Monday, December 11, 2017

Ionis drug successfully reduces toxic Huntington’s disease protein, paving way for Phase 2 trial of effect on patients

In an initial clinical trial that marks a significant step toward finding an effective Huntington’s disease treatment, the Ionis Pharmaceuticals gene-silencing drug safely reduced the production of the toxic mutant protein implicated in HD, the firm announced today.

Ionis has handed development of the expected Phase 2 trial to its partner in the project, the multinational pharmaceutical giant Roche, earning a $45 million license fee, today’s Ionis press release stated. The drug is called IONIS-HTTRx: “HTT” stands for both the huntingtin gene and the protein it produces, and “Rx” signifies a remedy.

The trial was officially classified as Phase 1/2a. A Phase 1 trial measure’s a drug’s safety and tolerability in a small number of participants, while a Phase 2 trial examines efficacy in a larger group of patients. Though mainly Phase 1, this trial had elements of a Phase 2: actual HD patients took part, and it sought to determine whether the drug’s basic mechanism worked.

“We are encouraged by the performance of IONIS-HTTRx in the Phase 1/2a clinical study,” Frank Bennett, Ph.D., Ionis senior vice president of research, stated in the release.

The reductions of the mutant protein “observed in the study substantially exceeded our expectations,” Dr. Bennett added. The study, which involved 46 participants with early HD symptoms, did not assess whether that reduction slowed disease progression.

Ionis stated that “dose-dependent reductions of mHTT were observed” in the trial: the higher the dosage, the greater the reduction in the amount of the mutant protein.

“We were equally encouraged by the safety profile of the drug,” Dr. Bennett stated.

“The results of this trial are of ground-breaking importance for Huntington’s disease patients and families,” stated Dr. Sarah Tabrizi, professor of clinical neurology, director of the University College London’s Huntington Centre, and the global lead investigator on the Phase 1/2a study. “For the first time, a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well tolerated. The key now is to move quickly to a larger trial to test whether IONIS-HTTRx slows disease progression.”


Frank Bennett, Ph.D. (above, photo by Kristina Bowyer, Ionis) and Dr. Sarah Tabrizi (below, photo by Gene Veritas)


Pharma giant Roche steps in

Ionis officials stated in June that a Phase 2 study could start as soon as 2018. Typically, all three phases of a clinical trial project take at least five years, although nobody can predict the actual course of a trial.

In 2013, Ionis, a mid-sized drug-discovery firm that does not produce or sell drugs or conduct clinical trials on its own, partnered with Roche, one of the world’s largest and most successful pharmaceutical companies (click here and here to read more). Roche’s expertise includes neurodegenerative brain diseases.

Roche will now take over the development of IONIS-HTTRx, including the Phase 2 and potential Phase 3 trials and bringing the drug to market. It will hold the license to the drug.

Roche also will administer the open-label extension of the Phase 1/2a study, announced in June, whereby all patients – including those who got a placebo – will continue to receive the drug. The extension allows researchers to gather more data, examine the drug’s effects over a longer period of time, and better prepare for Phase 2. Patients also potentially benefit by receiving the drug longer.

Phase 2 to include United States

By attacking Huntington’s disease near its genetic roots, IONIS-HTTRx could potentially reduce, partly reverse, and even prevent symptoms. Ionis drugs are antisense oligonucleotides, artificial strands of DNA. The drug aims to turn off the huntingtin gene messenger RNA that contains the instructions to make the huntingtin protein in brain cells.

Forty-six patients took part in the Phase 1/2a trial at sites in Canada, Germany, and England.

“Today is an exciting day for the Huntington’s disease community,” a joint Ionis-Roche letter to the HD community stated. “Future studies for the program will be conducted globally, including in the U.S. Roche will announce details about future studies, including eligibility criteria and planned start dates, as this information becomes available.”

More than a decade of research

IONIS-HTTRx resulted from more than a decade of research involving Ionis, Roche, the lab of neurobiologist Donald Cleveland, Ph.D., at the University of California, San Diego, and CHDI Foundation, Inc., the nonprofit virtual biotech firm aimed solely at finding (and funding) HD treatments.

On December 3, Dr. Cleveland received the $3 million Breakthrough Prize, the world’s richest science award, sponsored by Google, Facebook, and other entities. It is twice the value of the Nobel Prize. Dr. Cleveland received recognition for his career contributions to the life sciences, including work on a cause of Alzheimer’s disease. (Click here to read more.)

Dr. Cleveland was honored at the 2012 gala of the San Diego Chapter of the Huntington’s Disease Society of America. For a recent article explaining the Dr. Cleveland’s role in the Ionis project, click here.

In interviews today, I hope to obtain further details about the progress regarding IONIS-HTTRx.

HDBuzz’s take: a historic breakthrough

The HD research site HDBuzz, produced by scientists, stated that today’s announcement is “likely to stand as one of the biggest breakthroughs in Huntington’s disease since the discovery of the HD gene in 1993.”

The site’s article, written by Jeff Carroll, Ph.D. – an HD-gene carrier like me and a scientist dedicating his career to finding HD treatments – asserted that the “most exciting” part of today’s news is that “dose-dependent reductions of mutant huntingtin were observed.”

The clinical trial administrators know this because they examined samples of participants’ cerebrospinal fluid, which runs along the spine and into the brain. Participants received injections of the drug via a spinal tap.

