LaVonne Goodman, M.D. (photo by Gene Veritas)
Tuesday, November 24, 2015
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)
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.”
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.
Sunday, November 01, 2015
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-HTTRx, aimed at stopping the disease at its genetic roots. ISIS-HTTRx 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.
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?
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.
Monday, October 19, 2015
Huntington’s disease patients get first dosing in historic Isis Pharmaceuticals’ gene-silencing drug trial
Huntington’s disease patients in England have received the first dosing of an Isis Pharmaceuticals drug, ISIS-HTTRx, aimed at stopping the disease at its genetic roots.
The patients displayed no immediate complications. This so far confirms expectations that the gene-silencing drug would be safe to use, although clinical trial administrators will continue to make critical observations in the coming months. Other dosings will occur. The drug’s efficacy will not be analyzed until later stages of the trial.
An announcement came October 19 that a small number of Phase I clinical trial participants at University College London (UCL), the lead site for study, had received injections via spinal cord of the Isis compound, according to a UCL news release.
“It's the beginning of quite an important journey in Huntington's disease,” Sarah Tabrizi, Ph.D., the director of UCL’s Huntington's Disease Centre and the global chief clinical investigator for the trial, told the BBC. “It is clearly very early but this is a step forward.
“The preclinical work shows that if you lower production of the mutant protein then animals recover a large amount of motor function. Huntington's is a really terrible disease that blights families. I know a mother whose husband and three children were affected. This would have a massive impact [if it works].”
Sarah Tabrizi, Ph.D. (photo from University College London website)
Slowing or preventing the disease
The news comes just three months after Isis announced the official start of the trial, the first time HD patients are receiving a substance aimed to attack the genetic causes of the disease. Isis has partnered with the Swiss-based pharmaceutical giant Roche to facilitate the clinical trial and, if it’s successful, the marketing of the drug.
Isis officials were unavailable for comment on October 19 but the main scientist spearheading the development of ISIS-HTTRx, which signifies a medication for HD, commented in the UCL release.
“We designed ISIS-HTTRx to target the huntingtin gene and reduce the production of huntingtin protein, which is the known cause of the disease,” stated Frank Bennett, Ph.D., the Isis senior vice president for research. “This approach has the potential to prevent or slow the progression of this disease. If this first-in-human trial proves the drug is safe, we look forward to continuing our successful partnership with Roche to bring the drug to market.”
Dr. Bennett has previously described the drug, scientifically known as an antisense oligonucleotide (oligo), as a “laser-guided missile” targeting a “specific messenger RNA that causes a particular disease and kill it or take it out of the body so that you don’t produce that messenger RNA.”
Isis announced the details of the trial in August 2014 (click here to read more).
Frank Bennett, Ph.D., senior vice president for research at Isis Pharmaceuticals (photo by Dr. Ed Wild)
Safety and tolerability first
The Phase I trial involves patients at UCL and also at various sites in Canada and Germany. Across all sites, a total of about 36 patients will take part. Phase I trials focus primarily on the safety and tolerability of a drug. The study will also help determine the frequency and size of dosages for eventual Phase II and Phase III trials, which measure efficacy.
All of the volunteers have early stage HD. Because of the use of spinal taps to administer the drug and the highly experimental nature of the oligos, no non-HD-affected individuals are taking part as controls.
No announcements have yet been made about dosing of patients in Canada and Germany.
According to the UCL release, the ISIS-HTTRx is taking place in the new Leonard Wolfson Experimental Neurology Centre, a custom-built facility designed to accelerate innovative treatments for neurodegenerative diseases.
“The administration of the first doses of ISIS-HTTRx marks the Centre's first use as a phase 1 'first into human' trial facility, as well as the first time that an experimental drug has been given by spinal injection in the 156-year history of the National Hospital for Neurology and Neurosurgery, part of University College London Hospitals (UCLH) NHS Foundation Trust,” the release stated.
“The first volunteers have been treated without any immediate complications,” the scientist-written HD research site HDBuzz observed. “The next year or so will be a period of intense study of these trial volunteers to make sure that they don’t have unexpected complications from the treatment. They’ll also be examined for a range of measures of whether or not the drug is working, which will provide critical information for planning future HD gene silencing studies.”
