‘Let’s Talk About Huntington’s Disease’: 2019 HD Awareness Month kicks off

May is Huntington’s Disease Awareness Month. As in past years, the Huntington’s Disease Society of America (HDSA) is encouraging HD families to share their experiences in a social media campaign, #LetsTalkAboutHD.

Other HD advocacy groups are also marking HD Awareness Month.

As a presymptomatic HD gene carrier who lost his mother to HD in 2006, I kicked off my own participation as a guest May 1 on Help 4 HD International’s podcast Help 4 HD Radio (click here to hear the program.)

I recalled my family’s struggle with HD in an interview with podcast host and HD gene carrier Lauren Holder, the Help 4 HD Radio producer and the 2014 HDSA Person of the Year.

“We need to continue telling our stories,” I said in response to Lauren’s question about how to promote HD Awareness Month, emphasizing the need to attract those unaffected by HD to our cause.

I also highlighted the “real hope” for the first effective HD treatments with clinical trials such as the Ionis-Roche project. These trials are “really unprecedented in the history of HD,” I noted. In the mid-1990s, when my mother was diagnosed, there had been “zero hope,” I recalled.

The next day, I posted HD Awareness Month flyers on my office door at the University of San Diego.

I’m ready for #LetsTalkAboutHD!

Gene Veritas, aka Kenneth P. Serbin, at his office at the University of San Diego (photo by Yi Sun, Ph.D.)

A painful silence

My conversation with Lauren stirred up painful memories – but also provided fresh insight – about my own path from refusing to talk publicly about HD to exiting the “terrible and lonely HD closet” in 2012 with an essay, “Racing Against the Genetic Clock,” in The Chronicle of Higher Education.

Regarding my “coming out” about HD, Lauren wanted to know: “How did it make you feel? Was the process hard? Did you feel a sense of relief?”

“Deep down, I knew that someday I would need to go public, in some way or another, because it’s very hard to be an advocate without telling people about your story,” I said.

I recounted one poignant dilemma – discussed in public for the first time in the podcast – in the early 2000s. Back then, HDSA-San Diego was joining other chapters around the country in hosting the organization’s first fundraising galas.

“I would volunteer for the galas,” I told Lauren. “I was writing the newsletter that we would distribute at the galas. But I would never tell anybody my story.”

I was known in other San Diego circles for my work as a scholar of Brazil, and once I had given a local public talk on that country.

“I had met this one couple [at my Brazil talk],” I explained to Lauren. “And then, a year or two later, they showed up at one of our galas. So it was like, ‘Wow!’ They were wanting to know what I was doing at this gala here. And I said, ‘Well, this is my personal commitment to charity and making a difference.’

“And I didn’t tell them my story,” I explained. “It’s that kind of situation that was very difficult for me, because I was afraid of being outed, because nobody at my work knew my status. I was worried about losing my job and losing my insurance, and, if I were ever to switch jobs, could I get health insurance again? All of the concerns that people in our community, and other communities, have.

“I really just felt bad that I couldn’t – and wouldn’t at that point – share my story.”

Becoming an open, honest advocate

Going public “allowed me to be a much, much better advocate, an honest advocate,” I told Lauren. “I can talk openly about HD and my family situation.”

My essay “Racing Against the Genetic Clock” shocked my colleagues at work and around the country, I recalled.

However, I believed that the article was necessary because I “wanted to take away the fear of talking about Huntington’s disease” for others.

“To this point, I have not, to my knowledge, suffered any discrimination,” I added “And, of course, I’m still asymptomatic. Who knows what will happen if and when I become symptomatic? Things could change.”

However, until now, “I’ve been treated with respect,” I said. Living outside the “HD closet” has “been a very positive experience.”

The prohibition of insurance discrimination for people with pre-existing conditions in the Affordable Care Act and the passage of the Genetic Information Nondiscrimination Act have further encouraged me, I added.

#LetsTalkAboutHD!

Going public about one’s HD story is a “personal decision,” I observed.

Those unready to tell their stories openly can still participate in #LetsTalkAboutHD by starting with relatives and close friends, I said.

In the HD community, we all have important stories.

As I’ve told Lauren and so many others, “Together we will defeat HD!”

Sadly, HD and juvenile HD patients continue to die. HD Awareness Month provides our community with the opportunity to renew our energies and tell the world of the urgent need for treatments.

This Thanksgiving, appreciating stable health and new plans for Huntington’s disease advocacy

This Thanksgiving, I am especially grateful for good health – and all that it enables me to enjoy.

At my annual neurology checkup on October 31, the doctor told me that I remain asymptomatic for Huntington’s disease. My more extensive annual Enroll-HD examination earlier in the year also showed no symptoms. 

I tested positive for the HD gene in 1999. Next month, I turn 59. At that age, my mother had already been diagnosed and was rapidly losing the ability to walk, talk, and care for herself. She died in 2006 at the age of 68 after a long struggle.

I never imagined that at this point I could still pursue my passion for writing, teach at the university, and support my family.