“This means that patients treated with IONIS-HTTRx have reductions in the huntingtin protein in their cerebrospinal fluid,” Dr. Carroll wrote. “Based on this result, it looks like the drug is doing what it’s meant to do, and that huntingtin lowering has been achieved!”

Dr. Wild concluded: “This is a great day in the HD community, and it sets us on the path to even more exciting work in 2018. For the first time in history, HD patients are being treated with drugs known to reduce the amount of huntingtin protein in their brain. Until we conduct the next trial, we won’t know if this reduces the impact of HD. And while we know the drug is safe in the short term, we will also have to watch carefully for any long-term adverse effects. But we’re facing this problem with renewed excitement and hope. It’s the best early Christmas present we could have hoped for.”


Jeff Carroll, Ph.D., at the 2012 CHDI-sponsored HD therapeutics conference (photo by Gene Veritas)

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

Friday, November 10, 2017

A time for hope: HDSA’s 50th anniversary, a record-setting gala, and the impending release of highly anticipated clinical trial results

This year, Pope Francis’ historic “Hidden No More” audience with the Huntington’s disease community has understandably overshadowed another milestone in the HD cause: the 50th anniversary of the Huntington’s Disease Society of America (HDSA).

However, on November 4 the spirit of HDSA, embodied in founder Marjorie Guthrie’s goal of a cure, helped fuel new hopes: the San Diego chapter’s sixteenth gala, recalling HDSA’s start in 1967 and honoring celebrated ESPN sportscaster Chris Berman, raised more than $250,000, a national record for chapters. It was the society’s most successful fundraising event of the last decade.

Also, for the first time, the gala attendees included top scientists from Ionis Pharmaceuticals, Inc., which, by January 2018, expects to release results of its highly anticipated Phase 1 gene-silencing clinical trial.

It was also the first time an HDSA chairman of the board attended: Chair Arik Johnson, Psy.D., the staff psychologist at the HDSA Center of Excellence at the University of California, Los Angeles, joined HDSA CEO Louise Vetter at the event.

It was a striking convergence of history, people, and research progress.

The gala was organized by HDSA-San Diego and the chapter’s former president, Bill Johnston. Johnston left a 38-year career as PR director for the San Diego Chargers football team, which moved to Los Angeles, to keep his HD-stricken wife Ramona at Edgemoor Hospital, an award-winning care facility in nearby Santee. Johnston now works as special advisor to Ron Fowler, the executive chairman and co-owner of the San Diego Padres baseball team and a long-time supporter of HDSA-San Diego.

“It was so rewarding to see the extended HD community having a wonderful evening and enjoying a series of heartfelt and humorous stories about Marjorie Guthrie, the Johnstons and the 2017 Guthrie Awardee, Chris Berman,” HDSA-San Diego President Beth Hoffman, Ph.D., said after the event. “Generosity was in the air, and we’re so grateful to everyone who dug deep to support HD families and to find a cure for HD.”


HDSA CEO Louise Vetter addressing the gala (photo by Derrick Tuskan)

Marjorie Guthrie’s vision for a cure

More than 300 people attended the gala, held at the Pendry San Diego Hotel, including members of the Padres organization, sports and local celebrities, drug company representatives, HD researchers and clinicians, and HD family members.

In her speech, Vetter described HD’s devastating symptoms, its impact on families, and the story of Guthrie’s founding of what would become HDSA after her husband, folk singer and social activist Woody Guthrie, died of HD in 1967. Guthrie began in a time before the Internet: she placed a classified ad in The New York Times seeking contact with other families affected by a disease mainly unknown, even to New York’s medical community.

“In three months, she had 35 families affected by Huntington’s disease that were meeting around her kitchen table and dreaming about developing a cure for HD,” Vetter said. “That’s how the Huntington’s Disease Society of America was born. And at 50 years, we mark the amazing vision that this woman had to really set a course for a community to come together and provide support for one another.”

Today HDSA provides education about HD, supports research, and advocates for better care for HD-affected individuals, Vetter added. It now has more than 40 Centers of Excellence (COE), which provide a variety of family services and involve the community in research studies and clinical trials.

In a pre-gala interview, board chair Johnson outlined some of the ways in which HDSA and COEs are assisting affected individuals and families with HD’s daunting psychological and behavioral symptoms. “We have a Telehealth program for people to call in and talk to a trained social worker or psychologist who has been educated in Huntington’s disease,” he said.

You can watch Vetter’s speech in the video below. Click here to watch my interview with Dr. Johnson.

‘A heart for people that need a voice’

After the audience watched an ESPN report on the Johnston family’s struggles and leadership of the cause, Johnston received a standing ovation as he approached the podium. Johnston’s daughter Hayley, who has not tested for the inheritable genetic defect that causes HD, appears in the video.

“If my wife were here, then it would make sense that you’re standing up,” Johnston told the audience, explaining that Ramona’s advanced symptoms caused her to miss the event for the first time. “My wife is my hero. I appreciate everybody being here tonight. Hayley said it in that video about this disease: people don’t really know what it is until you see it. I wish Ramona could be here. She would be here, if she could.”

Johnston noted that Berman and Fowler have been the “biggest” and “most consistent” contributors to his fundraising efforts. Fowler was honored at the 2013 San Diego gala.

Johnston recalled his friendship with Berman, begun in the 1980s when he started at the Chargers and Berman was at ESPN. Starting in the 1990s, around 6 a.m. every Sunday during football season, Johnston updated Berman on Chargers news for the sportscaster’s reports.

