.”

The authors projected that savings will result from a series of factors, including earlier and more effective diagnosis of disease; better matching of drugs with diseases and their subtypes; better identification of genetically based adverse reactions to drugs; the ability to “re-engineer” disease-affected biological networks within people in order to reduce the cost of drug development; an increasing ability to deal effectively with cancer; the use of stem cells for replacement therapy and diagnostics; the routine extension of effective mental and physical health into people’s 80s and 90s; an improved understanding of microbes in the body; a deeper understanding of neurodegeneration (the cause of HD, Alzheimer’s, Parkinson’s, and other disorders); and the digitalization of medical and genetic information.

“On another tact, our prediction is that there will be a ‘wellness industry’ that will emerge over the next 10-15 years that will in time far exceed the size of the healthcare industry,” Dr. Hood and Flores affirmed. “P4 medicine is an area replete with economic opportunities.”

Dr. Hood and Flores believe that P4 medicine will “democratize” healthcare.

“The patient (consumer), through social networks, will drive the emergence of P4 medicine,” they wrote. “Because of intrinsic conservatism and sclerotic bureaucratic systems, physicians, healthcare specialists and the healthcare industry will take a back seat to the power of patient-driven social networks in bringing change to the healthcare system. Indeed, patients may be the only driving force capable of truly changing our contemporary healthcare system to the proactive P4 mode.”

This scenario serves as a serious alternative to the dim view that orphan disease communities will remain relegated to high-cost solutions.

Guaranteeing proper care standards

Indeed, a “revolution” has occurred over the past two decades in how patients have related to their doctors and the pharmaceutical industry (click here to read more).

Nowadays, people enter the healthcare system as both patients and advocates for their well-being.

This outlook led the Arkansas patients to sue for the right to have their Kalydeco costs covered.

Their lawsuit offers a striking similarity with the HD community’s pressure on the Social Security Administration and Congress to update the decades-old, inaccurate government criteria for determining disability benefits for Huntington’s patients (click here to read more). The Arkansas plaintiffs in effect have demanded that the state recognize Kalydeco as the standard treatment for their type of CF.

Negotiating the price

The competition of the marketplace, greater efficiency in drug development, and the revolution in medicine outlined by Dr. Hood should put downward pressure on the cost of drugs.

Patient advocates must play a crucial role in this process.

As the late San Diego biotech leader Duane Roth had told me during a dinner with California stem cell leaders in 2008, patient advocates must find ways to appeal to pharmaceutical companies’ primary interest in profits. Advocates need to lobby and court these business leaders.

At the same time, disease organizations such as HDSA and its network of advocates can pressure pharmaceutical companies and government agencies to assure new drugs’ accessibility and affordability.

In some circumstances, government can join in the process of persuasion and even play hardball, as the Brazilian Ministry of Health did in the 1990s in order to convince multinational pharmaceutical firms to dramatically reduce the price of HIV/AIDS medications. The Brazilian government provides HIV/AIDS drugs for free.

“Local production of generics, the possibility of breaking patents, and the offer of technology transfer became instruments for price negotiations with other countries and the pharmaceutical industry, leading to a real reduction in prices on the Brazilian and international markets,” wrote the coordinator of the country’s National STD/AIDS Program.

The marketplace exists, but it is susceptible to politics.

The rhetoric about the $300,000 drug can scare a lot of people. But in the long run, such a cost is not a foregone conclusion.

The faceless faces of Huntington's disease

Huntington’s disease is an orphan disease with an estimated 30,000 patients and 250,000 individuals at risk for inheriting the genetic defect that causes the disorder. HD is largely unknown to the populace, or even within the medical community. When people do learn about HD, they are shocked by the way this genetic brain disorder robs its victims of their humanity, leaving them twitching nervously, emaciated, and unable to walk, talk, and eat. The result is a slow and ugly death.

For these and many other reasons, HD families face a terrible stigma.

As a pre-symptomatic, gene-positive individual who has just recently begun exiting the “HD closet” (click here to read more), I can attest to the great discrimination, ignorance, and denial that we regularly encounter. Still, I can’t reveal many of the stories, because of the risk of damaging people’s livelihoods.

