As he lay dying: FDA and Huntington’s disease families meet to ponder potential treatments

On Tuesday, September 22, when the U.S. Food and Drug Administration (FDA) focuses on Huntington’s disease drug development at a meeting with affected individuals and advocates, HD families must drive home the sorrowful truth: people are dying because of the lack of effective treatments.

About two weeks ago, shortly after pouring out my heart about my family’s HD struggles on the FDA’s pre-meeting questionnaire, I received a message from the mother of 18-year-old Terry Leach of San Diego: “It’s Terry’s final days if you wanted to say good-bye.”

A couple days later, on Labor Day, I visited Terry, who suffers from juvenile HD, in his bedroom. As Terry slept, his mother Angela and I looked on. Next to us a home healthcare worker prepared a can of liquid food to be administered via a feeding tube attached to Terry’s abdomen. Hospice workers are also helping.

“He grew a lot,” I said to Angela, amazed at how, despite the particularly cruel toll of juvenile HD, his body had strived to develop. It had been more than a year since I had last seen Terry.

“Yes, he did,” Angela said.

I noticed Terry’s beard and his healthy head of somewhat wiry, dark brown hair.

“You have a very handsome son,” I continued.

“Thank you,” Angela said.

Terry Leach resting at home (family photo)

Unspeakable pain

As Angela nervously shifted her balance from foot to foot, I sensed that she continued to carry the unspeakable burden that comes with juvenile HD: Terry’s first symptoms as an infant, his need for a full-time aide in school after losing his ability to walk and talk, the insertion of the feeding tube in 2010, Botox injections into his arms and legs in recent years to relieve pain, and leg and foot operations, among other procedures and hospitalizations.

Although Terry still attended school last academic year and also the summer session, he has declined considerably in the last few months, Angela said.

The night before my visit, he vomited after receiving liquid food through his tube. On the day I visited, the aide would give him only one can instead of the usual two, noting that his body would not accept anything more than that very small amount.

I asked Angela if I could touch Terry.

“Sure,” she said softly.

I ran my hand along the top of his hair. I remembered Angela and her family’s steadfastness in caring for Terry. I also recalled fondly our collaboration in the cause, starting with an article I wrote about them in 2009. In 2012, Terry emerged as “SuperTerry” in an artist’s comic-book like rendition as a hero defeating HD. In 2014, our families participated in the 2014 Team Hope Walk of the San Diego Chapter of the Huntington’s Disease Society of America.

SuperTerry in San Diego artist Lee Ellingson's rendition (above) and with Gene Veritas (aka Kenneth P. Serbin) at the 2014 Team Hope Walk (below, photo by Misty Oto)

Seeking feedback from the community

As Terry lies dying, the September 22 FDA event, a public meeting on “patient-focused drug development,” will seek feedback from affected individuals and others in the HD community.

The meeting will occur from 9 a.m.-12:30 p.m. at the FDA’s White Oak Campus in Silver Spring, MD. Pre-registration for attending the meeting and viewing via webcast is closed, but the FDA will make available a video of the proceedings shortly thereafter.

The meeting stems from the reauthorization of the Prescription Drug User Fee Act in 2012, in which Congress required the FDA to more systematically solicit input from patient communities with regard to drug development. The FDA hopes this will help its review process.

Huntington’s disease became one of just 20 diseases selected by the FDA for a patient-focused meeting through the end of 2015.

‘Nothing for neurological disorders’

Responding to the preparatory questionnaire, I revealed my situation as a carrier of the HD genetic defect and my mother’s decline and death from HD in 2006.

“I fear that I will become like my mother,” I wrote. “She had mild chorea [involuntary movements associated with HD]. I would not mind having chorea as long as I can continue to be myself, work, and not become a burden on my wife and daughter. My mother became a shadow of herself. I have great anxiety about losing my personality and ability to work as a college professor and writer.”

Like others, I would like to see a treatment that prevented symptoms, I added.

“If I get symptoms, then I would like a medication that allows me to manage the disease just as other diseases such as diabetes are managed without affecting a person’s livelihood, family life, or activities in general,” I continued. “There are lots of advances in cancer treatments, for instance, but really nothing in the field of neurological disorders that prevents, halts, or reverses the condition.”