“We just talked football,” Johnston said. “And then when Ramona got diagnosed, I could not have that conversation without him asking first how was Ramona, how are the kids. Every year, at the end of the year, a check would show up in the mail, unannounced, unrequested, a donation. Our honoree has been a huge friend of our organization and the effort to find a cure, find a treatment, for this disease.”

Berman does more than write checks, Johnston added. Berman, he said, “shows to me a commitment and a caring and a heart for people that need a voice, and that’s what this disease needs. It needs people to talk about it, to learn about it. And that’s why we’re doing what we’re doing here tonight.”


Bill Johnston (left) and 2017 Guthrie Award Honoree Chris Berman (photo by Derrick Tuskan)

‘Advancing the ball’ for HDSA

In accepting the Guthrie Award, Berman praised Johnston’s commitment.

“Billy is as loyal as they come,” he said, referring to Johnston’s decision to stay in San Diego. “Is there anything more admirable than that?”

Berman recalled that, after his wife’s death in a car accident in May, Johnston flew to the East Coast for the funeral. Johnston and other “true friends” have helped him overcome his grief, he said.

“You realize that, when times are the toughest, your friends and people bonding together is the way we all can advance the ball, if you will, to use a football term. They’ve helped me do that. And that’s where we are with Bill, and Hayley, who’s here tonight, and the Johnston family and countless other families just like this family.”

You can watch Johnston’s and Berman’s remarks in the video below.


Baking the clinical trial cake

Earlier, I watched as Ionis scientists bid on silent auction items using a mobile phone app. I greeted several of the Ionis officials, including Frank Bennett, the senior vice president for research, who attended the gala for the first time.

Dr. Bennett has overseen the ten-year development of IONIS-HTTRx, a gene-silencing drug that aims to alleviate HD symptoms by reducing production of the huntingtin protein in brain cells. The drug entered a Phase 1 clinical trial in September 2015 in Canada, England, and Germany. The company expects results to become available in the next two months.

Currently, to protect against bias as clinical trial administrators analyze the results, Dr. Bennett and the Ionis HD team cannot access the data. That’s standard clinical trial protocol.

Recalling a metaphor used in formal interviews about IONIS-HTTRx, Dr. Bennett referred to the project as a “cake in the oven.” The team is awaiting the opening of the oven to learn the results.

If successful, IONIS-HTTRx would mark the first effective treatment – though not a cure – for a brain disease.


The Ionis Pharmaceuticals table: (clockwise from left) Chris Bragg, Stacy Raysin (Dr. Bennett's assistant), Eric Swayze, Ph.D., Carolyn Swayze, Lisa Lane, Roger Lane, M.D., Brad Smith, Anne Smith, Ph.D., Frank Bennett, Ph.D., and Paula Bennett (photo by Gene Veritas, aka Kenneth P. Serbin)

Close to treatments

Jody Corey-Bloom, M.D., Ph.D., the director of the COE at the University of California, San Diego, also attended with her husband Floyd Bloom, M.D., staff, and members of the HD community. So did representatives of Teva Pharmaceutical Industries, a major sponsor of HDSA galas and the manufacturer of AUSTEDO, a recently approved drug – developed in San Diego – that alleviates HD’s involuntary movements but does not slow progression of the disease.

On October 30, Dr. Corey-Bloom gave her annual Huntington’s disease research update at the HDSA-San Diego support group. Most of her talk focused on gene silencing and the Ionis trial.

She also spoke on her groundbreaking research on the presence of huntingtin protein in saliva – a potential marker of both disease onset and progression and also of medications’ impact. Saliva is easier and far safer to collect than blood and cerebrospinal fluid, which are also under study for markers. (Click here for a scientific presentation on this topic.)

“This is an incredibly exciting time for HD,” Dr. Corey-Bloom concluded. “I think really we’re on the edge of really discovering something here, and being able to treat this disease. If we can’t cure it, we can slow it down.”

To watch Dr. Corey-Bloom’s presentation, click here.


Dr. Jody Corey-Bloom's table: (clockwise from front) HD family member Linda Pohl, Pablo Garcia, Lily Garcia (Dr. Corey-Bloom's assistant), Steve Granger, Ph.D., chief scientific officer at Salimetrics, LLC, Beth Thomas, Ph.D., The Scripps Research Institute, Dr. Corey-Bloom, Floyd Bloom, M.D., and HD family member Margaret Schroeder (photo by Gene Veritas, aka Kenneth P. Serbin) 

A true celebration of hope

I’ve attended every San Diego gala but one. As always, it was simultaneously exhilarating and emotionally draining.

I was thrilled to see the especially large group of scientists, researchers, and clinical workers. I was able to introduce several of these mutual contacts to each other. I also enjoyed listening to Berman talk about his career as a broadcaster, one of the highlights of the evening (click here to watch an excerpt).

When I greeted Johnston, I told him that my recent, annual neurological checkup showed no signs of HD. I’m 57; my HD-stricken mother’s symptoms started in her late 40s.

However, seeing “HD brothers and sisters” like Tim Schroeder and Sharon Shaffer, both deeply affected by the disease, reminded me of my likely future unless a treatment is found soon.

Yet this gala lived up to its name: a celebration of hope. My heart jumped as I realized it would set a fundraising record.

I’m hoping it will jump even more when the Ionis Phase 1 results come out.