We hide. We change our names. We cut ourselves off from family and friends.

We live in constant fear.

In the words of HD patient James Valvano, we are “the faceless faces of Huntington’s disease.”

Time for an HD coming-out ritual

The HD community must unite and speak with a common voice to the world: we will be heard, and we will no longer tolerate discrimination.

We will erase forever the stigma of Huntington’s disease. And, by joining hands with the millions of other brothers and sisters victimized by other neurological conditions, end their stigma, too.

As so many other disease communities have done, we must create a ritual for speaking out in public so that people can instantly identify with our plight, our cause for treatments and a cure, and our connection to the chain of social justice and human solidarity.

The Valvano family’s fight

James has thought hard about these issues.

In 2009, James’ 47-year-old brother John was diagnosed with HD after experiencing symptoms first thought to be Parkinson’s and/or the results of a stroke. Soon thereafter, James, who turns 40 this July, also tested positive for HD. He now had an explanation for his own health problems, which stretched back at least five years: shaking legs and occasional twitching in his right arm.

James Valvano (photo from his Facebook page)

“At the time I was not in the best of health and decided to change my eating habits and exercise, alongside a medication regimen,” James wrote me. “I lost upwards of 60 pounds and learned to focus my energy and meditate. I can no longer drive (my eyes flutter/move abnormally), and I sometimes have a hard time with my speech.

“I had to forfeit my small business (Marine Aquarium Shop), so I am home working on advocacy most of the day....

“Since I learned meditation techniques and decided to live more positively, I am able to function a bit less symptomatic….

“Just recently, my niece in Denver was diagnosed with HD (27) and my Dad (79) here in Saint Cloud (Florida). There are seven total (brothers and sisters) at risk. I am the second youngest of the seven, with thirteen nieces and nephews at risk.”

A film about the ‘monster’

James might have devised a successful formula for a neurological coming-out ritual.

As part of his growing advocacy, James decided to produce an allegorical film depicting HD symptoms and the fear felt by its victims. He titled it The Faceless Faces of Huntington’s Disease.

In the film’s captions. James calls Huntington’s disease a “monster” and a “living nightmare.” The main character wears a black, hooded robe and a silver, ominously expressionless mask. Afflicted by HD, this person lives a lonely life as symptoms intensify.

Police officers, also wearing masks, lock up the HD person in a small cubicle. The HD person then visits a cemetery.

“Without a cure, Huntington’s disease will win,” the film’s captioning continues. “We are not monsters.”

At the very end, James appears onscreen: “My name is James Valvano. I have Huntington’s disease. I am no longer a faceless face.”

You can watch the film below.




Scare tactics?

The Faceless Faces is not an easy film to watch. I believe it will especially shock people who have not heard of HD before or ever seen an HD patient.

In fact, the film has generated controversy among some members of the HD community. One viewer accused James of using “scare tactics.”

James addressed that criticism in a comment in an HD discussion group on Facebook.

“Let me say that I searched high and low prior to creating the film, for another interpretation similar to mine – to no avail,” James wrote in the February discussion. “Did I have another format? Yes. Why did I change the portrayal to its current state? I believed that HD needed to be exposed for exactly what it is – what I experience on a daily basis – what thousands experience (whether they have HD, [are] not yet sure, or if they are a caregiver).

“At the end of the film, it was key (in my expression) to ‘transform’ the ‘monster’ into human form – the person who lives with this horrific disease, the thousands of wonderful and loving people in our community who are not given the level of awareness which is so desperately needed.”

I contributed to the discussion with my own comment on the film:

“Someone once criticized me for saying HD was ‘dehumanizing.’ I did not apologize for my description, because it IS dehumanizing. The individual thought I was calling HD people unhuman. But it's not the people – it's the disease.

“And that is James' point. HD is a shocking disease. And unknown. So it's difficult to explain.

“I thought James packed in a lot of info into a very short time. Yes, many people will find it shocking. We need different approaches for different audiences. Some people find it difficult to look at HD people. I found it difficult to look at my own mom, because the disease had stolen her humanity and because I was looking at my own future.”

The Neuro Film Festival

The Faceless Faces has also created a stir in the community of neurologists.

