Monday, January 13, 2020

Planning a ‘Dancing at the Vatican’ screening to celebrate the global Huntington’s disease community’s journey


On February 19, the University of San Diego (USD) will host the world’s third screening of Dancing at the Vatican, the short documentary featuring South American Huntington’s disease-afflicted families’ historic 2017 encounter with Pope Francis at the Vatican.

As I noted in my preview before the July 2019 premiere of this 38-minute film in Los Angeles, Dancing at the Vatican captures key moments of those impoverished, disease-stricken families’ journey to their meeting with the Spanish-speaking Francis, the first Latin American pontiff in the Catholic Church’s 2000-year history. It was extraordinary: some had never ventured beyond their home towns; some even lacked birth certificates.

Now, as both an HD advocate and faculty member in USD’s Department of History, I’m helping organize the upcoming screening, and hope many more people will see it. 

Dancing at the Vatican also will be shown in London on February 5. Showings are also confirmed for Washington, D.C., in March (date and place TBA), and at the Huntington’s Disease Youth Organization conference in Glasgow, Scotland, in May. Screenings are under consideration for South America, too. Ultimately, the film will become available online.

In the words of producer and narrator Charles Sabine – like me, a presymptomatic HD gene carrier – coming together to view Dancing at the Vatican is an occasion of “extraordinary celebration” for the Huntington’s community.

An Emmy-award-winning former NBC-TV foreign correspondent, Sabine helped spearhead “HDdennomore: Pope Francis’ Special Audience with the Huntington’s Disease Community in Solidarity with South America.” Both Sabine's father and brother died from HD.

While Dancing at the Vatican captures what I called in my preview “the underside of the HD world” – families dealing simultaneously with one of humanity’s most devastating diseases and severe poverty and discrimination – it also portrays what Sabine described as “happy tales set against the dark canvas of our disease.”

At HDdennomore, and as the film recalls, Francis became the first world leader to recognize this horrible disease. And he declared that it should be “hidden no more.” 


Pope Francis with HD families in Rome, May 18, 2017 (photo by #HDdennomore)

Faith, reason, and advocacy

At USD, the primary sponsor of the screening is Frances G. Harpst Center for Catholic Thought and Culture (CCTC). Along with other USD units, the CCTC co-sponsored my trip to Rome for #HDdennomore, and also my public presentation on the event (click here to watch).

USD is a Catholic university where “faith and reason are compatible in education,” and it “welcomes students, faculty and staff of every faith tradition,” according to its statement on Catholic identity. Indeed, since my arrival in 1993, I’ve faced no restrictions on my research on abortion in Brazil, and have taught students from many religious backgrounds.

I have explored the nexus between faith and reason/science in this blog, including the in-depth article “God, Huntington’s disease and the meaning of life.”

After CCTC Director Jeffrey Burns, Ph.D., read my preview of Dancing at the Vatican last July, he e-mailed me to ask whether we could bring the film to USD. Sabine readily agreed to the idea; he’ll introduce the film and take questions afterwards.

Ignacio Muñoz-Sanjuán, Ph.D., a leading neuroscientist seeking HD treatments at the Los Angeles office of the nonprofit CHDI Foundation, Inc., also will speak. Dr. Muñoz helped organize #HDdennomore. He co-founded Factor-H, which aids Latin America’s poor HD-affected families. Both Sabine and Muñoz will also meet with students and faculty interested in their respective professional fields.

We selected the February 19 date because Sabine, based in London, will join Muñoz and several hundred researchers from around the globe the next week at the CHDI-sponsored 15th Annual HD Therapeutics Conference in nearby Palm Springs, CA. I will also attend.

In planning the screening, I’ve strengthened the bond between advocacy and academic work that USD values and that I began to establish after exiting the terrible and lonely “HD closet” in 2012 (click here to read more).


Dr. Ignacio Muñoz-Sanjuán entering the Vatican with Dilia Oviedo Guillén, a Colombian woman who lost her husband and five children to HD (photo by #HDdennomore)

A free event, with many sponsors

The screening will take place from 6:30-8:30 p.m. in USD’s Manchester Auditorium (located in Manchester Hall) and will be followed by a reception. The event is free and open to the USD community, the local HD and biomedical communities, and the public. Attendees must register at cctc@sandiego.edu or 619-260-7936.