I uploaded my response to the FDA’s public docket regarding the meeting. Anybody can comment at that link through November 23, 2015.

Speeding up clinical trials

At the meeting, I also plan to urge FDA officials to allow researchers and clinical trial administrators to use new technologies to measure the effect of medicines.

All clinical trials of new drugs taking place in the U.S. must receive the approval of the FDA, considered to have the world’s most rigorous standards. Although the drug industry executives I have met recognize the importance of that rigor in assuring the manufacture of safe and effective drugs, they sometimes have also expressed the need for the FDA to be more flexible and allow for faster clinical trials.

Generally, the FDA still does not accept techniques such as brain scans. HD researchers and other scientists are vigorously searching for biomarkers – signs of disease and drug effectiveness – in the blood, cerebrospinal fluid, and other materials taken from the body that can be measured using the scans and other new techniques.

Instead of waiting for a doctor’s clinical observation of an improvement, these techniques could potentially allow faster and earlier reading of a drug’s effectiveness.

I will stress that the FDA work closely with scientists and the HD community to make clinical trials as efficient and meaningful as possible.

Speed is of the essence for the HD community.

Heartbroken by another loss

As of this writing, Terry is stable, but his prognosis is not positive.

To give me strength as I travel to Maryland on September 21 and take part in the meeting the next day, I will keep fresh my memory of Terry.

I am heartbroken by yet another loss to HD.

As an advocate, I feel I have failed to fulfill the promise of hope presented so often to families such as the Leaches. No 18-year-old should die.

I am comforted to know that Terry is in loving hands – and that he never gave up, always smiling that infectious smile. And I am committed to making sure policymakers know of the people whose lives they could improve and save.

Terry in 2010 as a Hero of the Carlsbad Marathon

New film unmasks the raw reality of Huntington’s disease

A new, award-winning documentary film, The Huntington’s Disease Project: Removing the Mask, reveals the raw reality of HD so thoroughly and authentically that it should become required viewing for health care professionals and trainees in the neurological field.

This 100-minute film, not yet released widely, is also a must-see for the HD community and the general public, although it will likely cause many to recoil from what it calls the “monster” tormenting HD-affected individuals and their families.

As an HD gene carrier and long-time grassroots advocate who saw his mother succumb to the disease, I consider myself a hardened observer.

Even so, Removing the Mask shocked me with its exploration of the lives of HD-affected individuals and caregivers, including producer and narrator James Torrington Valvano, diagnosed with HD in 2009 yet still able to function sufficiently to make the film.

With an anthropologist’s eye, James probes the many layers of HD reality – and the hearts of its victims.

Removing the Mask delves into the wide range of issues HD families face, including medical challenges and social disruption.

The HD community will recognize many of them, although they are rarely discussed so openly in a medium such as film: ignorance about the disease, misdiagnosis, denial, family tensions, rage and aggression, genetic testing, financial devastation, caregiving, and loss of the affected individual’s independence, to name just a few.

Removing the Mask does not shy away from the most difficult themes: inaccurate racial interpretations of HD by physicians, associated sexual disorders, suicide, the exclusion from clinical trials of HD people with suicidal tendencies, and mercy killing. It also pays close attention to juvenile HD, often omitted in the overall conversation about HD.

In striving for a comprehensive view of HD, Removing the Mask adamantly advocates for a broad understanding of the disease by medical and psychiatric professionals, relevant government agencies, and the public. This includes recognition of HD as not just a movement disorder, but also one involving cognitive, emotional, and behavioral difficulties.

Although Removing the Mask mirrors the detailed information about HD known to specialists, many non-specialist health professionals don’t understand the disease.

Removing the Mask is not a textbook-like film but a genuine illustration of the disease. Rather than a medical or scientific authority explaining HD for us, in the film we feel the pain as the affected and their loved ones tell us what it's really like to have the disease.

James brings it all to life with testimonies that are brutally honest.

You can watch the Removing the Mask trailer in the video below.

Shaving seven hours a day

At James’s invitation, I recently watched the film by myself in a private online session on my home computer.

One of many poignant segments concerns John and Sue Wright of Kent, England. John, who liked to work with computers before he fell ill, was diagnosed with HD in 1992, and soon thereafter Sue became his caregiver. In the film, she describes his mental decline.