James entered the film in the 2011 Neuro Film Festival, sponsored by the American Academy of Neurology Foundation. Among the more than 100 entries, it received the third highest number votes from the online viewing public. (A film about multiple sclerosis came in first, followed by one about arachnoid cysts.)

According to the festival’s website, the goal is to “help raise awareness through video about brain disorders and the need to support research into preventions, treatments and cures.”

The official first- and second-place winners of the competition, judged by a panel of academy members and film experts, will be announced at the festival in Honolulu on April 10.

‘I am No Longer Faceless’

To build awareness even further, James is preparing part two of the film, titled The Faces of Huntington’s Disease: I am No Longer a Faceless Face.

For this phase of the project, James is collecting short video clips of people taking off a mask and stating this sentence: “My name is (state name) and (I have Huntington’s disease) (someone I love has Huntington’s disease) (I am at risk for Huntington’s disease), etc., and I am no longer a faceless face.”

In a teaser clip for part two, James calls for everybody in the HD community tell his or her story: “You are special. You are a fighter. Our story must be told. Let’s put the stigma to rest. The mask is off. We are no longer faceless. It’s a new day for awareness. We will let the world know – together.”

James plans to travel across America to visit participants in the film. He also hopes to fly overseas

“I believe it is time for us to unite as a worldwide community and bring about a wave of awareness unlike any other!” James wrote on his website.

Combating discrimination

The task of ending the facelessness of Huntington’s disease is urgent. Despite the passage of the Genetic Information Nondiscrimination Act of 2008, people in the HD must still confront harsh discrimination and ignorance about the condition. (In a future article I plan to explore the enforcement of this act.)

HD people continue to land in jail because police officers think they are drunk or because of aggressive behavior caused by the disease.

Amanda K. Titus-Meadows of Marquette, MI, recently told me and others in an HD group on Facebook that her mother Teresa, a licensed practical nurse, was laid off from her job at a hospital late last year because she’d been diagnosed with early-stage Huntington’s. Amanda gave me permission to tell this story.

Suffering mainly from short-term memory loss, Teresa, 50, was nevertheless told “by both of her doctors, her neurologist, and her memory specialist that she is perfectly capable of still working. They were the ones who encouraged her to speak to a lawyer, because they believe that her rights have been violated and her employer is breaking the law.”

The doctors also pointed out that the hospital had asked for Teresa’s “medical records without a release.” Amanda added that Teresa’s boss filed disability and unemployment papers without Teresa’s consent.

The family has retained an attorney.

Sickening treatment

In the discussion, other HD-affected people revealed that co-workers harassed them or pushed them out of their jobs.

“I'm sickened that things like this happen to people,” Amanda wrote. “How upsetting that we be counted out just for carrying a disease. This should be handled with kid gloves and no different than a case with somebody who has diabetes, lupus, or any other disability.

“I hope that for the future of our potentially afflicted children that we are able to make the disease clear to those who don’t understand and protect them from suffering the same discrimination.”

I added my own feelings about this situation: “I am deeply saddened, disturbed, and angered.… NOW WE KNOW why so many people in the HD community are FACELESS! We've all got to fight for our rights! Many people have asked why I use a pseudonym on my blog. It's experiences like Amanda's mom's that have kept me anonymous for fear of losing my own job.”

Removing the mask (again)

To those in the HD community who would still hesitate to end their facelessness, James says: “If not now, when?”

After remaining anonymous for 15 years after my mother’s diagnosis with HD in 1995 (she died in 2006), I began to exit the HD closet last year.

On February 7 of this year I came out to some 250 prominent HD scientists and other attendees by giving the keynote address to “Super Bowl” of Huntington’s disease research, the 6th Annual HD Therapeutics Conference, held in Palm Springs, CA, and sponsored by the CHDI Foundation, Inc., the so-called “cure Huntington’s disease initiative.”

My speech was titled “Blog Entry No. 85 … Unmasking the World of Gene Veritas: An Activist Copes with the Threat of Huntington’s Disease.”

On March 31, I spoke about HD to the very first time to a trusted co-worker, although I’m still deeply fearful of potential discrimination if more colleagues find out.