To fund the event, we have secured support from Ionis Pharmaceuticals, Inc., the developer of the gene-silencing drug currently under study in a historic Phase 3 clinical trial by Roche. (Click here for a recent update on the trial.) Ionis is located in Carlsbad, CA, part of the San Diego-area biotech hub, one of the world’s most important. Ionis’ chief scientific officer and HD team leader, Frank Bennett, Ph.D., donated to #HDdennomore.

In addition, Roche’s U.S. subsidiary Genentech will also sponsor the screening. Headquartered in South San Francisco, CA, Genentech also has a facility in Oceanside, just north of San Diego. 

Another local company, Origami Therapeutics, Inc., is supporting the event. It also seeks to develop an HD treatment. It was founded by Beth Hoffman, Ph.D., the former president of the San Diego chapter of the Huntington’s Disease Society of America.

Other USD co-sponsors include the International Center, the Enhanced Student Faculty Interaction Fund, the Humanities Center, the above-mentioned Department of History, the Program in Latin American Studies, and the Department of Communication Studies. The College of Arts and Sciences also has lent its support.


Charles Sabine dancing at the Vatican with #HDdennomore participants (photo by #HDdennomore)

‘All of us standing together’

On January 10, I had a long lunch with George Essig, a well-connected veteran radio ad salesman and former HDSA-San Diego president. Essig’s extended family is affected by HD. As I wrote in a 2014 article, Essig “epitomizes the dedication of the unaffected relative.” (Click here to read more.)

In discussing the screening, we noted that it will be a unique event for the San Diego HD community and its supporters. Over the years, most events – such as galas, marathons, and walks – have focused on raising funds and awareness.

Echoing Sabine, I stressed that this event would be a celebration.

We brainstormed on the meaning of “celebration” for the local HD community – and for the many donors Essig has brought into the cause.

Their support had helped HD “become hidden no more,” he said. 

The screening also will be about “the evolution of the cause,” he added. 

With that in mind, Essig said he would tell supporters that he would be “remiss not to invite you to this celebration.”

The Dancing at the Vatican screening will also celebrate the progress in research, which has advanced thanks to the donors and broad collaboration in the HD community, he noted.

Essig summed it up: the Dancing at the Vatican event will be “all of us standing together and saying: I helped bring a cure to an incurable disease, even if it’s just $10 that I gave.”

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

Tuesday, November 26, 2019

An ‘electric,’ inspiring Thanksgiving for the Huntington’s disease community


Thanksgiving is my favorite holiday. I’ve reflected on it many times in this blog. For me, rather than the commercialism and stress associated with the holidays, it’s truly a day of relaxation, the warmth of friends and family, and gratitude.

This year, the Huntington’s disease community has bountiful reasons for thanks. Several clinical trials to test what might become the first effective treatments are in progress, and the community has demonstrated spirited participation.

The historic Roche gene-silencing program successfully started its crucial third and final phase, GENERATION HD1, earlier this year. The program includes an open-label extension of all 46 participants in the first phase, completed in December 2017, all of them receiving the drug RG6042 via a monthly injection into the cerebrospinal fluid (CSF).

“Two years ago, we showed for the first time – about 25 years after the discovery of the gene –the ability to lower CSF levels of mutant huntingtin [protein] in patients with HD, which was a very exciting first-in-human accomplishment, and that was really the springboard that allowed us to proceed to our global development program,” Scott Schobel, M.D., M.S., Roche’s associate group medical director and clinical science leader for RG6042, reported at the 26th annual Huntington Study Group (HSG) meeting on November 8. “So these heroic 46 volunteers were the foundation of that.”

GENERATION HD1 is “recruiting incredibly well,” Dr. Schobel said. “It’s been absolutely electric.” Total worldwide enrollment in GENERATION HD1 and related studies has surpassed 800. “It’s been a huge response from the community,” he added.

Several other programs provided updates at the HSG meeting.

Although much work remains to develop effective therapies, HD families and their supporters can feel proud for helping further the progress achieved in 2019.