As I frequently tell students, colleagues, and my family, “health is first.” Without it, achieving goals and handling responsibilities can become very difficult, if not impossible.

Studying the history of the HD cause

I am putting the final touches on a book in my field of Brazilian history, scheduled to be published next June, From Revolution to Power in Brazil: How Radical Leftists Embraced Capitalism and Struggled with Power. I began the research more than two decades ago, not long after learning of my mother’s HD diagnosis. Seeing the project come to fruition is thrilling and profoundly fulfilling.

With the Brazil project complete, I will carry out my long-gestating plan to shift my main scholarly focus to the history of science, technology, and medicine. Last month I proposed a new, multi-year research project, titled “Racing Against the Genetic Clock: A Social, Scientific, and Personal History of the Huntington’s Disease Movement.”

I aim to study how key facets of the movement intertwined with major developments in the biotechnological and medical revolutions of the past 200 years. I believe that the HD cause can serve as a guidepost for other disease communities and inform key bioethical questions related to them.

I also want to help the HD community reflect on its path through history. 

More than ever, my scholarly work and HD advocacy will meld. (Click here to read more.)

Seeing our daughter enter college

On a personal level, good health allowed me to join my wife Regina last August in helping our HD-free daughter Bianca set up for her first semester at the University of Pennsylvania, where she is studying in its College of Arts and Sciences.

I had always feared that HD would prevent me from experiencing this special moment – just as HD had stopped my mother from interacting with Bianca as a baby and young child.

I am more determined than ever to see Bianca graduate from college and find her way in life. I’m hoping that GENERATION HD1, the historic Roche Phase 3 clinical trial of a gene-silencing HD drug, will result in an effective treatment not only for patients, but as a preventive measure for presymptomatic gene carriers like me. Roche hopes to enroll the first volunteers starting in early 2019.

Looking ahead, I hope to retire on my own timeline – not because of HD.

Regina, Bianca, and Kenneth Serbin (aka Gene Veritas) during Penn Family Weekend, October 21, 2018 (family photo)

The preciousness of life

I’ve been extremely fortunate to reach this point without HD symptoms—or other significant health problems. Many HD brothers and sisters of my generation are struggling with symptoms. 

Like so many in HD families and other difficult situations, I’ve learned to value each moment of life.

Others face different health issues. At this time last year, I lost two wonderful friends about my age, generous supporters of the HD cause, taken quickly and unexpectedly by other conditions. I’ve missed them dearly, and think about them daily as a reminder of the preciousness of life.

Tomorrow, I want to enjoy Thanksgiving.

God and nature willing, I’ll awake the next day ready to love my family, continue the fight to defeat HD, and dream of a day when a cure frees me to assist people less fortunate.

Happy Thanksgiving! And the best of health for you and yours.

Roche Phase 3 clinical trial for Huntington’s disease gene-silencing drug to enroll volunteers in early 2019

The major drug company Roche expects to start enrolling subjects worldwide (including the U.S.) in early 2019 in its historic Phase 3 clinical trial of RG6042, a gene-silencing drug aimed at slowing, halting, and perhaps even reversing the symptoms of Huntington’s disease.

Roche made the announcement today at the bi-annual plenary meeting of the European Huntington’s Disease Network in Vienna, Austria, and issued a statement to the global HD community providing details (click here for the statement).

Designed by Roche partner Ionis Pharmaceuticals, Inc., and previously known as IONIS-HTT_Rx, RG6042 demonstrated impressive results in the Phase 1/2a trial completed by Ionis in December 2017.

On March 1, at CHDI Foundation's 13th Annual Huntington’s Disease Therapeutics Conference, researchers revealed that RG6042 caused Phase 1/2a trial volunteers to experience a drop of 40 to 60 percent in the harmful mutant huntingtin protein in their cerebral spinal fluid (CSF). According to the researchers, projecting from tests in animals, that corresponds to as much as an 85 percent decrease in the cortex of the brain. However, this trial did not measure actual efficacy – only safety and tolerability. (Click here to read more.)

Scientists have identified mutant huntingtin protein, resulting from a defective huntingtin gene inherited by HD patients and carried by presymptomatic individuals like me, as a principal cause of HD.

Because of the solid Phase 1/2a results, Roche has taken the unusual step of skipping a Phase 2 trial (testing efficacy for the first time) and going directly to a robust Phase 3, where researchers hope to test efficacy in 660 volunteers over 25 months at 80 to 90 sites in approximately 15 countries, to be announced gradually in the coming months. Phase 1/2a involved only 46 individuals, who received the drug over just three months at nine sites in Canada, Germany, and the United Kingdom.

In a detailed interview at the CHDI meeting, Roche officials confirmed that U.S. sites would take part in Phase 3 (click here to read more).  

GENERATION HD1: can it stop or slow HD?