Like tens of thousands of affected, gene-positive, and at-risk individuals, I’m in a race against time. We are all awaiting treatments for HD.

For me, the time to speak out is truly now. I will submit my own short video clip for inclusion in The Faces of Huntington’s Disease: I am No Longer a Faceless Face. Please watch below.

This video is my way of bidding farewell until my next article – and of asking everybody to help make HD, and other devastating neurological disorders, diseases with real faces.

Gene Veritas: No Longer a Faceless Face of Huntington's Disease from Gene Veritas on Vimeo.

A cascade of emotions about Huntington’s disease

The world will remember Friday, March 11, 2011, as the day that a devastating earthquake and tsunami overwhelmed Japan and triggered a potential nuclear disaster in a land already scarred by the bombs of Hiroshima and Nagasaki.

I also will remember that day for some very personal reasons: a cascade of difficult feelings about Huntington’s disease nearly overwhelmed me.

My heart goes out to the people of Japan. More than ever, the world needs to show solidarity with the victims of natural and manmade disasters.

I’m also reminded of the need for solidarity with people affected by HD and so many other similar diseases – like an acquaintance, the mother of three, struck down in her prime by multiple sclerosis.

Memories of testing

My own series of difficult feelings began the evening of Sunday, March 6, when I checked one of the HD groups on Facebook and read about a young man in the armed forces who was getting tested for the disease. The young man’s father has HD, and his mother was seeking advice from the group.

The military doctor knew nothing about HD. The clinic drew the serviceman’s blood and sent it to a commercial testing service. The serviceman received none of the pre-test genetic counseling that is mandatory at clinics that follow accepted standards for genetic testing.

The young man’s situation triggered a flood of memories of my own genetic test for HD in 1999. My wife and I received counseling prior to obtaining my result, and, as my support person, my wife was required to be at my side at the moment the doctor revealed the result. The counselor was also present on that day.

I tested positive. My wife and I left the medical office in a daze. As I backed our car out of the space in the parking garage, I swung too far to the right and scraped the right front fender on a column (click here to read more).

I felt deep anger, frustration, and resignation. Now I knew that I would share the HD fate of my mother, who already had full-blown HD and had lost most of her ability to speak and care for herself. She ultimately died of HD in 2006.

Desperately wanting to help

I desperately wanted to help the young serviceman obtain support.

I wrote to the Facebook HD group:

“He should NOT just test instantly like that! There is a protocol that requires counseling from a genetic counselor and a psychologist. … Testing is a huge event in a person's life – whether the result is negative or positive. A counselor or psychological support person should be there when he gets the results, and also a friend, spouse, or other family member.... Also, it's important to remember: a positive test result for HD is NOT a diagnosis for HD. The person can live years or even decades without symptoms.”

I frantically began to work my contacts in the local community to see if we could arrange for a genetic counselor or other professional support person to assist him on the day of his test results.

Driving home our message

Before I got too far, though, his mother notified the group: he tested negative!

What a relief! I thought.

But, also, what a close call! I wondered: how would he have reacted had he tested positive?

This young man’s story once again underscored the message that I and other HD activists must drive home.

Sadly, HD remains a largely unknown disease, even within the medical community. As a society we need to build greater awareness about orphan diseases, provide up-to-date information on the procedures and implications of genetic testing, and be on the lookout for potential genetic discrimination.

Sharing my story (again)

As other HD community members and I attempted to assist the serviceman and his family, I braced myself for another stage in my transition to a public advocate for HD.

On February 7, I gave a public speech to some 250 people at the annual “Super Bowl” of Huntington’s research, the 6th Annual HD Therapeutics Conference, held in Palm Springs, California, and sponsored by the CHDI Foundation, Inc., informally known as the “cure Huntington’s disease initiative.” And on February 28 I came out about my gene-positive status in a talk to the local support group in San Diego.

A couple days later, I read that a former college classmate, now a prominent philanthropist and documentary filmmaker, would be in town on March 8 to give a presentation.

We hadn’t seen each other since graduation from Yale in May 1982, but I decided to attend her event as a show of support for her work in social justice and women’s rights.

Before the event, I wrote her a personal letter thanking her for her social commitment.