Priscilla’s inspiring fight and peaceful paintings

An HD-stricken woman I know from Brazil, Priscilla Ferraz Fontes Santos, embodies the life-force of the HD cause. I saw Priscilla in 2013 at the sixth World Congress on Huntington’s Disease in Rio de Janeiro, and got to know her at #HDdennomore, Pope Francis’ special audience with the HD community in Rome in 2017.

Brazilians don’t celebrate Thanksgiving, but Priscilla’s words, paintings, and photos help us feel the peace and hope of our quintessentially American holiday.

Priscilla was stricken with juvenile HD as a teenager. She had played soccer, pursued acting, and completed her journalism degree, but the disease prevented her from finishing a second degree in tourism.

Many juvenile patients do not live past 30. Priscilla is 36. She takes no drugs to control her involuntary movements and other symptoms but instead relies on alternative and spiritual approaches, including yoga. However, she also follows HD clinical trials and hopes for a cure.

Starting November 22 and ending December 10, Priscilla and her art teacher are staging an exhibit of Priscilla’s paintings in Serra Grande, a town in the state of Bahia. They have called it “Colored Atmosphere.”



Priscilla with two of her paintings (family photo)

“The past two and a half years, I have been taking painting and art classes, and I have discovered for myself the pleasure and well-being that painting brings,” Priscilla wrote in an introduction to the exhibit. “As I await the cure, I have gained the courage to overcome many difficulties and meet challenges with the ever-present support of my family, friends, and health professionals who care for me.”

Priscilla ended with this wish: “I hope that you enjoy my paintings and that they awaken in you all of the strength, beauty, and joy with which I painted them.” (I translated the text from the original Portuguese.)

Priscilla is an “inspiration of strength and positive thinking” for all of us, Priscilla’s mother Lígia wrote in a message in Brazilian WhatsApp group dedicated to the HD cause.


Priscilla practicing yoga (family photo)

Symptom-free, but awaiting treatments

As always, I am profoundly grateful for not having yet developed any of the inevitable classic symptoms of HD, which struck my mother in her late 40s and ended her life at 68.

I turn 60 next month – an age at which my mother had full-blown HD and could no longer care for herself.

Last week, I presented my new book on Brazilian history to an audience at the University of San Diego. I had never imagined I would still be able to write at age 60.

Even more importantly, I’m able to continue supporting and loving my wife Regina and daughter Bianca. A sophomore at the University of Pennsylvania and HD-free, Bianca will spend Thanksgiving with friends in Connecticut. However, in a few weeks she will be home for winter break.

I am crossing my fingers that GENERATION HD1 and other trials can produce an effective treatment  and that I can hold on long enough to benefit and share more precious time with my family.

Sunday, November 17, 2019

‘Navigating’ the Huntington’s disease community towards crucial clinical trials


As scientists and drug companies expand the array of potential treatments for Huntington’s disease, the Huntington Study Group (HSG), the world’s largest HD clinical research network, is redoubling its efforts to educate the HD community for current and upcoming clinical trials and train the necessary medical personnel.

A record 700-plus participants focused on these themes at the 26th annual HSG Meeting, titled “HSG 2019: Navigating HD,” November 7-9 at the Hyatt Regency hotel in Sacramento, CA. (Attendance at the HSG 2017 and 2018 meetings was over 600.)

Clinical trials are crucial for demonstrating drug safety and efficacy. The number of HD trials has increased in recent years, bringing hope for better treatment of the devastating symptoms and perhaps even an attack on the root causes. Key trials in progress include GENERATION HD1, run by Roche, and SIGNALadministered by the HSG and Vaccinex.

“Figuring out how these trials are going to work, what they’re aiming to do, and what an individual patient or family should do to get involved or not get involved has become complicated, to some extent,” Andrew Feigin, M.D., the HSG chair and a professor of neurology at New York University Langone Health, told me in a November 6 interview. “That’s my interpretation of the ‘navigating HD.’ We’re trying to get at some of these novel therapies and clarify where they’re headed, where they stand, how the HSG can get more involved, and figuring out where people can go for the cutting-edge therapies for Huntington’s disease.”