“Following the completion of the Phase I/IIa first-in-human study of RG6042 in December, there are several important questions that still need to be answered before this investigational medicine can potentially be approved by Health Authorities in countries around the world,” said today’s Roche statement, signed by Mai-Lise Nguyen, the patient partnership director for the firm’s HD program.

Roche has named the study GENERATION HD1. 

As outlined by Nguyen, GENERATION HD1 will gauge the effects of reducing mutant huntingtin and whether RG6042 can “slow or stop the progression of HD.” It will also further examine the drug’s safety in a larger group of people over more time.

Members of the Roche HD clinical trial team watch the presentation of the RG6042 Phase 1/2a results at the 13th Annual HD Therapeutics Conference in Palm Springs, CA, March 1, 2018. From left to right, Scott Schobel, M.D., M.S., clinical science leader of product development; Lauren Boak, Ph.D., global development team leader; Erik Lundgren, lifecycle leader of the HD program; and Mai-Lise Nguyen, patient partner director (photo by Gene Veritas).

The trial will also study whether less than a monthly dose, which was used in Phase 1/2a, can prove effective. One third of participants will receive monthly doses of 120 mg, one third a bi-monthly dose of 120 mg, and another third a placebo dose monthly. As in the Phase 1/2a trial, participants will receive the drug via a lumbar puncture (a so-called intrathecal injection). 

To assure objectivity, the study will be “double-blinded” – neither the participants nor the researchers or site staff will know which dosage is administered. To reinforce objectivity, even the bi-monthly recipients (who won’t know they’re in this group) will take part monthly; they'll get the placebo every other month. Site information will be posted on the site www.HDTrialFinder.org.

Today’s statement underscored the “urgency” felt by Roche to conduct GENERATION HD1 but pointed out that not all patients and research clinics will be able to participate. “Please understand the studies are designed to provide Authorities with the required data so that the benefit-risk of RG6042 can be determined as quickly as possible,” it stated.

For now, because Roche needs to demonstrate the efficacy and safety of RG6042, the firm will offer access to the drug only through participation in clinical trials. This means patients cannot make early access (prior to regulatory approval), so-called compassionate use, or “right to try” requests.

At this time, presymptomatic gene carriers and juvenile HD patients are ineligible for GENERATION HD1.

Additional studies

In addition, Roche will conduct a second, 15-month observational study – without a drug – called The HD Natural History Study. Starting towards the end of this year, it will gauge the natural progression of the disease in up to 100 participants with early-stage HD at up to 17 sites in Canada, Germany, the United Kingdom, and the U.S.

By seeking to deepen understanding of the role of the mutant huntingtin protein in HD, the Natural History Study will provide context for GENERATION HD1. Participants will undergo four lumbar punctures, plus MRI scans, blood tests, and neurological examinations. Like the volunteers in GENERATION HD1, they will use digital monitoring devices.

Meanwhile, all 46 participants in the Phase I/IIa study continue to receive RG6042 as part of an “open-label extension” study run by Ionis to assess the safety and tolerability of longer use of the drug. Those who got placebo originally now get the medicine.

Fast-tracking drug evaluation

The EHDN update comes in the wake of an August 2 announcement by Ionis and Roche that RG6042 received “PRIME” (PRIority MEdicine) status from the European Medicines Agency (EMA), a regulatory body similar to the U.S. Food and Drug Administration (FDA).

“We are very pleased that the European Medicines Agency has granted PRIME designation for RG6042, as there is an urgent medical need to find treatment options for families affected by Huntington’s disease,” Sandra Horning, M.D., Roche’s chief medical officer and head of global product development, stated in a press release.

According to the EMA, firms benefitting from PRIME “can expect to be eligible for accelerated assessment” in the drug approval process, reducing the standard timeframe of 210 days to 150 days.

A major step, but not the last

In March, after witnessing the revelation that RG6042 successfully lowered mutant huntingtin protein in the CSF, I wrote: “It’s the best news the HD community has received since the publication of the research confirming the discovery of the gene 25 years ago this month. As scientists have observed, it’s also a major step for disease and drug research in general.”

The August 24 issue of the magazine Science published a balanced article about the Ionis-Roche clinical trials titled “Daring to Hope,” including the struggles of Canadian woman and Phase 1/2a trial and open-label extension participant Michelle Dardengo. She describes some improvements in her symptoms – although doctors caution that her situation is merely anecdotal and not proof of actual drug effectiveness.

Michelle’s 27-year-old son Joel has also tested positive for HD. He was more skeptical about her apparent improvement.

“I do wish for the best,” Joel states in the article. “At the same time, I do prepare for the worst.”

Like all of the HD community, Michelle, Joel, and I must wait for the completion of GENERATION HD1 early in the next decade to see if RG6042 can help save us from HD.

For discussion of the Roche announcement at the EHDN meeting, see the HDBuzz Twitter feed for September 16, 2018.

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

With more Huntington’s disease clinical trials, volunteers need help with comparison shopping

After learning last month that some researchers believe the drug under study in the SIGNAL clinical trial might slow the progression of Huntington's disease, I was excited about the possibility of participating.