“He was waking every morning threatening to kill me and throw me out the window,” Sue recalls. “He was sharpening knives in the kitchen constantly, and he was assaulting me. I always reported the assaults, for my own safety, to the police, but never wanted him prosecuted. I knew it was the disease making him behave this way, and not his intention.”

To avoid harm, Sue moved out, although she returned home up to seven times each day to care for John.

John developed a condition experienced by a number of HD-affected individuals: obsessive-compulsive disorder (OCD).

“He was obsessed with any paper towels, tissues, etc.,” Sue remembers. “He would pile them up and keep them. If I attempted to throw them away, he would retrieve them from the rubbish bin and put them back in their piles.

“He was also obsessed that any facial hair would suffocate him. So he started shaving for up to seven hours a day, making his face red raw.”

Starving himself to death

Sue had to have John legally committed to a mental health facility.

“This was a horrific experience, as the police were brought into the house in riot gear, and he was dragged out of the house still trying to eat his lunch,” she explains. “My twin Sheila was wonderful. She stepped into the house when [it] happened so that John would blame her rather than me for what happened. This gave her nightmares for quite a considerable period but thankfully did preserve John’s and my relationship.”

Over the next several years, John lost his ability to walk and speak. Eating also became extremely difficult. When asked if he wanted a feeding tube, Sue says in the film, John violently shook his head no.

“John indicated that he’d had enough when he started refusing to eat and drink,” she says. “His quality of life was non-existent, and I knew he wanted it to be over.”

Mercy killing is illegal in the United Kingdom. “My only option was to help him as he starved himself to death,” Sue says plaintively.

John died in 2006. He was 56.

‘We have a face’

At the film’s outset, James declares that the HD monster “caused so many people across the world to hide behind masks, masks of silence.[…] It was time to destroy the monster. Our goal was very simple: to remove the mask of Huntington’s disease.”

He adds: “It was time to show the world that we have a face.”

A former mental health care professional and small business owner forced to quit after his diagnosis, James began work on the film in 2011, with a powerful short showing people taking off masks and saying “I am no longer a faceless face” (click here to read more).

Before the short, he had never made a film, although he had studied communications, film, and psychology at St. John’s University in Jamaica, NY, for a while in the early 1990s.

James decided a film was the best way to get out the word about the disease.

“It frustrated me and so many people that no one was telling or showing the real truth behind he disease,” he said. “Advocacy is more than walking, fundraising, wine-tasting, and dinners. All of those ways to advocate are important, but they alone were not working. How can we expect the world to know about HD if we are not willing to get outside the box?”

In addition to his work as an advocate, James cares at home for his older brother John, now in the advanced stages of HD, with the assistance of his spouse, Ian V. Torrington. James’s father died of HD and cancer. Five other siblings and numerous other relatives are at risk for HD. Ian also cares for James.

Ian V. Torrington (left) and James Torrington Valvano (personal photo)

To support the project but also to network globally to raise the profile of HD, James and other advocates from HD families formed WeHaveAFace.org.

Recently granted nonprofit status, the organization provides online and mobile support to the HD community. Activities include fundraising for HD research and family assistance, online support groups, the production of a quick reference guide about HD for police and rescue workers, and a mobile application with ample information about HD.

A number of WeHaveAFace.org’s U.S-based regional advocates tell of their struggles with HD in Removing the Mask.

According to James, he spent less than $7,000 on the film, with funds coming from a t-shirt campaign, other small donations, and “heavy hitting on my credit cards.”

‘We need the world to watch’

According to my conversations with James via Facebook, he and his film team held “dozens upon dozens” of Skype calls and exchanged thousands of e-mails in the background research for the Removing the Mask.

Not everybody agreed with James’ direct approach. According to him, one advocate broke off from the project “because I was tackling suicide.”

James himself admitted experiencing powerful emotions during the project.

“Filming the topic of suicide was one of the most difficult and painful experiences in my life,” he wrote in a digital journal kept during the production. “As a filmmaker you want to get the rawness of the topic, but as a person with Huntington's disease, my heart and soul ached through every second.”

In the film Cindy Dupree, an HD-stricken woman from Alva, Oklahoma, and her husband Ron speak hauntingly about suicide.

“I am not ashamed or afraid to talk openly about suicide, because it affects so many people within the Huntington’s community,” says Cindy.