In the conference-opening “HSG State of the Union” presentation by HSG leaders and staff, executive director Shari Kinel, J.D., reported that the event involved 15 countries, 23 companies, 9 advocacy groups, 17 sponsors, and 15 exhibitors. The sponsors included Roche’s American subsidiary Genentech and Vaccinex.

“This incredible showing […] is a sign that the HSG has more partners, more colleagues, more friends than ever who are engaged, dedicated, and committed to seeking treatments that make a difference for those impacted by Huntington’s disease,” Kinel told the audience.

Dr. Feigin affirmed that in the past year, the HSG has doubled its paid staff from four to eight, plus one part-timer, although he declined to reveal the organization’s annual budget. Headquartered in Rochester, NY, the HSG is mainly funded by firms like Vaccinex that it partners with on clinical trials, he explained. Sponsors cover the cost of the annual meeting.


The audience watches a presentation by Dr. Arthur Combs at the "HD Innovators Forum" at the 26th annual HSG Meeting (photo by Gene Veritas, aka Kenneth P. Serbin)

A full-service organization

The HSG was founded in 1993, the year of the discovery of the huntingtin gene. Dr. Feigin described the nonprofit organization as a “full-service” contract research organization that can carry out all aspects of an HD clinical trial.

In her speech, Kinel stated that the HSG member network includes 801 investigators (researchers), trial coordinators, scientists, and HD experts. Around the globe, the organization has credentialed 127 sites for HD trials, and HSG members have worked with more than 21,000 HD-affected individuals, she said.

The HSG also developed the Unified Huntington’s Disease Rating Scale (UHDRS), the primary assessment tool in HD clinical trials. It consists of tests of a person’s movements, cognition, behavior, independence, and functional capacity.

The “HSG State of the Union” presentation outlined the HSG’s mission, accomplishments, clinical trials, educational activities, efforts to improve patient care, and plans for the future.

You can watch the presentation in the video below. Click here for my video album of the event, which included a variety of presentations on patient care, clinical trial techniques and measurements, new scientific findings, and innovations in drug and clinical trial development.


Seeking a better drug to treat chorea

Prior to the main conference, the HSG held organizational meetings for KINECT-HD, a Phase 3 clinical trial by the HSG and San Diego-based drug developer Neurocrine Biosciences to test the efficacy of valbenazine to treat chorea, the involuntary movements typical in HD. 

The HSG ran the successful clinical trials of two other drugs for chorea, Xenazine and Austedo, the only HD-specific medicines to receive approval from the U.S. Food and Drug Administration (FDA). On November 14, it issued a press release announcing the start of the 18-week trial, which seeks to enroll HD-affected individuals with chorea at 55 sites in the U.S. and Canada.

In 2017, valbenazine was approved by the FDA with the name Ingrezza for the treatment of tardive dyskinesia, an irreversible involuntary movement disorder. This status allowed Neurocrine and the HSG to take it directly into a Phase 3 trial for HD.

Like Xenazine and Austedo, valbenazine is a VMAT2 inhibitor. Xenazine requires three daily doses, and Austedo two

“The upside thing of valbenazine is that it’s a drug that can be dosed once daily,” said Dietrich Haubenberger, M.D., the Neurocrine medical director, in a presentation forming part of the “HD Research Round-Up” at the close of the scientific sessions on November 8.

Wearable sensors and the search for biomarkers

In the quest for HD treatments, researchers hunt for new biomarkers, that is, signs of the disease and the effect of remedies. Biomarkers are especially critical in brain-related diseases, because doctors cannot do biopsies on the organ.

With a key innovation, KINECT-HD will also look for biomarkers. It will be the HSG’s first trial in which participants use wearable sensors – for continuous monitoring of their movements and other biological functions, even at home. Researchers hope this more detailed monitoring will provide both a better understanding of chorea and valbenazine’s impact on it.

Called BioStamp nPoint, the sensors were designed by MC10, Inc., and cleared for use by the FDA. MC10 is based in Lexington, MA.

MC10 chief medical officer Arthur Combs, M.D., described the system at the conference’s “HD Innovators Forum.”