Above, from left to right, Fran Walker, daughter Sharon Shaffer (seated), Taylor Shaffer, Renato, Shaffer, and Alexa Shaffer (photo by Gene Veritas, aka Kenneth P. Serbin). Below, Gene Veritas with HDSA-San Diego supporter Mary Wisco (photo by Bob Walker).



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

(Scroll down for other photo highlights.)



Chris Berman (left) and Ron Fowler, executive chairman and co-owner of the San Diego Padres (photo by Derrick Tuskan)



HDSA-San Diego president Beth Hoffman, Ph.D., (left) and Beth A. Thomas, Ph.D., The Scripps Research Institute (photo by Gene Veritas, aka Kenneth P. Serbin)



Mike and Jan Neil, HDSA-San Diego supporters (photo by Gene Veritas)



Nina Detrow (left), KGTV news anchor Kimberly Hunt, and Lori Ello (photo by Gene Veritas)



Bill and Hayley Johnston (left) with Liya Sharif and Pete Lancia of Qualcomm (photo by Gene Veritas)



The HDSA San Diego Center of Excellence/UC San Diego/Teva table: clockwise, starting in the foreground, Ameera Haque (UCSD research assistant), Gayle Paddison (Teva clinical nurse educator), Mr. Paddison, Amy Rahilly, Jeff Rahilly (Teva), Aeri Kim (UCSD research assistant), Chase Snell (UCSD research coordinator), Sungmee Park (UCSD research coordinator), Ayesha Haque (UCSD research assistant), and Rina Patel (UCSD research assistant) (photo by Gene Veritas)



HDSA-San Diego board member Paul June (middle) with supporters Amy and Cam Stephens (photo by Gene Veritas)



Scott Yoffe and HDSA-San Diego board member Nan Pace (photo by Gene Veritas)



HD family member Doug Schulte (photo by Gene Veritas)



Former HDSA-San Diego president George Essig (standing) toasts with friends (photo by Derrick Tuskan).

Sunday, October 22, 2017

Advocacy in the workplace: raising awareness about Huntington’s disease and brain health

In the fight to defeat Huntington’s disease and other brain disorders, advocacy in the workplace can attract new allies, boost awareness, and serve as a bridge to resources for those facing HD.

November 4 will mark five years since I went public about my gene-positive HD status in my essay “Racing Against the Genetic Clock,” published in The Chronicle of Higher Education.

Before that day in 2012, I lived in the “terrible and lonely HD closet,” with virtually nobody outside the HD community, family, and close friends aware of my family’s struggles. My name appeared nowhere in the local, tri-annual HD newsletter that I wrote and edited from 2001-2007. I began this blog in 2005 with a pseudonym, “Gene Veritas,” “the truth in my genes,” a reflection of my status as an HD-gene carrier.

Starting with the Chronicle article, I have integrated my advocacy into my work as a professor at the University of San Diego (USD).

Bioethical challenges

In 2014, I started collaborating with Laura Rivard, Ph.D., an adjunct professor in the USD Department of Biology who teaches a course on bioethics. One of her students, Nazin Sedehi, recorded a video interview of me recalling my family’s experiences with genetic testing for two websites aimed at helping a general audience explore bioethical dilemmas.

I’ve spoken on HD to Dr. Rivard’s class three times. In February 2016, I gave a presentation titled “Huntington’s Disease and Bioethics: A Personal Case Study.” The talk focused on how advances in medicine and biotechnology have provided new tools for understanding both human biology and the situation of HD-affected individuals and families.

“These changes – these huge transformations that we’ve been going through scientifically and socially – have put people in unprecedented predicaments and thus, they are creating new bioethical challenges,” I stated. I reflected on how HD families faced decisions about predictive testing, family planning, abortion, suicide, euthanasia, and more.

You can watch my presentation in the video below. During the other class sessions, I provided commentary and answered questions after we watched the HBO documentary The Lion’s Mouth Opens, about young filmmaker-actress Marianna Palka’s decision to get tested for HD.

‘You are precious’

My advocacy reached a milestone in May, when I traveled with my family to Rome to help represent the U.S. HD community at HDdennomore: Pope Francis’ Special Audience with the Huntington’s Disease Community in Solidarity with South America. I reported on the audience in several blog posts (click here to read one example).

My trip was made possible by USD’s College of Arts and Sciences, the Frances G. Harpst Center for Catholic Thought and Culture (CCTC), the International Center, and the Department of History. Back home, on September 28 I gave a talk exploring the social, scientific, and religious meaning of this extraordinary event. Some 60 students, faculty, and members of the San Diego HD community attended.

In one of the most emotional speeches I have given, I repeated the words of Francis’ address that most moved me:

For Jesus, disease is never an obstacle to encountering people, but rather, the contrary. He taught us that the human person is always precious, always endowed with a dignity that nothing and no one can erase, not even disease. Fragility is not an ill. And disease, which is an expression of fragility, cannot and must not make us forget that in the eyes of God our value is always priceless. Disease can also be an opportunity for encounter, for sharing, for solidarity. The sick people who encountered Jesus were restored above all by this awareness. They felt they were listened to, respected, loved. May none of you ever feel you are alone; may none of you feel you are a burden; may no one feel the need to run away. You are precious in the eyes of God; you are precious in the eyes of the Church!

I told the audience: “I saw HD turn my mother into a shadow of herself. I deeply fear losing my ability to speak and, especially, to write. Hearing that we HD people are ‘precious’ was a huge morale booster.”