“I know that she battles thoughts of suicide each day, and I fear that I will receive that call that ‘your wife has just taken her life,’” says Ron. “I can only imagine how other caregivers feel. I know they are fighting the same battles we are. I am angry a lot of the time and do my best to realize and understand that it is the disease and not my wife.”

Cindy says that knowing Ron and their three daughters rely on her keeps her “grounded.”

“The documentary was never created for the Huntington's community,” James added. “We had to get outside the box and set our aim on the general public. Although I believe and hope that the film will resonate within our own community, we need the world to watch exactly what we go through.”

How to see the film

WeHaveAFace.org celebrated the official launching of Removing the Mask on June 20 in James’s hometown of St. Cloud, FL. He has entered it in about a dozen film festivals in the U.S. and abroad.

It won in the category of best feature documentary in the July 2015 monthly competition of the Miami Independent Film Festival.

James hopes to make the film available to the general public in early 2016 via DVD, Blu-ray, and Vimeo.com. He is also hoping to include it on Netflix and iTunes.

For now, organizations and support groups interested in showing the film as part of an HD awareness-building or fundraising event can do so by registering at this link.

The dilemma of illness

The Huntington’s Disease Project: Removing the Mask joins a group of high-quality documentaries about HD launched in recent years, including The Lion’s Mouth Opens, a courageous HBO film about filmmaker-actress Marianna Palka’s decision to test for the genetic defect.

With its unapologetic presentation of HD, Removing the Mask will stir controversy not just about Huntington’s, but also the way in which people and institutions deal with the terrible challenges of neurological disorders in general.

After watching the film, I kept remembering the dilemma I faced six years ago when I was directing the construction of an independent website for the Huntington’s Disease Society of America’s (HDSA) San Diego chapter, whose board I served on.

Should the homepage use positive, “feel good” images to advance our cause? Or should it show the harsh realities of HD? One of my fellow board members, a public relations specialist not from an HD family, cringed when I showed him some of the photos of gaunt HD-affected individuals I was proposing for the site. I indeed used some of those photos on the site (which is no longer operative).

I don’t know if I did the right thing.

I believe that Removing the Mask faces the same dilemma. It’s raw, but will it ultimately be effective?

I believe that it can be in the health care community. Removing the Mask would make a fine multimedia companion to HDSA’s A Physician’s Guide to the Management of Huntington’s Disease.

Professionals and students in the medical professions must see this film. So must public officials like the administrators at the Social Security Administration and doctors who evaluate HD-affected individuals for disability. And so must general medical practitioners, neurologists, psychiatrists, and others who potentially come into contact with HD patients.

I’m hoping that the Miami festival award indicates that the general public is also ready to help destroy the monster of HD.

(Note: I have a very small part in the film, where I take off my own mask, but otherwise had nothing to do with the content.)

Reinforcing the global fight against Huntington’s disease: a visit to Brazil and a reminder of our common struggles

The global cooperation necessary to defeat Huntington’s disease requires the bridging of cultural divides. It entails recognition of each country’s unique needs and contributions – but also of the common struggles involved.

With this in mind, last month I embarked on another phase of my own international advocacy by traveling to Brazil, the country I have studied since 1986, to deliver a speech on HD and build new connections for the cause.

The world’s fifth most populous country, with over 190 million people, Brazil occupies a significant place on the world’s HD map. Perhaps 19,000-plus Brazilians suffer from the disease, and tens of thousands are at risk.

Thus, once the global HD clinical trial and research study platform known as Enroll-HD gets under way in Brazil, the country’s potential contributions to the search for effective treatments will increase substantially (click here to read more).

A ‘bi-cultural’ perspective

As I have done almost every year over the past three decades, I visited Brazil primarily to work on my ongoing research in Brazilian history. In all, I have spent nearly seven years there. In 1991, during my Ph.D. research in Rio de Janeiro, I met my wife Regina.

Brazil is my second home. I refer to myself as “bi-cultural.”

Even before I joined the board of the San Diego chapter of the Huntington’s Disease Society of America in 1998, I established contact with Brazilian HD activists who founded the Associação Brasil Huntington (ABH) in 1997.

As a carrier of the HD genetic defect, I spoke in 2013 about my personal strategies for avoiding onset of symptoms at the sixth World Congress on Huntington’s Disease, held in Rio (click here and here to read more).