“It weighs less than eight grams [0.28 oz.],” Dr. Combs said, explaining that the sensor can be placed anywhere on the body and worn even during showers and swimming. “It’s like putting on a Band-Aid.”

MC10 developed 44 algorithms for the system to help measure trial participants’ data. In addition to chorea, BioStamp nPoint will help investigators observe individuals’ gait, heart rate, sleep, posture, and other bodily functions, Dr. Combs added.

In one previous study, “patients with symptomatic Huntington’s disease spent 50 percent of their day” lying down, he explained. That may be a response to exhaustion or the risk of falling, he said. Thus, the BioStamp nPoint system could help determine whether lying down is a “marker” for the disease, and whether less time at rest is a sign of drug efficacy, he said. It also accounts for the uniqueness of each patients, he added.

To obtain continuous data in GENERATION HD1, Roche developed an HD Digital Monitoring Platform, with participants wearing a smartwatch and using a smartphone.

You can watch Dr. Combs’ presentation in the video below.


The latest clinical trial news

In addition to Neurocrine, other firms reported on their clinical trials during the “HD Research Round-Up”: Voyager Therapeutics, uniQure, Wave Life Sciences, Vaccinex, and Roche.

The Roche GENERATION HD1 update of the company’s historic Phase 3 clinical trial of the drug RG6042 was one of the most anticipated. A gene-silencing drug, RG6042 is aimed at the roots of HD and caused a stunning improvement in the health of HD-affected mice. On October 14, Roche announced that it was expanding the number of trial participants from 660 to 801 and adding China to the nearly 20 countries in the study.

The announcement noted that recruitment in the U.S. had “exceeded expectations” and was now complete. Expanding the number of volunteers and adding China will allow for more abundant data and the study of a more diverse population, Roche said.

Enrollment for the Roche HD program has been “absolutely electric,” with over 800 individuals already in 2019 in GENERATION HD1 and related HD studies, said Scott Schobel, M.D., M.S., Roche’s associate group medical director and clinical science leader for RG6042 (click here to watch Dr. Schobel’s presentation). If the trial is successful, Roche will apply for drug approval from the FDA and regulatory agencies in other countries.

On November 9, HSG held a “Family Day” for the HD community, with presentations by advocates like me, presentations by scientists, and an update on GENERATION HD1.

In upcoming articles, I will report on Family Day and more of the scientific and clinical developments discussed at the meeting.

Disclosure: my travel expenses were covered by the HSG and the Department of History of the University of San Diego.

Friday, October 18, 2019

Are we failing to stop Huntington’s disease by ignoring ‘natural’ remedies, alternative therapies, and repurposed drugs?


This article is Part 2 of a two-part series.

Because Huntington’s disease is so devastating and intractable, many affected individuals and presymptomatic gene carriers like me have chosen to take substances outside the pharmaceutical mainstream to try to forestall the inevitable onset or worsening of symptoms.

The reason: 26 years after the discovery of the huntingtin gene, despite significant progress in understanding the disease, there is no effective therapy or cure. 

In Part 1 of this series, Robert Pacifici, Ph.D., the chief scientific officer for CHDI Foundation, Inc., discussed the immense progress made in HD research and the optimistic prospects for developing therapies. CHDI is the largest nonprofit effort aimed at defeating HD.

Only two drugs addressing symptoms of HD have been approved by the U.S. Food and Drug Administration (FDA) – Xenazine in 2008 and the similar, improved drug Austedo in 2017. Both treat the involuntary movements in HD (chorea) but do not attack the causes or halt progression of this fatal disorder. (Click here to read more.) 

Physicians also prescribe medications – nonspecific for HD – to alleviate the difficult behavioral and psychiatric symptoms. Those drugs also have no effect on progression.

Trying supplements

My mother died of HD in 2006 at age 68. As I desperately witnessed the disease’s inexorable onslaught on her mind and body, I embarked on a controversial “treatment now” program of unproven but certainly not quackish supplements, the Huntington’s Disease Drug Works (HDDW) regimen developed by veteran HD physician LaVonne Goodman, M.D. 