I hope that my presentation raises awareness about HD in the U.S. Catholic community and beyond, and helps spur at-risk individuals and others to exit the HD closet and join the movement.

You can watch the speech in the video below, recorded and edited by Scott Lundergan of USD media services.


Warning about football’s dangers

On October 17, another dimension of my workplace advocacy – the effort to raise awareness at the university about the dangers of tackle football – reached a crescendo. A resolution to ban football at USD, proposed by Daniel Sheehan, Ph.D., Nadav Goldschmied, Ph.D., and me, was voted on in the Academic Assembly of the College of Arts and Sciences.

USD football is a non-scholarship sport, so its profile is not as high as at some campuses, but it has fervent fans among students, alumni, and even faculty. At a USD Faculty Senate meeting last December, President James T. Harris III, D.Ed., reaffirmed his opposition to cancelling the program because, in his words, “no universities have closed their football program […]  because of concussion evidence yet.”

In the weeks leading up to the meeting, I remembered Pope Francis’ encouragement. I also frequently recalled my mother’s struggle with HD and my father, the “HD warrior” who cared for her for more than a decade.

Our resolution focused on the scientific evidence about football’s threat to the brain, especially the disease known as CTE (chronic traumatic encephalopathy), first seen in boxers in the 1920s and, over the past ten years, identified in the autopsies of an increasing number of National Football League, college, and high school players. We cited the publication in July of an article in the Journal of the American Medical Association documenting CTE in 110 of 111 autopsies of decease NFL players. (For the resolution’s rationale, please click here).

CTE produces symptoms similar to HD and other neurological diseases such as aggressiveness and cognitive loss.

However, many faculty members defended the football program because of virtues such as character-building. Surprisingly, this group included biologists and other natural science specialists.

After one of the most heated faculty debates I have witnessed in 25 years at USD, the motion lost, 50-26. However, 30 professors abstained – reflecting perhaps discomfort about offending their colleagues and/or indecision on the matter.

As a brain health advocate, I was disturbed by the vote. In an upcoming article, I will explore the USD debate in detail, in particular how it shows how scientific evidence is often ignored or manipulated in critical debates, and what this means for the HD and other disease communities.

Immediately after the assembly, I met with about 70 members of USD’s chapter of Phi Delta Epsilon, the co-ed pre-medical fraternity, to speak on HD and the papal audience. I urged them, as future members of the health professions, to be aware of CTE and to safeguard the well-being of football players. I also defended the continued inclusion in our health system of those with pre-existing conditions like me who in the past often hid their potential illnesses.

Fraternity president Nicholas DiChristofano pledged that the organization would support the HD community.

A student stands up for her family

As a result of my public stance, USD faculty members, students, and former students have supported the cause with generous donations and participation in the annual Team Hope Walk of the San Diego Chapter of the Huntington’s Disease Society of America (HDSA). Many read this blog.


The Serbin Family Team of the 2014 HDSA-San Diego Team Hope Walk: from left to right, Dory Bertics, Bianca Serbin, Jane Rappoport, Gary Boggs, Prof. Yi Sun (of the USD History Department), Gene Veritas (aka Kenneth P. Serbin), Regina Serbin, and Allan Rappoport (photo by Bob Walker)

Through my advocacy, I can connect people to HDSA’s resources.

At day’s end on October 17, I met with Sydney Smyer, a 19-year-old USD biology major.

On October 3, Sydney had sent me the following email, quoted here with her permission:

My name is Sydney Smyer. I am a student here at USD and I attended your talk on Huntington’s disease and the explanation of His Holiness, Pope Francis’ involvement in the Huntington’s disease community. I was quite moved and enlightened, Dr. Serbin. Huntington’s disease runs in my family. My grandfather died from it as well as his father and three of his brothers. His remaining brother has recently been diagnosed with Huntington’s disease. Soon I will be tested, especially because my mother refuses to be tested and my uncle has been showing symptoms for some years now. I think your words would enlighten my family and bring them to the fullness and understanding that is comforting in so much uncertainty for our family members.

Sydney, whose family is Catholic, will share my #HDdennomore video with her family. They have an extremely rare disease known as HDL1, Huntington’s disease-like syndrome, a genetic disorder producing HD-like symptoms.

Sydney and I talked for almost an hour about our journeys with HD. Though I mentioned my own past fears about my HD status jeopardizing my career and insurance, Sydney was adamant about facing HDL1 openly and standing up for her family.

She accepted my invitation to the October 30 meeting of the HDSA-San Diego support group, featuring the highly popular annual HD research update by Jody Corey-Bloom, M.D., Ph.D., the director of the local HDSA Center of Excellence for Family Services and Research.

Stepping forward

To me, there is no more important work in the HD community than the mutual assistance we provide at the support group.

When I exited the HD closet five years ago, I did not imagine that one day a USD student would join our group.

I am grateful to USD and my colleagues for their support as the HD community seeks a treatment for this incurable disorder.

As a professor, I have the privilege of melding my academic work with advocacy.

However, many of us in the HD community have unique skills and positions with the potential for building bridges to our employers and others we associate with on personal and professional levels. Doing so can reap many unexpected benefits.

Sydney's courage should inspire us all to step forward.

Tuesday, June 27, 2017

Ionis Huntington’s disease drug a step closer to a critical Phase 2 study


Ionis Pharmaceuticals has made two positive announcements about the historic Phase 1 clinical trial of its gene-silencing drug for Huntington’s disease: trial enrollment is complete, and the company will extend the study for all patients who complete Phase 1.