SIGNAL is open to asymptomatic carriers of the HD gene like me. I tested positive in 1999, and my mother succumbed to the disease in 2006.

This is a huge decision, so I have been weighing the risks and benefits with my wife and members of the HD community.

After posting an article about SIGNAL on November 1, I started to waver about whether I should take part in the trial of VX15/2503, a monoclonal antibody made by the small Rochester, NY-based biotech company Vaccinex.

I wondered: how safe is the drug? Why hadn’t I heard about SIGNAL before? With the trial based on just one recent paper about a test of the drug in transgenic HD mice, and with other trials typically based on more tests, I wanted to know more about the science behind it.

I contacted a number of people in the HD research community. Privately I received assurances about the safety of VX15/2503 and its potential for alleviating HD – but also recommendations against participation. One obvious major concern is that the compound is non-HD-specific, in contrast with the one currently under study in the historic Isis Pharmaceuticals, Inc., gene-silencing trial.

In a future article, I hope to interview Vaccinex scientists about why they think their compound can help HD patients and presymptomatic individuals like me.

Learning the background of clinical trials and deciding on participation can be challenging. In addition to consulting with physicians and clinical trial administrators, HD people and their families could benefit from better information about clinical trials. In this article I explore these issues and one (albeit partial) solution: the idea of a patient/caregiver advisory council to provide information and advice about HD trials.

No ranking system

Each year, more HD trials take place, each with unique drug mechanisms and participant selection criteria. Each volunteer must ask: which is best for me?

It’s possible that a good drug could be left out of the race because of the increase in the number of trials: the patient pool might be too small to furnish enough volunteers for every trial.

The Huntington’s Disease Society of America (HDSA), the leading patient organization in the U.S., recently launched an online search tool, HDTrialfinder. It’s a “clinical trial matching service” that provides information similar to that found on at Clinicaltrials.gov, but in a somewhat clearer format. It has HD-specific search tools and provides the opportunity to receive updates via email. It lists current HD trials.

However, it does not rank or recommend trials.

“HDSA does not endorse any interventional HD drug studies, but we do encourage individuals to talk with their physicians about the opportunities to participate in all types of clinical research that can help lead to treatments for HD,” said George Yohrling, Ph.D., HDSA’s Director of Medical & Scientific Affairs. “Additionally, we strongly recommend that patients do their own due diligence to better understand exactly what their involvement in a study would mean to them and their families.”

HDBuzz.net, podcasts such as Help4HD’s “The HD View,” and other online sources also provide easy-to-understand information about HD research and HD clinical trials, but don’t offer recommendations or rankings.

Cautions about new experimental drugs

To get a broader understanding of clinical trial planning and HD families’ part in the process, I conducted a 90-minute phone interview with LaVonne Goodman, M.D., on November 16. The founder of Huntington’s Disease Drug Works and physician to many HD patients, Dr. Goodman has provided the HD community with a constructively critical view of the process and its many related issues.

Dr. Goodman began with some general observations about clinical trials and volunteering for them.

“In general, I have problems with giving an experimental drug with unknown risks to individuals who have minor or no symptoms of HD,” she said. “Though it may sound maternalistic, it is my bias that, if you have a clinical trial for this group of people who aren’t very sick at all clinically, then a new experimental drug should not be tried in them first. The risks are unknown, and that’s different than giving the drug to a symptomatic individual who is already sick, because they have more at stake and are willing to take a greater risk.”

LaVonne Goodman, M.D. (photo by Gene Veritas)

Two key questions about trials

“We trust our beloved doctors,” Dr. Goodman continued. “When they do a clinical trial, we may assume incorrectly that they know all the background. But they aren’t given all the (scientific) background.”

Dr. Goodman referred to an article she posted in March about the drug laquinimod, currently under study in a clinical trial sponsored by the Israel-based pharmaceutical firm Teva. (Laquinimod has already undergone testing for multiple sclerosis and shown various benefits for the brain, making it a good compound, with fairly well known risks, for an HD trial.)

In the article, she noted that prominent cancer researcher and author Siddhartha Mukherjee, M.D., Ph.D., has suggested that patients ask two “vital” questions about clinical trials: “Why is the trial being done?[...] What were the data that led to the clinical trial in the first place?”

“This is particularly important as our clinical trials become more complicated, and several are recruiting concurrently,” Dr. Goodman wrote. “This information should be provided to the community in a format that is easily assessable and in language that potential participants can understand for every new trial.”

She warned: “Can sponsors or investigators expect participants to sign up when the rationale for testing the drug isn’t more available?”

A clinical trial rating scale

Dr. Goodman proposed that a rating scale – done with feedback from HD families – could help patients select trials and assure that the most important trials secure enough volunteers.

“I think there are some broad recommendations that could be done with a rating scale,” she said, adding that it could be created with an “independent” group made of patient advocates and representatives from the Huntington Study Group (administrator of SIGNAL and other HD trials), HDSA, and other organizations.