“I wanted to share with you my own odyssey of the past 16 years advocating against genetic discrimination and raising awareness about the need to find treatments for Huntington’s disease (HD) and other orphan diseases and neurological disorders,” I wrote. “I believe all areas of social justice are interconnected.… So I believe we share common ground.”

Before she gave her speech, my classmate greeted me warmly. We hugged, and she asked me about what I had been up to since graduation. I told her of my deep involvement with Brazil as a professor of history.

Afterwards, I went to congratulate her. I gave her an envelope with my letter – and a copy of my CHDI speech, “Blog Entry No. 85 … Unmasking the World of Gene Veritas: An Activist Copes with the Threat of Huntington’s Disease.”

Struggling with doubts

My old classmate is extremely busy, so I don’t know yet whether she read the letter or watched my speech.

But, as I said in an e-mail to some friends, the reconnection with my classmate was “very emotional.”

Just seeing a classmate for the first time in nearly three decades was enough emotion for one day.

But, on top of that, came my HD activism – my life’s work, my life itself, so deeply affected by my mother’s demise and my inheriting the defective gene from her.

I struggled with doubts in the days leading up to her event: should I “bother” her by coming out about something so sad and complex as Huntington’s disease and its terrible impact on families? Isn’t it presumptuous of me to give her a letter and my DVD after so many years of no contact? Will she be interested in the cause in any way?

“Maybe she’ll make a film about HD,” a friend and HD activist suggested hopefully.

“I didn’t ask for anything in the letter,” I replied. “I am doing my job as an advocate: getting the word out about HD. I will just be happy if there is just one more person praying for us.”

Testing the waters in the workplace

On Thursday, March 10, I started exploring a huge and inevitable step: coming out about my HD status in the workplace, potentially the most explosive arena of my life in terms of genetic discrimination.

During lunch with a trusted co-worker, I mentioned that I was living an extremely intense period of my life outside of work.

This was the very first time that I alluded to my activism after erecting an absolute firewall between my HD life and my professional life following my mother’s diagnosis in 1995. I have kept that firewall intact because of fear of genetic discrimination.

The disintegrating firewall

I didn’t mention the word “disease” to my co-worker, but I did explain that I am involved with a cause and a situation that could ultimately impact my situation in the workplace. I revealed to her that I had given a speech and that I would like to give her a copy of it sometime. I asked her to keep my situation confidential for now.

My stomach felt as if it were turning upside down, and my mind wanted to go blank. I was having a difficult time finding the right words.

I felt the firewall between my job and my activism being disintegrated by my words and the violent currents of my fears about a future with Huntington’s disease. As if to act out this huge change in my life, I moved my arms back and forth next to each other along the table. This gesture represented my dual life – my job and my HD activism moving in parallel and never intersecting.

My co-worker sensed my difficulties and reassured me by saying that I should tell my story on my own terms and on my own schedule.

Indeed, as I told her, I still haven’t worked out for myself how to proceed on the professional front.

Planning a trip to Alnylam

More than a month has passed since my CHDI speech. I’m living as intensely as ever as I step further and further out of the HD closet.

I turned 51 last December, and as I progress into this decade of my life, I will get closer to the inevitable onset of the HD symptoms that destroyed my mother’s mind and her ability to walk and eat.

But there has never been a time of greater hope in the quest of scientists to find treatments and a cure for HD.

In the midst of my personal churn of emotions last week I firmed up plans to visit Alnylam Pharmaceuticals in May to give a talk on HD and observe the companies’ researchers at work on a potentially revolutionary treatment using RNA interference to stop the disease at its genetic roots.

A break from the real battles

Luckily, I began a week’s vacation on March 11.

That also happened to be the opening day for the film Battle: Los Angeles, about an invasion of aliens seeking to colonize Earth for its water resources.

After school I picked up my daughter – our 10-year-old “miracle baby,” who tested negative in the womb for HD.

As the first act of her weekend and my vacation, we headed for the movie theatre.

Life’s major battles continued – in the stark reality of both the Japanese tsunami and the search for treatments and cures for HD and other life-sapping neurological conditions.

And also in the fantasies of Hollywood, where, for at least a couple hours, I could find a bit of escape and catharsis.