These are key steps on a multi-year path to possible Phase 2 and 3 trials that, if successful, would bring the trial drug, IONIS-HTTRx, to market. Typically, all three phases of a clinical trial project take at least five years, although nobody can predict the actual course of a trial.

IONIS-HTTRx aims to alleviate HD symptoms by reducing production of the huntingtin protein in brain cells (click here to read more). Ionis launched the Phase 1 trial in September 2015. Three dozen patents are taking part in the trial, expected to be completed by the end of 2017, at sites in Canada, Germany, and England. This first phase aims not to assess success in combating HD but rather simply whether the drug is safe and tolerable.

It marks the first time HD patients are receiving a substance aimed to attack the genetic causes of the disease. It’s also the first time they’re getting a drug via spinal injection.

“The safety and tolerability profile of IONIS-HTTRx in the completed cohorts of the Phase 1/2a study supports its continued development,” a June 22 Ionis news release stated. “Patients who complete the Phase 1/2a study will be eligible to participate in an open-label extension (OLE) study that Ionis plans to initiate in the next several months.”

“Open label” means all participants take the drug, in contrast with a “double-blinded” clinical trial like the current Phase 1, where half the patients receive a placebo and neither patients nor doctors know who is receiving the actual drug.

This month’s news provided the strongest indication so far that Ionis and its partner Roche, a much larger multinational pharmaceutical firm with vast clinical trial experience, will take IONIS-HTTRx into a larger, critical Phase 2 study, as early as 2018, to measure efficacy.

“Upon completion and full analysis of this study, the next step for this program will be to conduct a study to investigate whether decreasing mutant huntingtin protein with IONIS-HTTRx can slow the progression of this terrible disease," Frank Bennett, Ph.D., the Ionis senior vice president of research, said in the release.

Ionis has repeatedly indicated that a Phase 2 study would include U.S. trial sites.


Frank Bennett, Ph.D. (photo by Kristina Bowyer, Ionis)

‘Cautiously optimistic news’

The double-blinded protocol of the Phase 1 HTTRx trial insures that bias and other external factors don’t affect the trial results.

As noted, in an OLE each participant receives the actual drug, and usually at the highest dose tried in Phase 1. An OLE allows researchers to gather more data, examine the drug’s effects over a longer period of time, and better prepare for an eventual Phase 2. Patients also potentially benefit by receiving the drug longer.

The HD research website HDBuzz, which is produced by clinicians and scientists, described the Ionis announcements as “cautiously optimistic news.”

“News that the trial is fully recruited and the final patients are going through the procedures is a strong suggestion that even at the highest doses, the drug’s safety looks good,” the HDBuzz report observed. “Despite exhaustive safety testing before going into patients, any drug can produce unwanted effects, so that’s really the best news we could be hoping to hear at this stage.”

Regarding the open-label extension, it added, “We don’t want to read too much into a brief announcement, but running an OLE isn’t cheap for a trial sponsor, so this announcement certainly gives us optimism about the whole HTTRx program.”

Signs of HD in the blood

A separate research study, with results published June 7, could help Ionis and Roche researchers evaluate the results of the Phase 1 trial and plan the potential Phase 2 trial.

In what was described as a “major advance in the field of Huntington's disease and neurodegeneration in general,” a team of researchers has identified a potential blood biomarker for HD.

Biomarkers indicate a disease mechanism or drug impact. They are common for many diseases, but the complexity and inaccessibility of the brain have made it extremely difficult for researchers to find them for neurological diseases.

HD scientists have most recently focused on obtaining biomarkers from the cerebral spinal fluid (CSF). However, obtaining CSF, which requires puncturing the spine, is far riskier than drawing blood, the technique used in the new biomarker research.

Led by Ed Wild, M.D., Ph.D., one of the administrators of the IONIS-HTTRx trial in England, the new biomarker study demonstrated that a brain protein known as neurofilament light chain (Nfl) appears in the blood of HD patients and presymptomatic gene carriers. (Click here and here to read more.)


Dr. Ed Wild (photo from EdWild.com)

A less invasive measurement

Dr. Bennett of Ionis previously described Nfl as a protein involved in the cytoskeleton, or internal “scaffold,” of neurons. HDBuzz likened it to “the ribs of an umbrella.”

Dr. Wild’s team discovered that, the more advanced the stage of HD, the greater the amount of Nfl in the blood.

“This suggests that a blood test might be able to provide consistent information about the brain, in place of an invasive spinal tap,” HDBuzz commented. “We hope [Nfl] will be added to the arsenal of resources that are helping us to monitor HD and to develop new therapies.”

Indeed, the IONIS-HTTRx researchers previously noted that Nfl is one potential biomarker in the Phase 1 trial.

Further research is underway to confirm the Wild team's results and to determine to what extent Nfl can be used as a biomarker.

Pope Francis, Ionis, and the hope for a cure

The Ionis announcements about the clinical trial came as the 32nd annual convention of the Huntington’s Disease Society of America got underway in Schaumberg, IL. In addition to the news release, Ionis issued a letter to the HD community.

“We can assure you our number one goal remains our commitment to advancing IONIS-HTTRx development, a drug that has the potential to transform the treatment of HD,” the letter stated.

The positive news also comes in the wake of HDdennomore, the historic audience of the Huntington’s disease community with Pope Francis in Rome on May 18.