“Patients’ families are not part of the discussion when it comes to HD clinical trials,” Dr. Goodman said. “There are groups like cystic fibrosis and breast cancer where there is precedent for this. I think it would be helpful to our particularly vulnerable community.”

Dr. Goodman believes the establishment of such a council may be a “moral obligation” to HD families.

Indeed, behind the scenes, some HD researchers, advocates, and others in the community have begun discussing the formation of a patient/caregiver advisory council to furnish input to HSG and other groups involved in clinical trials regarding clinical trial design and selection. Such an initiative could include a rating scale.

However, a rating scale must be built in a positive and efficient way that would “not push drug company sponsors away,” Dr. Goodman added.

Dr. Goodman pointed out that drug companies may trial a new drug in HD that was originally developed for another disease.  This is true for drugs in the LEGATO (laquinimod), Amaryllis, and SIGNAL trials.  It remains to be seen whether this is a good approach for HD, she said.

Furthermore, HDSA Centers of Excellence and other HD clinics need greater funding to increase access to care and therefore the number of people potentially interested in clinical trials, she said. At best, just a quarter of individuals with HD are seen by research center neurologists. High costs prevent more HD people from seeing these neurologists, a situation unlikely if the U.S. had a national healthcare system, she noted.

The FDA and momentum for a council

Momentum for patient/caregiver advisory councils for HD and other diseases is building in the wake of the recent and historic set of “patient-focused drug development” hearings held by the U.S. Food and Drug Administration (FDA), including the September 22 meeting on Huntington’s (click here to read more).

In the words of one informed observer, the FDA is “not just doing this for show.” The agency will likely start requiring drug companies to include patients’ perspective in clinical trial design.

Despite its duty to safeguard the public, the FDA itself also does not rate or recommend drugs, although it does carefully examine the outcome of a clinical trial before approving a drug for the market.

Likewise, the FDA is concerned primarily about toxicity when allowing a company to go forward with a Phase I or II clinical trial (when safety is the primary concern). For instance, the agency does not look at whether a drug for HD actually gets into the brain, Dr. Goodman said.

“Their primary objective is to not let something that appears too unsafe get into a clinical trial,” she observed. “They don’t discourage drug companies from testing drugs. On the contrary, they want drugs to be tested.”

Comparing trials

We can imagine the idea of an HD clinical trial rating scale overseen by a patient/caregiver advisory council as giving us the same power people have when doing comparison shopping at sites such as Consumer Reports or CNET.com.

We need information that is succinct but relevant, scientifically rigorous but understandable.

We also need the capability to compare the different trials. For those council members who ask, the trial sponsors could furnish full scientific data.

In effect, the HD community has often acted as its own clinical trial guide.

The decision to participate in a clinical trial is ultimately a personal one best made in consultation with a physician.

Having the additional assistance of a rating scale can facilitate the process and potentially speed the search for effective treatments.

Might I finally take part in a Huntington’s disease clinical trial? An update on the latest research

In the 20 years of my family’s fight against Huntington’s disease – we discovered my mom had HD the day after Christmas of 1995 – I felt this past week for the first time that I might have a chance to avoid its inevitable, mind-destroying symptoms.

On October 26, I learned about a new clinical trial aimed at rescuing brain cells from the degeneration caused by Huntington’s.

Called “SIGNAL” (alternatively, VX15/2503 Treatment for Huntington’s Disease), the trial will include asymptomatic carriers of the HD gene like me who are close to predicted age of onset. Made by the Rochester, NY-based biotech company Vaccinex, VX15/2503 is a monoclonal antibody, a type of molecule essential in molecular biological research.

Monoclonal antibodies are used in various forms by companies such as Vaccinex to treat an increasing number of conditions such as cancer. Vaccinex is also enrolling volunteers in a VX15/2503 trial for multiple sclerosis. Vaccinex believes the very same compound might help alleviate a host of other neurodegenerative diseases.

“The thought is that if we could give this drug early enough we can actually slow the progression of Huntington’s, and that’s really exciting,” said Jody Corey-Bloom, M.D., Ph.D., the director of the Huntington’s Disease Society of America Center of Excellence for Family Services and Research at the University of California, San Diego. She spoke to more than 50 people attending her annual HD research update presentation at the San Diego support group on October 26.

Jody Corey-Bloom, M.D., Ph.D. (photo by Gene Veritas)

Aiming to halt progression, delay onset

Dr. Corey-Bloom, who's provided research updates to the support group since 2005, kicked off this year’s presentation with a review of the historic news on October 19 that HD patients in England had received the first dosing of an Isis Pharmaceuticals drug, ISIS-HTT_Rx, aimed at stopping the disease at its genetic roots. ISIS-HTT_Rx is an antisense oligonucleotide (ASO), an artificial strand of DNA (click here to read more).

SIGNAL, initiated in June, is the “biggest” news on the HD clinical trial field scene since the development of ASOs for use in HD, Dr. Corey-Bloom said. SIGNAL marks the first ever use of a monoclonal antibody in an HD clinical trial, she noted.