Gene Veritas (aka Kenneth Serbin) at Ipanema beach in Rio de Janeiro (photo by Regina Serbin)

Combating genetic discrimination

During this most recent trip, I advocated for HD-related issues in my meetings with political leaders.

In 2005, the Brazilian Senate passed a bill protecting citizens against genetic discrimination. However, the Câmara dos Deputados (the House of Representatives), has yet to take up the matter. Until then, the bill cannot become law.

Senator Aloysio Nunes Ferreira Filho, who ran for vice president in the 2014 election on the losing ticket of the opposition Brazilian Social Democracy Party, supports the legislation. During my visit to his office in Brasília, the capital, he phoned a colleague in the Câmara to urge action on the bill.

Senator Aloysio Nunes Ferreira Filho (above, photo by Gene Veritas) and Gene Veritas in the chamber of the Senado Federal in Brasília (below, photo by Lucas Souza) 

Defending the rights of the disabled

Later, in São Paulo, South America’s largest industrial and financial hub, I attended a presentation by the famous liberation theologian Leonardo Boff about the geopolitical state of the world, the threat to the global environment, and the current political crisis in Brazil.

The event was moderated by Paulo de Tarso Vannuchi, who served as Minister of the Special Secretariat for Human Rights from 2005-2011 in the government of the ruling Workers’ Party.

Vannuchi briefly introduced me to leaders of the National Council for the Rights of the Disabled. I committed to furnish them with information about HD and put them in touch with the ABH.

Vannuchi told the audience of 60, which included clergy and grassroots social activists, of my HD advocacy and suggested that the reporters present interview me.

Paulo Vannuchi, former Minister of the Special Secretariat for Human Rights (photo by Gene Veritas)

That same day I gave an interview to the TVT television outlet commenting on the importance of Boff’s speech. (You can see the report on the event, including my commentary, by clicking here).

Shortly after my return from Brazil on July 22, one of the reporters present at the event, São Paulo-based radio broadcaster Marilu Cabañas, interviewed me via phone about HD for her program. Shocked to hear of police detentions of HD-affected individuals in both Brazil and the U.S. because of ignorance about the disease, she headlined her report with that fact.

Bioethical challenges

I gave my speech, “Huntington’s Disease, Bioethics, and the Promise of Biotechnology,” on July 20 at the Universidade Candido Mendes (UCAM) in downtown Rio de Janeiro.

I have known the rector, Candido Mendes, for more than 20 years. My friends and colleagues, UCAM Professor Luiz Alberto Gómez de Souza and his wife Lúcia Ribeiro, both leading scholars and grassroots activists of the Catholic Church, organized the event. (Brazil is the world’s largest Catholic country.)

During my hour-long presentation in Portuguese, I recalled my family’s long fight against HD, beginning with my mother’s diagnosis in 1995, followed by positive test for the genetic defect in 1999 and the wrenching experience of testing our daughter Bianca in the womb in early 2000.

I felt deep relief after showing the audience pictures of our HD-free “miracle baby” in action as a youth soccer player. I spoke of the “double luck” we currently savor: Bianca will never face the terrible threat of juvenile HD, and I remain symptom-free despite having long passed my mother’s age of onset.

“At 55, my mother […] could no longer drive, she couldn’t work, she couldn't talk,” I said. “By a huge stroke of luck, I am healthy. Each day is a blessing.”

However, I also pointed to the many other bioethical challenges faced by HD families, including discrimination, family and caregiver stress, financial burden, and the lack of adequate facilities and caregiving personnel for late-stage patients.

The room became very quiet as I related how Carol Carr (of Georgia) in 2002 took a gun to the nursing home where her two HD-stricken sons lay helpless in bed and shot them dead to prevent further suffering. Carr spent nearly two years in prison.

“That was extremely sad for our community,” I recalled. “Huntington’s disease is not something easy to speak about.” 

With no effective treatments, such was the degree of hopelessness that has plagued the HD community, I had pointed out earlier.

The hope of clinical trials

“But I came to Brazil not to speak just about sadness,” I continued. “I also came to speak about hope and the promise of biotechnological research.”

The scenario for the HD community has changing radically in recent years with major advances in research and the advent of clinical trials to test potential remedies, I said.