Depending on the pace of recruitment, Phase I most likely will end in 2017. If Phase I is successful, Phase II could follow no sooner than nine months later. All three phases of a clinical trial program typically take at least five years.
Historically, only ten percent of clinical trials ever result in a marketable drug.
Regardless, the HD community has crossed a significant threshold. Science has yet to produce an effective treatment for HD, as well as for Alzheimer’s, Parkinson’s, and other neurological disorders. HD could be the first.
Hope is palpable.
As a carrier of the deadly HD gene who lost his mother to the disease in 2006 and has tracked the Isis project since 2007, I am thrilled that our fellow HD community members have successfully made the first step in this historic clinical trial. They deserve our enthusiastic applause for volunteering.
(Disclosure: I hold a symbolic amount of Isis shares.)
Tuesday, October 13, 2015
At-risk Angels pitcher Joe Smith at Huntington’s fundraiser: ‘I’d give every dime I have for a cure’
No one person is the face of Huntington’s disease the way ALS is associated with Lou Gehrig or Parkinson’s disease is linked with Michael J. Fox. But HD touches many lives, including some we know from major league sports.
Choking back tears, 31-year-old Los Angeles Angels baseball pitcher Joe Smith remembered the phone call three years ago from his father back in his native Ohio that changed his life forever: his mother had been diagnosed with Huntington’s disease.
“Unfortunately, I got a call driving home from our spring training site in Goodyear, Arizona, from my dad,” Joe told an audience of over 400 people at a San Diego fundraiser on October 10. “He told me: mom had HD.”
Then Joe recalled when his mother Lee came on the phone on that day in February 2012, not long after she had received her genetic test results confirming she had HD.
“I’ll never forget the sound of her voice,” he said. “It was just empty. It was the worst. I never heard anything like it. That stayed with me for a long time, that sound, when she said, ‘Hi, Joseph,’ but the way she said it […] was different. And it hurt. It still does, obviously. This time, when she got the news, I still didn’t know a whole lot about HD. But obviously, when you get off the phone with the parents and got a 30-minute drive, there’s a lot of thinking that goes on.”
He’s done a lot of thinking – and action – since then.
For his efforts to raise awareness and funds for the HD cause, Joe received the Guthrie Award of the Huntington’s Disease Society of America (HDSA) at the San Diego chapter’s 15th Annual Celebration of Hope Gala, held this year at the spectacular coastal residence of Craig and Rebecca Irving. Craig is a businessman and philanthropist.
Above, Joe Smith and mother Lee (photo by Gene Veritas, aka Kenneth P. Serbin). Below, Celebration of Hope Gala attendees mingling before the start of dinner and the formal program (photo by Mike Nowak).
Staring HD in the face
Joe remembered his family’s four-hour drives from southern Ohio to Cleveland to visit Lee’s mother, who, the family knew, suffered from HD. Seeing his grandmother’s progressively worsening symptoms at each visit left Joe sad and concerned as a child and teenager.
“I think that’s the scariest part,” Joe continued. “It’s one thing, I think, to go through life, or to have something that not necessarily you don’t know about, but […] my mom took care of my grandma, she went to doctor visits with my grandma, she was on the phone all the time with my grandma.
“When you know the road you’re heading down, and right now there’s nothing that you can do about it, you’re just going. You’re hoping there’s light. You got hope. You got faith. But at the end of the day, right now, there’s no cure.”
Lee did not speak at the gala but talked about her symptoms in a brief video shown to the audience.
“She stares it right in the face every day,” Joe said, referring several times to his mother’s fortitude.
Joe ended his speech with a call to boost fundraising for HD research.
“I’d give every dime I have if they had a cure today,” he declared.
You can watch Joe’s speech in the video below. View other videos of the event by clicking here.
Los Angeles Angels' Joe Smith: 'I'd Give Every Dime I Have for a Cure for Huntington's Disease' from Gene Veritas on Vimeo.
Taking public action
As the children of an HD-affected parent, both Joe and his 29-year-old sister Megan Nein have a 50-50 chance of inheriting the genetic defect.
Joe has previously talked to the press about his fears of living at risk.
“My sister has three kids and she hasn't been tested,” Joe said last March. “I got married recently, and I'll get tested before we have kids.”
He didn’t speak directly about his fears at the gala, but they were palpable throughout his speech.