“So we’re not just treating motor signs,” she said of SIGNAL. “We’re actually trying to slow the progression. And the reason is that this also belongs to a class of drugs that blocks inflammation in the brain in animal models. And so the hope is that we could either delay the onset or slow the progression.”

VX15/2503 would help HD patients by reducing inflammation in the brain. Scientists primarily from the lab of world-renowned HD expert Michael Hayden, M.D., Ph.D., in collaboration with Vaccinex researchers, published a breakthrough study in April in the journal Neurobiology of Disease demonstrating how the use of a monoclonal antibody restored health in HD mice.

Vaccinex is one of a growing number of biotech and pharmaceutical companies that have delved into the search for HD treatments as research has greatly expanded.

As the scientist-written HD research site HDBuzz noted last February, other investigators are seeking ways to use other antibodies in the quest for treatments.

You can watch Dr. Corey-Bloom’s research update, which includes details on numerous other hopeful projects, in the video below.

Update on Huntington's Disease Research 2015: A Presentation by Dr. Jody Corey-Bloom from Gene Veritas on Vimeo.

Including presymptomatic volunteers

HD clinical trials have rarely included presymptomatic people because of ethical concerns and the inability of science to measure a meaningful effect.

However, SIGNAL includes presymptomatic individuals for several reasons, in part because ways of detecting and interpreting the symptoms have become ever more effective, Dr. Corey-Bloom explained.

“You have to be gene-positive, but you don’t even have to have a diagnosis, because they believe that the drug itself is not going to hurt you,” she said, adding that the current stage of the SIGNAL trial (Phase II) is primarily to confirm its safety. (Later a Phase III would test the drug’s efficacy.)

SIGNAL will evaluate changes in participants’ brains using “very unique, very high-level, high-quality imaging,” she said. “They’re doing very special PET studies, and they’re also doing very special MRI studies, DTI, diffusion tensor imaging, and so just a lot of very, very special techniques that are being orchestrated by the Massachusetts General Hospital and [researcher] Diana Rosas.”

Measuring the effects

One attendee asked specifically how a presymptomatic individual would know whether onset had been delayed.

“I think the imaging data is going to be really compelling,” Dr. Corey-Bloom said, noting that previous research has abundantly demonstrated changes in the brain a decade or more before onset, as well as precise measurements in those changes over time. “I think they’re going to be able to tell that it isn’t declining the way people who aren’t being treated is declining.[…] If you’re in the early stages and stay there, that would be pretty impressive, too.”

Involving 36 volunteers at 13 sites across the country, SIGNAL will deliver VX15/2503 intravenously once per month over twelve months in one group and over 18 months in a second group. Dr. Corey-Bloom, whose Center of Excellence enrolled the first patient in SIGNA, said that each infusion would last about an hour. (Click here for the official details of the trial, which will be administered by the Huntington Study Group [HSG]). The HSG just completed its 2015 meeting, held October 21-24 in Tampa, FL.

Further information about SIGNAL in the San Diego region is available at 858-246-1254.

Confidence, but….

I will call that number very soon to learn more about my eligibility and the risks involved.

I tested positive for HD in 1999, and my mother died of the disorder in 2006 at the age of 68 after a two-decade battle. I’m almost 56, a stage where my mother already had involuntary movements and suffered from cognitive loss.

After attending the HD support group and seeing symptomatic friends, I’m always worried about onset.

Dr. Corey-Bloom’s recap of the good news about the long-awaited Isis clinical trial left  me with a feeling of confidence that someday we will defeat HD – but perhaps not in time to stop my onset. The Isis trial does not include presymptomatic individuals, and, even if successful, it could take five, ten, perhaps even 20 years for the approach to have a significant impact on the disease.

Wishing for a ‘normal’ life

However, after hearing about SIGNAL for the first time, a flood of new emotions began to pour over me.

I immediately felt hope for my friend Sharon Shaffer, my HD sister, and other HD-affected individuals in the audience.

Sharon Shaffer and mother Fran Walker (photo by Gene Veritas)

I awoke at 3:45 the next morning full of energy. Unable to sleep again, I worked on processing the video of Dr. Corey-Bloom’s talk.

“My 20th year attending support group – what a difference!” I wrote in my notes. “Treatments and trials, people asking questions about real scenarios, not just long-off hypotheses. PLUS: I learned of a trial that I can maybe take part in and see symptoms prevented. What if my career can be ‘normal’ and my life ‘normal’?”

I’ve hardly ever had such positive thoughts, although I recognize that I am extremely lucky to have remained asymptomatic this long.

Risks vs. benefits

My wife, who has seen so many of her own plans dashed because of HD, was pleased to hear about SIGNAL.

She hopes every day for a treatment to save me, as well as others, from the devastation she witnessed in my mother.

As I gather more information in the coming weeks, and if I am eligible to participate in SIGNAL, I will weigh risks and benefits with her, my physicians, and members of the HD community.