I spoke of the immense potential revealed in the announcement last year of the gene-silencing clinical trial by Isis Pharmaceuticals, Inc. Citing an e-mail from Isis executive Frank Bennett, Ph.D., received the day before the presentation, I confirmed that the trial would start by year’s end.

(Indeed, the morning after my talk, Isis officially announced that it had commenced the trial.)

You can view my talk in the video below.

A Doença de Huntington, a Bioética e a Promessa da Biotecnologia from Gene Veritas on Vimeo.

A local commitment to the cause

During the Q & A, several Brazilian HD-affected individuals and caregivers spoke of their many struggles with the disease.

They also expressed excitement about the Isis clinical trial.

Carmen Paiva, Ph.D., spoke of her lab’s work in HD genetic and epidemiological research among Brazilian HD families. She told the audience of other local researchers and physicians focusing on the disease.

Recognizing common struggles

At the close of the session, Prof. Gómez de Souza evoked a key point of my presentation: the interconnectedness of neurological disease research and the common struggles of the afflicted.

He spoke with profound emotion about his brother, the renowned actor Paulo José Gómez de Souza, who has suffered from Parkinson’s disease for more than two decades but has successfully strived to continue working.

The struggles are shared among diseases – and among nations.

I look forward to celebrating with my Brazilian relatives and friends the defeat of HD, Parkinson's, and other neurological disorders as a result of a truly global effort.

Isis Pharmaceuticals launches historic clinical trial to silence Huntington’s disease gene

Isis Pharmaceuticals, Inc., based in Carlsbad, CA, has launched its long-awaited clinical trial to test a drug designed to attack Huntington’s disease at its genetic roots.

In a July 21 press release, Isis said it had initiated a Phase I human clinical study of ISIS-HTT_Rx, its compound aimed at diminishing the symptoms of HD. HTT_Rx signifies a medication for HD. The disease is caused by a defect in both the huntingtin gene and protein, which are symbolized by the letters htt.

“ISIS- HTT_RX is the first therapy to enter clinical development that is designed to directly target the cause of the disease by reducing the production of the protein responsible for HD,” the release stated.

In partnership with Roche, the Switzerland-based pharmaceutical giant sharing costs of the typically expensive clinical trial, Isis thus becomes the first entity to use a gene-silencing technique in the attempt to stop HD.

“Although the toxic protein produced from the huntingtin (HTT) gene in HD patients has been a target of interest for many years, no therapies have advanced to clinical trials to treat the underlying cause of the disease,” Frank Bennett, Ph.D., Isis’s senior vice president of research, stated . “Our antisense technology has enabled us to discover and develop ISIS-HTT_Rx, the first therapeutic approach designed to treat the genetic cause of HD."

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

A ‘significant milestone’

HTT_Rx is an antisense oligonucleotide, an artificial strand of DNA created by Isis to block the action of the RNA molecules that translate the huntingtin genetic code to make the huntingtin protein.

Involving about 36 early-stage HD patients at about six sites in Europe and Canada, the Phase I trial focuses on the safety and tolerability of HTT_Rx. According to an Isis spokesperson, the sites will start recruiting participants as early as in a few weeks.

Depending on the pace of recruitment, Phase I most likely will end in 2017. If Phase I is successful, a larger Phase II trial to test efficacy likely would take place in 2018. A successful Phase II trial would be followed by a Phase III trial. Together all three phases of a clinical trial program typically take at least five years.

Last August, scientists from Isis and CHDI Foundation, Inc., the nonprofit virtual biotech firm that funded the early stages of the Isis research starting in 2007, provided extensive details about the plans for the trial. (Click here to read more.).

“The initial development of this antisense drug for Huntington’s disease came out of a longstanding productive partnership between Isis and CHDI, and its advancement now to clinical trial is testament to Isis’ perseverance and scientific expertise,” CHDI president Robi Blumenstein stated in the press release. “It’s exciting that therapeutic candidates grounded in the biology of Huntington’s disease are finally making their way to clinical trial.”