Both Joe's and HDSA CEO Louise Vetter’s comments once again demonstrated how HD can devastate the extended family because of its genetic cause and difficult caregiving burden.
“It’s not easy to come out and say you’re from an HD family,” Vetter said in introducing Joe. “If one of your parents has it, you don’t know if you have it or not. So it takes a lot of courage to face your future.”
Recalling Woody Guthrie’s widow Marjorie’s founding of HDSA in 1967, the organization recognized Joe with the Guthrie Award because of his “bravery” in confronting HD, she said.
Too often conversations about HD take place “behind closed doors,” Vetter observed.
The Smith family has “made it public and they’ve created a call to action,” she explained.
HDSA CEO Louise Vetter (photo by Mike Nowak)
The community emerging as its own spokesperson
For older generations of Americans, songwriter-activist Guthrie symbolized HD.
In recent decades, with younger generations unacquainted with Guthrie, many in the Huntington’s community have attributed the lack of awareness about HD – ironically one of the most common of the rare diseases – to the lack of a celebrity such as Michael J. Fox in the sphere of Parkinson’s disease.
Without national opinion polling on HD, we can’t really know if this is the case.
What’s important is that more HD family members are telling their stories publicly than ever before, and HD is gaining exposure.
Like 33-year-old filmmaker-actress Marianna Palka, who revealed her HD genetic test results in an HBO film that premiered in June, Joe is emerging as a key new spokesperson for the HD cause.
Two other successful athletes – former Olympic rower Sarah Winckless and former National Hockey League player Jake Dowell – have shared their HD stories.
In June, another, award-winning film, the documentary The Huntington’s Disease Project: Removing the Mask, was released.
Networking for the cause
Joe’s advocacy is helped by the fact that professional baseball maintains a huge fan base.
Joe and his family have started a foundation, Help Cure HD, to raise money for research on deep brain stimulation (DBS) as a potential treatment for HD. (For years doctors have used DBS to treat Parkinson’s disease.) So far Help Cure HD has raised nearly $400,000.
Joe’s wife is Allie LaForce, a TV reporter for CBS Sports. In January, Allie did a feature on Bill Johnston, the public relations director of the National Football League’s San Diego Chargers, and his fight against HD. Bill’s wife Ramona, who has HD, now lives in a nursing home.
The main mover behind the smartly produced HDSA-San Diego galas, Bill has helped raise several million dollars for HDSA through those events and numerous others.
Bill uses his contacts in the upper echelons of business and pro sports to invite speakers like Joe and garner corporate sponsors such as the B. H. Gold Insurance Agency. HDSA also honored B.H. Gold President Bill Habeger with the Guthrie Award for his support of the cause.
“May these galas soon be victory galas,” Habeger told the audience.
HDSA-San Diego President Burt Brigida (left), B.H. Gold President Bill Habeger, HDSA CEO Vetter, and HDSA-San Diego immediate past president George Essig (photo by Mike Nowak)
From the heart, emboldening our community
As they arrived at the gala, I introduced myself to Joe, Lee, Joe’s father Mike, and Tim Mead, the Angels’ vice president for communications.
I told Joe that I was also from Ohio, that my mother had died of HD, and that I carried the genetic defect. I told him that he could rely on the San Diego chapter, HDSA, and me for anything he and his family might need in the struggle against HD.
Lee and I shared a few words about our common Cleveland connection. When she mentioned that she was 56, I said I was right there with her at 55.
At 56, my own mother had the involuntary movements typical in HD and was starting to lose her ability to reason.
Joe (left), Lee, and Mike Smith with Tim Mead, vice president for communications, Los Angeles Angels (photo by Gene Veritas)
I thought of how lucky I was to remain asymptomatic and participate fully in the gala.
After his speech, Joe asked my opinion.
“You hit it right on the mark,” I said. “You spoke from the heart.”
Later, just before the end of the gala, I spoke again with Joe. “We are brothers in this cause,” I said, putting my arm around his shoulder.
Joe raised awareness and money, but most importantly he has emboldened our fellow HD brothers and sisters to join the fight. Having every dime in the world won't bring treatments unless we have enough participants in the all-crucial research studies and clinical trials.
Joe Smith (left) and Gene Veritas (photo by Mike Nowak). Watch more videos of the gala by clicking here.
Wednesday, September 30, 2015
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.
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.
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.”
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.
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.
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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)