My immediate concerns: could VX15/2503 cause harmful side effects or even trigger HD? Would participation somehow prevent me from taking part in other trials in the future?

‘Unimaginable scenarios’

Regardless of my participation, I will follow this project with keen interest – as surely will the rest of the HD community.

As with the Isis compound, there is no guarantee VX15/2503 will work.

However, it is yet another shot on goal in the search for effective treatments. The more shots, the better the chance of success.

The HD community can now envision scenarios unimaginable 20 years ago. That's significant progress.

At key FDA meeting, Huntington's disease community insists on faster search for treatments

The Huntington’s disease community sent a powerful message to the U.S. Food and Drug Administration (FDA) at the September 22 meeting on HD patient-focused drug development: the agency must do its utmost to facilitate clinical trials and speed the search for effective treatments.

“We discovered the gene – we don’t have a cure,” declared Nancy Wexler, Ph.D., the famed researcher who initiated the search for the huntingtin gene while watching her mother suffer and ultimately die from HD. She addressed the panel of ten FDA officials and audience of some 200 HD family members and advocates at the agency’s headquarters in Silver Spring, MD. “We did that [discovery] in 1993.”

Along with Wexler, two panels of HD family members selected by the FDA to make presentations about the disease and current lack of effective remedies, as well as other participants in the unusually large meeting, described HD’s cruel devastation and the exhausting burden for caregivers.

The Huntington’s Disease Society of America (HDSA), which advocated for the meeting under the new requirements for patient feedback established by Congress for the FDA, sought to provide the FDA with a more tangible and comprehensive view of HD’s reality, all too familiar to affected families.

The FDA doesn’t conduct drug research, but its regulators must approve all clinical trials and new drugs in the U.S.

The plethora of symptoms

Many presenters and audience commenters emphasized the plethora of cognitive, behavioral, and other symptoms involved in HD in addition to chorea, the involuntary movements traditionally but erroneously labeled the key diagnostic signifier of the disease.

“I have all of the symptoms that have nothing to do with chorea,” stated presenter Julie Rosling, 72, of Orange, CA. Forced to retire some ten years ago from her pharmacist job, Julie participated on the five-person panel about the daily impact of HD.

I first met Julie almost 20 years ago in San Diego at the local HD support group, several years before I tested positive for the genetic defect that causes the disease. At most meetings the group had three breakouts: for the affected, caregivers, and untested individuals and asymptomatic gene carriers. Julie and I participated in this last breakout group. Sharing our most intimate fears about HD, we became friends.

I hadn’t seen Julie in a few years. I had long admired her intelligence, profound knowledge of HD science, and healthy lifestyle. My wife and I viewed Julie as a model for avoiding HD and, once her symptoms started, for living with the disease. She has late-onset HD, in contrast with most patients, who experience onset between 35 and 55.

From left to right, Frances Saldaña, Julie Rosling, Reed Rosling, and Gene Veritas (aka Kenneth P. Serbin) (photo courtesy of Frances)

‘I can’t play Chopin anymore’

At the FDA meeting, I was shocked and saddened to see how the disease had, as Julie put it in her presentation, greatly affected her demeanor.

“There are so many different types of symptoms,” Julie said, adding that HD must no longer be seen as just a brain disease. She described how she can no longer drive, suffers from insomnia and gastrointestinal difficulties, and fears choking, a common problem with HD.

“I fall all the time when I go up and down the stairs,” she continued. “The thing that’s the most important […] is that my symptoms are affecting every system in my body.”

Sadly, HD has robbed Julie of many favorite activities. Each December, Julie, a painter, sent out exquisitely designed holiday cards. Several years ago, she wrote in her holiday card that she could no longer paint the cover for her cards.

Those beautiful cards always brought me a glow of hope. I have missed them.

“I can’t play Chopin on the piano anymore,” Julie said at the FDA. “I can’t walk to the corner and back.”

HD has hampered her social interaction, too, because of her slurred speech.

“My symptoms have never gotten better,” Julie concluded. “They get worse every single day. I am a living example of what this disease is all about.”

Once again, I had looked into the genetic mirror and viewed my own highly probable future decline.

You can watch Julie’s presentation in the video below. To watch other presentations, click here to visit my video album of the meeting.

'I Can't Play Chopin on the Piano Anymore' from Gene Veritas on Vimeo.

FDA ‘blown away’ by turnout

“I think it was a very successful day,” said HDSA CEO Louise Vetter in an interview with me shortly after the meeting. “I’m really pleased with how full the room was, not only from the patient and community side, but also the FDA. They had a full docket of folks who wanted to be in the meeting to listen to the HD community.[…] There were more FDA staff in the room than is typical for a public hearing.”

The FDA’s level of interest demonstrated its “commitment to paving the way for new therapies for HD,” Vetter added. The FDA was “impressed” with the “urgency” and “commitment” of the HD community.

“The FDA was blown away,” she said, adding that the agency at the last minute had to set up a room “three times larger than what they planned.”