Dr. Bennett made a substantial donation to HDdennomore. He and several Ionis officials attended the audience. Dr. Bennett and his wife Paula sat in the front row along with leading HD scientists and dignitaries. They were greeted by Francis.

In his address, the pope recognized the geneticists and scientists “present here, who, for some time, sparing no energy, have dedicated themselves to studying and researching a treatment for Huntington’s disease. Clearly, there is a great deal of expectation surrounding your work: resting on your efforts are the hopes of finding the way to a definitive cure for the disease, but also of improving the living conditions of these brothers and sisters, and of accompaniment, especially in the delicate phases of diagnosis, at the onset of the first symptoms.”

If it succeeds, IONIS-HTTRx could fulfill those hopes and show the way to curing other neurological diseases.


Frank Bennett (left), Paula Bennett, and Gene Veritas (aka Kenneth P. Serbin) in St. Peter’s Square just before the audience with Pope Francis, May 18, 2017 (photo by Bianca Serbin)

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

(Click on the links below for past coverage of the Ionis HD project.)










Tuesday, May 30, 2017

Join the Facebook Live event (soon!) on Pope Francis’s historic audience with Huntington’s disease families


I want to invite the Huntington’s disease community – and all potential new supporters of the cause – to participate in my Facebook Live interview about Pope Francis’s historic HD audience on Wednesday, May 31, at 11 a.m. Pacific Daylight Time.

Conducted by San Diego Union-Tribune reporter Bradley Fikes, the interview will take place at this link: j.mp/sdutface. Participants can send questions and comments.

The interview will discuss details of the papal audience, where Francis declared that HD should be “hidden no more.” It will also allow for reflection on the significance of the event for the HD movement. (Click here to watch highlights of the audience).

Building on #HDdennomore’s goal of increasing global awareness of HD and removing the shame associated with the disease, we in the HD community can use the interview to expand our base of supporters.

Please invite others beyond your regular circle of friends, relatives, and acquaintances to watch.


Gene Veritas (aka Kenneth P. Serbin) with Pope Francis, who is holding a picture of Gene's late mother Carol Serbin, a victim of HD, and her long-time caregiver, the late Paul Serbin (photo by L'Osservatore Romano)

Sunday, May 21, 2017

Francis made a day of ‘superlatives’ for the Huntington’s disease community, says event co-organizer

Pope Francis created a moment of “superlatives” for the Huntington’s disease community in his historic May 18 meeting with HD-afflicted families, international advocate Charles Sabine said a day later, citing record involvement in the cause, global awareness, and a “poignant” focus on HD’s tough challenges.

A former foreign correspondent for NBC News and presymptomatic carrier of the HD gene, Sabine helped organize HDdennomore, Pope Francis’s Special Audience with the Huntington’s Disease Community in Solidarity with South America” (click here for background on the event).

Sabine, as did prominent HD scientist and Italian senator-for-life Elena Cattaneo, read an introductory statement preceding Francis’s own speech.

“Your Holiness, today marks a new chapter in the history of humanity’s forgotten families,” Sabine told the pontiff as the audience and web viewers from around the planet listened. “Never before has a world leader recognized the suffering of Huntington’s patients and their carers.”

He described HD as the “harshest affliction known to mankind” and also the “most misunderstood, and until today, the most hidden.” Despite that, Huntington’s has never defeated the human spirit, Sabine asserted. Francis could now affirm that “it is not a sin” to have HD.

Thanking the pope on behalf of the HD community, Sabine praised Francis’s “wisdom” and “compassion, which has shone the light of your church on our disease, at last, so that it be hidden no more.”

In his own stirring speech, Francis elaborated on some of Sabine’s points and declared that HD disease should indeed be “hidden no more!”

Visiting the HD families

The day after, Sabine visited the several dozen HD family members from South America, a main focus of HDdennomore, at their lodgings, the Passionist fathers’ monastery. Located in the historic center of Rome just south of the Colosseum and with a large inner courtyard, the monastery provided the HD families with an idyllic setting for repose and meals. HDdennomore provided transportation to the Vatican and other sites during the week-long stay in Rome.


Charles Sabine (center, white shirt), flanked by HDdennomore co-organizers Ignacio Muñoz-Sanjuan, Ph.D., and Senator Elena Cattaneo, Ph.D., and surrounded by South American HD family members (photo by Gene Veritas, aka Kenneth P. Serbin)

The guests included the juvenile-HD-afflicted 15-year-old Brenda of Buenos Aires, Argentina, the pope’s hometown, and 13-year-old Anyervi, a member of an HD family from Venezuela’s Lake Maracaibo region, the site for decades of critical research in the search for the HD gene led by Nancy Wexler, Ph.D., who attended the event. Both Anyervi and Brenda have been ostracized by other children because of prejudice regarding HD.

Before the pope’s arrival for the audience, Sabine called the two on stage individually. Anyervi received a soccer ball and jersey signed by Brazilian soccer superstar Neymar, who greeted the boy in a short video. Brenda was serenaded in person by Argentine smash-hit singer-songwriter Axel.

Sabine’s reflections

At the monastery, an upbeat Sabine circulated among the families and HD advocates, conversing and joking. He took a break to speak with me about his impressions of the event in its immediate aftermath.

GV: What is your feeling about the meeting with the pope?

CS: It’s mostly a feeling of immense relief that, after a year and a half of planning, on a day when a more than a million things could have gone wrong, nothing major did. That’s my immediate sense.