Starting in 2005, I introduced the supplements into my diet in steps. I worked up to a daily routine in which I took 75 grams of trehalose, a sugar that seems to help the brain clear cellular debris; 600 mg of medical-grade coenzyme Q-10 (which I had taken on and off since 1996); two g of omega-3 oil; two g of blueberry extract; and ten g of medical-grade creatine. (Click here to read more.)

For several years I participated as a subject in an HDDW online observational study, performing cognitive tests on a home computer. In this very small study, several early or midstage HD-affected people showed stabilization or improvement. Late-stage patients did less well, continuing to progress with the disease. The study was too small for its results to be applicable to the general HD population. (Click here to read more.)

I was the only presymptomatic gene carrier in the trial. Afterwards, I continued the regimen on my own, but regularly consulted with Dr. Goodman.

In 2014, I stopped coenzyme Q-10 and creatine after clinical trials proved them ineffective. Recently, in place of expensive high-grade omega-3 pills, I’m eating more fish. Annually, I’ve spent thousands of dollars on supplements – none covered by health insurance.

I have also sought to lead a healthy lifestyle, including intellectual and social enrichment. Doctors and researchers encourage this and have pointed out that it could be part of why I have long passed my mother’s age of onset, although there is no scientific proof  (Click here to read more).

The HDDW program and the clinical trials for coenzyme Q-10 and creatine were the most formal testing of supplements. HD-affected individuals have tried and/or discussed a range of other substances, including injections of live fetal shark cells, the amino acid cysteine, medical marijuana, and the highly popular – but potentially harmful – marijuana and hemp extract cannabidiol (CBD), usually by drinking an oil.



Above, CBD products in a Los Angeles, CA, grocery store (photo by Deceptitom [CC BY-SA 4.0 {https://creativecommons..org/licenses/by-sa/4.0}]). Below, the supplements I have taken (photo by Gene Veritas, aka Kenneth P. Serbin)



One group of advocates has also pushed for a clinical trial of methylene blue, a dye under study as a possible way to alleviate a variety of medical conditions.

In our recent interview, Dr. Pacifici and I delved into whether CHDI and the HD community are failing to defeat the disease by ignoring these types of alternative approaches, including so-called “natural” remedies and repurposed drugs. The video of our interview is posted at the end of this article.

HD-specific drugs needed

Citing the increased interest in HD in the pharmaceutical industry (discussed in Part 1), Dr. Pacifici said that CHDI would assist any company aiming to test an HD drug, as long as it’s safe, tolerable, and backed with enough resources to do a careful clinical trial.

“It’s wonderful that there’s this diversity of folks that have assets and try and come into the field, as long as they’re credible and well-thought-out,” he said.

However, because of HD’s genetic cause and complexity, CHDI has stressed that drugs for halting disease progression must be “new chemical entities” and HD-specific.

Dr. Pacifici pointed to an example: difficulties with sleep, a serious symptom of HD. The HD field must consider: “What are the things that are probably going to happen out there anyway, because there’s a big market for sleep medications versus the things that are very specific to HD, that if we don’t do them, they’re not going to get done?”

Don’t expect to win the jackpot

The need for unique HD drugs, and the overall history of drug discovery, point to the fact that so-called “natural” approaches and repurposing of other drugs will not result in effective treatments, Dr. Pacifici asserted.

The alleviation of Dr. Pacifici’s own suffering from familial Mediterranean fever (FMF, discussed in Part 1) resulted from the discovery of the drug colchicine, “a natural thing from the crocus flower” already in use to treat gout. Such a scenario is atypical, he explained.

“Obviously, I didn’t just win the Lotto,” Dr. Pacifici said. “I won the Mega Millions with the fact that I happen to be treated by an existing drug. It’s pretty rare.”

The HD community should not expect such an outcome, he said.

“Obviously the thing that’s wonderful when that does happen is that there’s no path that’s shorter from a discovery to a treatment,” he continued. “But the effect has to be pretty overwhelming.”

Indeed, colchicine “completely stopped” the recurrent abdominal pain and fever of FMF. 

“You can imagine,” he said, “that observation’s a little harder to make in Huntington’s disease, given the slow progression of the disease, given the myriad of symptoms.”