FDA regulators at the Public Meeting on HD Patient-Focused Drug Development (photo by Gene Veritas)

Several dozen HD community members participated in the hearing via webcast. In addition, representatives attended from CHDI Foundation, Inc., the nonprofit virtual biotech focused exclusively on the search for HD therapies, and the pharmaceutical industry.

The HD hearing took place in the morning, followed by a Parkinson’s disease meeting in the afternoon. The FDA had initially combined HD and Parkinson’s concerns into a single event, but HDSA convinced the agency to divide the meeting because of significant differences in the two conditions and the different treatment approaches, Vetter explained.

“We had more people than Parkinson’s had planned, and given the difference in prevalence, the FDA really took notice,” she said.

“I’m just so pleased with how many caregivers and family members really came prepared to succinctly share their stories and open up about the impact of the disease and their hopes and wishes. I know that the FDA heard that.”

FDA regulators Leonard Kapcala, M.D. (above) and Peter Como, Ph.D., and Lei Xu, M.D., Ph.D. (below) watch presentations by HD advocates (photos by Gene Veritas)

Still time to submit comments

HDSA requested the hearing as soon as the Congressional mandate for patient-focused feedback to the FDA went into effect in 2012. HDSA told the FDA that it could learn much from HD as a genetic disease, given a clearly identified gene and a community of affected families with a serious need for treatments, including preventative remedies for presymptomatic gene carriers, Vetter noted. HDSA also said HD could be a case study for understanding and treating other diseases.

In addition, HDSA will submit to the FDA survey responses from 3,600 HD-affected individuals and family members regarding the impact of symptoms and desired treatments, Vetter noted in her public comments at the hearing.

The public can provide further feedback to the FDA until November 23, 2015, by clicking here.

Several months after the public comment period closes, the FDA will complete a “Voice of the Patient” report on HD, Vetter told me. HDSA will carefully review the report and provide feedback.

You can watch Vetter make her public comments in the video below.

HDSA CEO tells FDA: Study the Broad Feedback from from Gene Veritas on Vimeo.

Advocating for the presymptomatic

During my brief remarks (audience members got only two minutes per commentary), I told of my mother’s demise, our daughter’s gene-negative status after testing in the womb, and my luck at remaining presymptomatic at 55, well beyond the point where my mother experienced many symptoms.

“I would like to see a medication that prevents me from ever getting any kind of symptoms,” I said. “There’s got to be a really open dialogue with the scientists on the new areas such as gene-silencing.”

I referred to the disappointment among HD advocates that the first gene-silencing clinical trial for HD, by the Carlsbad, CA-based Isis Pharmaceuticals, Inc., is happening outside the United States. (Phase I of the trial started in July in Europe and Canada; click here to read more.) I remarked that some drug company executives think the FDA too inflexible regarding new approaches. I urged the regulators to consider the new biomarkers (signs of disease and drug efficacy) scientists are seeking to measure in the blood, cerebrospinal fluid, and brain measured with new techniques.

Many presymptomatic people don’t get tested “because of the immense fear of the disease and the fact that there are no treatments,” I added during the final round of comments. “There’s also associated with genetic testing and getting your results a lot of suicidal tendencies.”

I recalled my suicidal fantasies from the early years of my family’s struggle with HD, when I saw my mother declining. Those ended after the birth of my daughter, I added.

“The presymptomatic population out there really needs to be part of the conversation,” I urged.

The urgent need for treatments

The FDA regulators, unsurprisingly, offered little comment on the proceedings; they wanted to listen and learn.

After returning home, on September 25 I requested an interview to follow up on the above-mentioned points, and more, including calls from families with juvenile HD patients for JHD-specific approaches to clinical trials and treatments. I have not yet received a response, but will write an update when I learn more.

However, HDSA CEO Vetter recalled for me the nub of her conversation with William Dunn, M.D., a neurologist and the FDA’s director of the Division of Neurology Products, immediately after the meeting. Dr. Dunn had welcomed the participants at the meeting’s start.

“He’s very committed to this,” Vetter said, referring to the search for HD treatments. “He was very impressed, very grateful for the input of the families, and very committed to making sure that, as therapies move forward to FDA consideration, they will be efficient in their review, that the FDA’s not sitting on anything. The last thing they want to do is be accused of keeping something meaningful out of the hands of families. They’re very committed to being very expeditious and thorough.”

Along with many fellow HD family members, I believe that the FDA gained a clearer understanding of our community’s suffering and the urgent need for treatments.

* * *

For the FDA’s recording of the meeting, click here. Be sure to visit my video album for other perspectives expressed at the hearing. For additional photos from the meeting, click here.

For the perspective of Parkinson’s specialist Jeanne Loring, Ph.D., click here.

(Note: HDSA paid for my travel to Silver Spring and a night of lodging. The views expressed in this article are wholly mine.)

HD advocate Katie Moser (left), HDSA CEO Louise Vetter, and advocate Emma Burris (photo by Gene Veritas)