“The initiation of the ISIS-HTTRx study is a significant milestone in the history of Huntington's disease research as this marks the first time a drug designed specifically for Huntington's patients has transitioned into the clinic,” George Yohrling, Ph.D., senior director for mission and scientific affairs for the Huntington’s Disease Society of America (HDSA), wrote in an e-mail. “My hope is that this study not only shows that the drug is safe, but serves as an informative beacon for all future huntingtin-lowering trials.”

Martha Nance, M.D., the director of the HDSA Center of Excellence at Hennepin County Medical Center in Minneapolis and a member of the executive committee of the Huntington Study Group, said that “it would be impossible to overstate the importance of this trial.”

“I am old enough to have grown up in the 1960s, swept up as a young child with the excitement of space exploration, and I remember, almost as clearly and importantly as the Apollo 11 mission that actually LANDED on the moon, the Apollo 8 mission over Christmas 1968, during which William Anders took the iconic picture of the earthrise over the moon,” Dr. Nance wrote in an e-mail. “There were several more steps, several more Apollo missions, before Neil Armstrong could jump off the ladder onto the moon. The ISIS study is the HD equivalent of the Apollo 8 mission.”

LaVonne Goodman, M.D., the founder of Huntington's Disease Drug Works, said that there are "high hopes and expectations" about the trial. "We celebrate those individuals with HD, heroes who are selflessly participating in this trial and all others, 'taking one for the team,'" she wrote in an e-mail.

“We’re very enthusiastic about the drug,” Dr. Bennett said in a 2014 interview.

As he put it previously, Isis technology is like a “laser-guided missile” that targets a specific, disease-causing messenger RNA and destroys it or takes it out of the body “so that you don’t produce that messenger RNA.”

The Isis-Roche partnership

According to the press release, with the initiation of the clinical trial, Isis – a small company – earned a $22 million milestone payment from Roche. To date, Isis has earned $52 million in upfront and milestone payments from the partnership. It can earn more as the project progresses, as well as royalties on potential sales.

Roche can exercise the option to license ISIS- HTT_Rx from Isis through the completion of the Phase 1 trial. If so, Roche will assume responsibility for global development, the acquisition of regulatory approvals, and marketing the drug.

The partnership is critical. Isis cannot alone afford to carry out a clinical trial. Drugs usually cost hundreds of millions of dollars to develop.

According to the press release, Isis’s drug projects include 38 drugs aimed at treating a wide range of diseases, among them cardiovascular disease, metabolic disorders, cancer, and severe and rare diseases, including neurological disorders such as HD.

A huge dose of hope

The announcement of the historic trial’s launch provides a huge dose of hope for the HD community.

Since the discovery of the huntingtin gene in 1993, scientists have published thousands of research papers on HD and identified hundreds of potential “targets” for treatments.

In recent years, scientists and drug companies have initiated an increasing number of clinical trials in the quest for effective treatments. However, to date none has proven successful in halting the disease.

A necessary leap

As seen in animal studies, the infusion of HTT_Rx into the brain has led to the disappearance of the HD-like symptoms.

Scientists warn that it’s a still a huge leap from animals to humans when it comes to testing drugs. Also, only about one in ten clinical trials results in a drug reaching the market.

Earlier this year prominent HD specialist Bernhard Landwehrmeyer, M.D., Ph.D., cautioned that it could still take decades for the gene-silencing approach to play an effective part in managing the disease.

“We should all be extremely excited and hopeful, but remember that there is a lot of work ahead for researchers, doctors, patients, and families before we will get to our moon, and no guarantee of success,” wrote Dr. Nance.

Nevertheless, the Isis-Roche trial is a major step. At a minimum, it will help answer key questions about the gene-silencing approach.

If it is successful in ameliorating symptoms, it could mean the beginning of the end of Huntington’s disease as a threat to the tens of thousands of families affected worldwide.

* * *

Below see links to previous reports on Isis.

"Moving toward a potential treatment: Isis, CHDI researchers outline upcoming Huntington's disease gene-silencing clinical trial"

"A key new ally in the search for Huntington's disease treatments"

"Quickening the pace towards a Huntington's disease gene-silencing clinical trial: pharma giant Roche, Isis enter partnership"

"Designing the best drug possible to defeat Huntington's disease"

"Building a 'laser-guided missile' to attack Huntington's disease"

"Observing the cure in progress"

Also see coverage at HDBuzz by clicking here.

(Disclaimer: I hold a symbolic number of Isis shares.)