Defeating Huntington’s disease starts with taking care of yourself and joining Enroll-HD

For those of us affected by Huntington’s disease or at risk for it, the fight against the disorder begins by taking care of ourselves.

This idea occurred to me during my daily morning meditation on Jan. 14, 2016, as I anticipated my annual checkup in the Enroll-HD program later that day.

Many people struggling to come to terms with HD ask: with so much to worry about, how can I contribute to the cause?

You can start simply by committing to care for your health and asking family members and others to help monitor your condition. In doing so, you will help your family, too, by preparing for and perhaps even diminishing the current or eventual caregiving burden associated with Huntington’s.

You can extend that assistance to the entire HD community by joining Enroll-HD, a worldwide registry of affected individuals, asymptomatic HD gene carriers, untested at-risk individuals, and other family members. With its growing database, Enroll-HD serves as a platform and research project aimed at facilitating clinical trials and the discovery of treatments.

The greater the participation in Enroll-HD, the faster trials can take place.

Helping the researchers

Not long after learning of my own risk for HD in 1995, I started participating in research projects based at the University of California, San Diego (UCSD), and San Diego State University (SDSU) (click here to read about one example).

In January 2015, shortly after my participation in the PREDICT-HD study ended, I registered in Enroll-HD.

At this month’s follow-up visit at the UCSD Huntington’s Disease Clinical Research Center, I once again gave blood that scientists can use in the numerous research projects facilitated by Enroll-HD. I also underwent a battery of cognitive tests.

In addition, I participated in four research projects by scientists at UCSD, SDSU, and other local institutions. Two involved standing on high-tech platforms designed to detect  balance problems in people who have brain disorders and concussions. Another involved a measure of fine motor skills, which are seriously affected in HD, by writing on a special tablet connected to a computer.

Finally, I spit into a tiny collection tube for a project involving the detection and study of the huntingtin protein in saliva. Abnormal huntingtin causes HD.

Gene Veritas (aka Kenneth P. Serbin) writing on an experimental tablet (above) and standing on a platform to detect balance problems (below) (photos by Ayesha Haque)

A neurological exam

My visit concluded with a standard neurological exam by Jody Corey-Bloom, M.D., Ph.D., the director of the UCSD clinic. Among other tasks, I had to follow her fingers with my eyes, rapidly tap together my thumb with my index and middle fingers, and walk down a straight line for about 25 feet.

To my great relief, Dr. Corey-Bloom noted no irregularities! At 56, I am now past the point at which my HD-stricken mother displayed the characteristic involuntary movements.

Afterwards, I discussed with Dr. Corey-Bloom my questions and concerns about my potential participation in the SIGNAL clinical trial to test a monoclonal antibody as an HD treatment.

I will soon provide an update on SIGNAL.

Enroll-HD’s positive impact

The next day, I obtained the latest news about Enroll-HD from Joe Giuliano, the director of clinical operations for CHDI, the multi-million-dollar nonprofit virtual biotech aimed exclusively at developing HD treatments. In collaboration with HD research centers and clinics around the globe, CHDI sponsors Enroll-HD.

Enroll-HD officially launched in July 2012. According to Giuliano, as of January 15, nearly 9,000 individuals from 14 countries and 140 sites had signed up.

Has the program met CHDI’s expectations?

“I think there’s a high level of engagement among the patient community and among the investigators around the world,” he said during a phone interview. “The recruitment has been excellent. We could have 10,000 participants by the end of March, which would be amazing. I’m really pleased with how well the availability of the dataset and the biological samples [blood] has worked out. In other words, people are using the data, and the data is available through the website. It’s a great example of making data available quickly.”

What’s been the impact?

“We’ve been actively assisting three clinical trials that have been going on – PRIDE, Amaryllis, and LEGATO – with their recruitment,” Giuliano continued. “We have released our second periodic dataset, with 4,150 participants. There are 28 projects that are currently using Enroll-HD data, to answer different research questions. We’ve been actively distributing biological samples for a variety of projects.”

As a result of Enroll-HD, scientists are deepening their understanding of the disease, and doctors are finding ways to improve care.

Enroll-HD contributes directly to the quest for treatments. The larger the number of potential clinical trial volunteers, the greater the chance that trial administrators can enlist the required number for each trial. The number of HD trials has increased each year, increasing the demand for volunteers. Without the trials and the volunteers, scientists can’t test treatments.

Joe Giuliano (left) and Gene Veritas at a 2015 CHDI conference

Challenges in Latin America

On the downside, in one key region, Latin America, Enroll-HD has progressed “very slowly,” Giuliano said. So far, Enroll-HD is only operating in Argentina and Chile.

In October 2015, the National Research Ethics Commission in Brazil – the world’s sixth largest nation, with an estimated 20,000 HD-affected individuals – rejected the proposal to set up Enroll-HD there.

“Obviously we were very disappointed,” Giuliano said. “I think the National Research Ethics Commission rejected based on some areas where there was a perception that the Enroll-HD study was not aligned well with some of Brazil’s legal precedents.”

However, Giuliano said that Enroll-HD will step up efforts to involve Latin America’s HD families. With growing interest in Colombia, that country be the next to join Enroll-HD, he said.

“We’re working harder than ever,” Giuliano affirmed. “You haven’t heard the end of us in Brazil. We’re really committed to Latin America. Many of us believe that Latin America, like in the beginning of their history of HD research in Venezuela, which played an important role – now in the later stages of HD research it’s going to resurge, reawaken, and become an important player in HD research again.”

In a future article I will explore the Brazil decision in depth as well as ways HD families can push for greater acceptance of Enroll-HD there and in other countries of the region.

Building a common cause

As I approach the inevitable onset of HD and feel many of the other effects of normal aging, I realize more than ever the need to stay in shape via a healthy diet, daily stretching and aerobics, meditation and spirituality, and psychotherapy.

Without health, I cannot work, dedicate myself to my family, or advocate for the HD cause.

Caregivers, the "HD warriors" who enter the trenches each day, must also seek opportunities for respite.

With the significant progress towards HD treatments of recent years and growing awareness of the importance of HD and other neurological disorders, advocates have a busier agenda than ever.

I am thrilled to assist HD research and the implementation of the critical clinical trials by taking part in Enroll-HD.

After following the HD movement in Brazil for two decades and participating in the historic sixth World Congress on Huntington’s Disease there in September 2013, I aim to join my Brazilian HD brothers and sisters to advocate for reconsideration of the government’s rejection of Enroll-HD.

We must not lose the momentum in Brazil and Latin America!

Only by building this common cause can we ultimately defeat HD.

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)