Robert Pacifici, Ph.D. (photo by Gene Veritas)

Is ‘natural’ better?

The notion of “natural” products is a bit “artificial,” Dr. Pacifici pointed out.

“People, first of all, seem to think that something that’s ‘natural’ is better,” he said. “There are plenty of horrible poisons like ricin that are natural, and if you take them, they kill you. It’s ‘organic,’ and it’s ‘natural.’ That doesn’t mean it’s good for you!”

We discussed a clinical trial for an eye disease using liquid from the resin of the mastic tree from the Greek island of Chios, as reported by New York Times columnist Frank Bruni. For thousands of years, people have used the resin to address many types of health problems. The trial seeks to test whether the liquid can repair damaged nerves in the eye, with potentially positive implications for people with Alzheimer’s disease and other neurological conditions.

Dr. Pacifici said that, in such a study, scientists need to know the exact chemical makeup of the substance and, in the case of a possible HD treatment, determine whether that makeup is any different from other compounds CHDI has tested.

In the case of the mastic tree, scientists also need to ensure that weather conditions and the conditions of the tree do not alter the makeup of the resin. Also, the testing of the substance needs to be “reproducible,” he explained. 

That the compound in the liquid comes from a natural source is irrelevant, he added, because scientists can produce such compounds in a lab.

Clinical trials are expensive, costing hundreds of millions of dollars, Dr. Pacific observed. Ultimately, CHDI and HD researchers need to avoid “taking empty shots on goal that we could have predicted up front had no chance of working.”

Millions of experiments

Not long after its founding in 2003, CHDI did a project to ensure that the HD field did not miss a possible remedy among existing drugs and other substances, some of them natural. According to Dr. Pacifici, the foundation worked with a small firm that had a library of all FDA-approved drugs and also substances such as vitamins and other generally safe items, including some shown to be safe and tolerable in Phase 1 clinical trials.

“We tested all of those,” Dr. Pacifici recalled, referring to the entire library. “In fact, we tested all of those at multiple concentrations. In fact, we tested all of those at multiple concentrations with each other, in pairwise fashion [two drugs at a time].”

Carried out in cells, the tests ran into the millions, he said.

“But we found nothing that suggested, ‘Yeah, there’s the Mega Millions hit or combination of things that should go forward,'” he said.

The massive experiment confirmed the need for a unique, HD-specific type of medicine that could be delivered to the brain safely over a long period of time, thus attacking the specific problems caused by the disease, Dr. Pacifici observed.

Through Enroll-HD, the CHDI-sponsored global study of HD-affected individuals and their families, CHDI tracks unusual data from visits to HD clinics that might suggest follow-up to discover further clues for developing drugs.

The CBD ‘craze’

As a September 29 CNN documentary reported, in the United States production and use of CBD for health reasons has boomed in the last six years. The unregulated proliferation of CBD-containing products such as tinctures, foods, and oils has left the public with little reliable information on the risks, including items with harmful impurities.

“The CBD craze that we’re in, I think, is unprecedented really in the history of medicine,” Donald Abrams, M.D., a leading cannabis researcher, said in the broadcast. “It’s a compound that has gotten way ahead of any research to support the claims that are being made.”

Dr. Pacifici, who’s studied the issue closely, echoed these concerns. Tetrahydrocannabinol (THC), CBD, and other marijuana-based compounds are “enjoying their moment in the sun” because of legalization for recreational and medical use in some states, although not federally, he observed. “It’s kind of the flavor of the month, if you will.”

Only one approved CBD drug

CBD is a “real compound,” he explained.

However, there is only one FDA-approved drug made from CBD, Epidiolex, manufactured by the British firm GW Pharmaceuticals. Epidiolex was shown to be safe and efficacious in the treatment of two types of childhood epilepsy.

GW Pharmaceuticals had to run “through the same paces as any other drug substance,” Dr. Pacifici remarked. “They happened to get it out of the marijuana plant. That’s fine. I don’t care where it comes from. But it’s highly purified and highly quantified so that they know exactly what’s in there and what’s not in there and the purity of it.”

No other CBD product has been tested in a clinical trial.