But I’m so extraordinarily pleased at the words of Pope Francis. That was beyond my control other than the set of notes which I gave him in preparation, which he requested, about the disease. He could not have been more eloquent, poignant, and to the point and focused on the real problems and issues that you and I and everyone else faces with this disease.

And he eloquently and, I believe, truthfully and sincerely made the point that this disease should be – and he used these words – “hidden no more.” And that is something that I could never really have dreamt would happen in my lifetime.

GV: That he’d actually use those words?

CS: Yes. But he did say – and this is important – that it is a great slogan but that it must become more than just a slogan. That’s now what we’ve got to do.

GV: So that’s the question, Charles: what comes next for “HDdennmore” and this whole movement?

CS: Well, I was a little surprised when I read in The Washington Post this morning that the “HDdennomore” event in the Vatican yesterday was the beginning of an initiative. That sounds a little bit daunting. It was the initiative to me! To hear it described as a beginning is both daunting and exciting. Okay, I’ll take that. Let’s call this just the beginning. Where next? Washington? London? We’ll see.

GV: So you’re kind of basking in the joy of this for the time being?

CS: Yeah, I’m just so pleased for all of these families who are standing here in this courtyard of this peaceful Passionisti convent here in Rome with all of these patients. I saw many of these patients a month ago in their homes in Maracaibo. Physically they appear better. They are absolutely flying. They are all smiling, they’re all laughing, they’re all talking.

Okay, they have just had a pretty amazing experience, but it just shows really what can happen. Already we’ve had messages from all over the world of people not only just congratulating us. I’m stunned how many people watched the event. I had no idea that so many people would watch it. I’ve had messages from people who were watching it in the middle of the night on the West Coast. There was one nurse whose family were watching it in the Philippines. People were watching this all over the world.


South American HD families preparing for a group photo at the Passionist fathers' monastery, May 19, 2017 (photo by Gene Veritas)

The reaction has already been intense. We’ve had messages of just not support for the event, but also financial bequests. Anyervi, the little 13-year-old who got the Neymar shirt, he’s already had a wealthy benefactor in Italy who’s asked to sponsor him now for the rest of his life. We’ve had other requests to help.

We had a meeting just yesterday, which followed after our event, with industrialists who are looking into ways in which they can help South American families, in particular in Venezuela, where one of them has land he’s donating now with a view to providing food. There was a clinicians’ meeting after that. They were coming up with ideas for working together to get drugs and medical services into South America. It’s already happening.


Anyervi of Venezuela (photo by Gene Veritas)

GV: Did you have a meeting with a cardinal and/or other people in the Vatican afterwards?

CS: Yes, I wasn’t present at them, but there have also been meetings with cardinals to get across the points that Pope Francis made so eloquently and directly about how this disease has been ignored.

And he admitted it. He was very frank. The pope said and was implicitly admitting that his church had failed. He didn’t want to say it like that, but he said these people have been ignored. He didn’t say these people have been ignored, but not by the Church. He said they’ve been ignored. That means they’ve been ignored by the Church. And that’s a wonderful admission.

What we need to do now is to insure that his words are now made into actions on the ground by the cardinals, the archbishops, and the priests across not just South America but all around the world to make it understood that this should be a disease that no one should feel, as I said in my words there, that it is a sin. I spoke to the pope yesterday. I said thank you for making clear the truth – one of the truths that’s been omitted from this disease for centuries – which is that it’s not a sin to have Huntington’s disease in your family.

GV: The pope mentioned the issue of embryonic stem cells. Do you want to comment on that?

CS: It was a little bit of a shame that he did that. It’s the one thing about that speech that was a little bit disappointing. I don’t think he needed to get into that because it wasn’t particularly relevant to that event.

Unfortunately, many of the newspapers from around the world have taken that as a headline, which is a bit of a shame. [The Pope stated that no scientific research, no matter how “noble” its goal, “can justify the destruction of human embryos.”] Of course, that’s an issue that’s still a stumbling block with the Catholic Church. But I personally don’t think that for one second his mentioning that in his talk should take one iota away from the fact that it was a resounding, total success.


Pope Francis during the HDdennomore special audience (photo by Gene Veritas)

GV: Do we know who wrote the pope’s speech?

CS: I don’t know. I gave him three pages of notes that talked about what we go through, including, in particular, the shame and the stigma. And certainly the themes that were in that I saw in there. I don’t whether he wrote it or if he had others. But they wrote it very, very well.

It was really, I thought, brilliantly working in, as he would naturally, the point of mercy and Jesus. The event yesterday personified yesterday more than any other event exactly that new philosophy of his of putting mercy before doctrine, which is not a popular one amongst many on the right.

But the fact is, there were so many superlatives yesterday. There were 1,700 people there, according to the Associated Press and Reuters. That was by far and away the largest collection of people with regard to Huntington’s disease, by some measure. There were 150 patients – at least – that were there, and probably a lot more. That in itself is another record. There have never been that many people in one room affected by Huntington’s disease. There could have been people in there affected by disease that we didn’t meet.

There were at least 27 countries represented. I don’t know whether that’s a record, but certainly the other two are.

(My trip to Rome was made possible by the College of Arts and Sciences, the Frances G. Harpst Center for Catholic Thought and Culture, the International Center, and the Department of History of the University of San Diego. I am grateful for the institutional and moral support of my colleagues and students.)