In Dr. Pacifici’s view, because of the lack of quality control and regulatory approval in the making of CBD products, a critical question remains: “Are people who are experimenting with it actually getting real, pure CBD?” In some cases, the products do not even contain CBD, or have an incorrect concentration.




CBD not yet tested for HD

Could CBD potentially treat Huntington’s disease?

 “The short answer is, we don’t know,” he asserted. “I can’t tell you of the number of fantastic ideas that I’ve had. Wonderful ideas, that I sit down, I think, ‘I’ve had this eureka moment.’ Until you test it, and you find out that biology is more complicated than you thought.”

Scientists, he said, know about CBD’s “pharmacology” – its function, effects, and where it gets into the body. “Is it something that could potentially have a beneficial effect? Sure. But has it been properly tested, especially in HD? Absolutely not.”

Many researchers are currently focusing on CBD for HD, and they have developed some very reasonable hypotheses, he said.

“To my mind, none of them, yet, have reached a level of evidence where somebody wants to go spend a hundred million dollars or more on a trial to see if it’s actually efficacious,” he said. “Maybe they will.”

Insufficient evidence on methylene blue

Regarding methylene blue, Dr. Pacifici observed that research is currently insufficient, “so I don’t think any of us can say definitively that it will work or it won’t work.”

“Isolated examples” show that it might be efficacious, but that’s not enough “evidence to actually run a full-blown human clinical trial,” he explained.

Produced by HD community members in 2016, The Blue Solution video suggests that families can consult their doctors about methylene blue.

However, Dr. Pacifici cautioned against this approach.

“A lot of times people have said things like, ‘Well, as long as it doesn’t do anything bad, why not take it,’” he remarked. “I think that’s a little bit dangerous. First of all, you never really know whether or not something is safe and well-tolerated until it’s tested.

“There are examples of opportunity costs. There are people who were on Co-Q 10 who were not allowed to participate in other, real trials because they were loaded up with Co-Q 10. So, the idea that ‘it’s probably safe, and I’ll take it in case it is good,’ I wouldn’t certainly advise somebody to go just based on that limited amount of evidence.”

Diet and lifestyle

I asked Dr. Pacifici why so little research has focused on HD and diet and whether it should.

“It doesn’t surprise me that people are curious about this,” he said, citing the example of Lorenzo’s Oil, a nutrition-based treatment developed for adrenoleukodystrophy, a deadly genetic brain disorder rarer than HD.

“In fact, we’re very careful,” he said of CHDI’s mission. “One of the reasons we say that we’re trying to accelerate ‘therapies’ for HD – we don’t say accelerate ‘drugs’ – is because we don’t know what shape that therapy could take. We want to be deliberately inclusive. In fact, I wouldn’t even limit it to diet. I would say ‘lifestyle.’”

He recalled the research of Jenny Morton, Ph.D., who works with transgenic HD mice and sheep. Dr. Morton observed in an experiment that HD mice had erratic sleep schedules – as do HD-affected people. She placed them with normal mice, giving them sleeping and wakeup pills, and gave them things only at night, a mouse’s normal time for activity.

“She was able to show that those mice now absolutely were back to their regular rhythm – they had no choice – and actually it was very beneficial for them,” Dr. Pacifici noted. “They actually even lived longer.”

Keeping our eye on the ball

With the advent of historic clinical trials such as the Roche Phase 3 gene-silencing program, “we’re at a stage now where there are some unbelievably compelling drug candidates,” Dr. Pacifici remarked.

“I guess the question we have to ask ourselves is: how much do we want to take our eye off the ball?” he asked. “Imagine how tragic it would be if there was something that collectively we, with CHDI’s involvement, could do to make those things successful and we were distracted with something else that had much lower probability of success.”

The HD community needs to “discipline” itself to focus on the “very best” possibilities for treatments and avoid “diluting our efforts the way we did in the old days” and “detracting resources.”

For a disease as complex and devasting as Huntington’s, there are no easy answers. The HD community – affected families, scientists, advocacy organizations, foundations, and our supporters – must continue the hard but brave march towards therapies.

CHDI: many 'irons in the fire' in quest for Huntington's disease therapies from Gene Veritas on Vimeo.