As range of possible therapies grows, CHDI expands efforts to defeat Huntington’s disease

This article is Part 1 of a two-part series.

CHDI Foundation, Inc., the largest nonprofit effort aimed at developing therapies for Huntington’s disease, has expanded its efforts and partnerships to accelerate the defeat of the deadly disorder.

That’s the message transmitted in a July 29 interview by Robert Pacifici, Ph.D., CHDI’s chief scientific officer, who has a very personal commitment to disease eradication, and in a July 13 public presentation by Douglas Macdonald, Ph.D., CHDI’s director for research operations and scientific alliances.

CHDI emerged in 2003 out of the Hereditary Disease Foundation, where it was known as “The Cure Huntington’s Disease Initiative.” Funded by donors who wish to remain anonymous, “CHDI” is no longer an acronym but simply part of the foundation’s name.

According to Dr. Pacifici, and as reported previously in this blog, CHDI continues to spend $100 million annually on HD research and programs. The number of staffers at its offices in Los Angeles, CA, New York, NY, and Princeton, NJ, has grown to 100, doubling in ten years.

A virtual biotech firm, CHDI has no labs. Instead, it partners with, funds, and outsources projects to contract research organizations (CROs), academic labs, and pharmaceutical and drug discovery companies like Ionis Pharmaceuticals, Inc., the developer of RG-6042, a gene-silencing drug now in a historic Phase 3 clinical trial run by Roche. Roche took over the license after an Ionis Phase 1/2a trial successfully and safely lowered the amount of huntingtin protein, normal and mutant, in trial volunteers’ cerebrospinal fluid (CSF). Roche is now evaluating whether this reduction of huntingtin protein leads to clinical benefit (efficacy) in the Phase 3 trial.

“On any given day, there are about 700 other people who are supported by CHDI that are working on various aspects of the drug discovery and development pipeline that we try and orchestrate and integrate and enable,” Dr. Pacifici told me at the Los Angeles office, which is strategically located three miles from the city’s international airport.

CHDI seeks to “push the field forward” towards effective treatments and other “therapies,” which could include approaches other than drugs, he explained.

However, unlike private for-profit firms, CHDI does not seek to grow or perpetuate itself: “We actually don’t want to build a big company. We’d like to dissolve CHDI, because our job is done.” 

CHDI is motivated by “time, not money,” because it wants to “accelerate” the discovery of therapeutics, Dr. Macdonald said in his talk at the Fourth Annual Convention of the San Diego Chapter of the Huntington’s Disease Society of America (HDSA-San Diego).

“We don’t have any competitors,” he added. “We only have collaborators.”

Robert Pacifici, Ph.D. (photo by Gene Veritas, aka Kenneth P. Serbin)

An in-depth look

You can watch my interview with Dr. Pacifici, my recording of Dr. Macdonald’s presentation, and the 2019 CHDI research highlights report, Postcard from Palm Springs, in the videos at the end of this article.

I first met Dr. Pacifici in December 2007, when he spoke at a “Spotlight on Huntington’s Disease” that I organized at the University of California, Los Angeles, for the oversight board of the California Institute for Regenerative Medicine, the state’s $3 billion voter-approved stem cell initiative.

In 2009, I visited a CHDI office for the first time, in Los Angeles, to interview Dr. Pacifici and other scientists to learn more about the organization. Since then, I have done seven video interviews with Dr. Pacifici – during the foundation’s annual HD Therapeutics Conference in Palm Springs, CA – to obtain snapshots of the progress towards treatments. In 2011, I keynoted the sixth conference in a major step out of the terrible and lonely HD closet. 

Our July 29 interview was our ninth overall and, at 82 minutes, our longest and most in-depth. I sought to gain perspective on CHDI and the overall efforts towards therapies. I also wanted Dr. Pacifici’s assessment of so-called natural and alternative remedies used by some in the HD community, such as CBD oil, and also of the potential role of repurposed drugs – the topic of Part 2 of this series.

I first came in touch with Dr. Macdonald because he was CHDI’s point person for collaborations with Ionis and other gene-silencing projects. His July talk in San Diego was the most comprehensive public presentation of CHDI’s activities in lay terms that I have seen. (Also see Dr. Pacifici’s June 28 overview of CHDI at the 34th Annual HDSA Convention in Boston.)

Recording these two scientists in July and exploring their ideas once again helped me cope with my status as an HD gene-carrier and, I hope, contributed mental stimulation to help delay the inevitable disease onset. (Click here to read more.)

July 2019 marked a personal milestone for me: not only tracking CHDI for a decade, but also living symptom-free.

Douglas Macdonald, Ph.D., at the 2019 HDSA-San Diego chapter convention (photo by Randy Oto)

Battling genetic diseases

In interviewing HD scientists, I often ask what led them to focus on HD, a rare disease, rather than more common afflictions. In Dr. Pacifici’s case, his own family’s struggle against familial Mediterranean fever (FMF) motivated him to become a drug hunter and ultimately focus on HD.

“Like, unfortunately, too many of you, my family also had a rare genetic disorder,” he said, referring to the HD community and FMF.

Dr. Pacifici explained that FMF caused his father to have “recurrent bouts of horrible stomach pain and elevated fever and eventually ended up passing away from complications related to the disease at the very early age of 47, when I was just four years old.”

As a result, Dr. Pacifici had firsthand knowledge of a genetic disease’s “devastating” impact on a family.

“The thing that’s really crazy is that it turns out that the disease is now treatable, and it’s treatable with a drug that’s been around a very long time,” he said. “It’s a natural thing from the crocus flower called colchicine.”

Colchine was introduced as a treatment in 1972. However, as with HD, there is no cure. 

Dr. Pacifici pointed out that, tragically, each day his father passed by a pharmacy that carried colchicine, but before a doctor in Turkey using the drug to treat gout had noticed that gout patients with FMF also got relief from that condition.

As a child, Dr. Pacifici, who grew up in New York City, took part in FMF clinical studies at the National Institutes of Health (NIH) in Bethesda, MD. At 8, with the discovery of colchicine as an FMF treatment, he started taking the drug, as did his 24-year-old brother. Dr. Pacifici’s son also inherited the disease and takes colchicine.

The HD gene is dominant, with each child of an affected parent having a 50-50 chance of inheriting the mutation, which inevitably brings on the disease. The FMF gene is recessive, which means that an individual must inherit a copy from both parents.

“As it relates to HD, I’ve experienced the tragedy of a drug that comes too late, in the case of my dad,” Dr. Pacifici said.

He added that his story is also relevant because “we scientists very often ask for HD families to participate in clinical trials.”

“There’s nothing that’s more precious to a drug hunter than an observation in the population you seek to treat,” he said, echoing a frequent theme of his interviews and talks. “I think I can speak to the challenges and difficulties of participating from the patient perspective – and certainly in the advantages and the upside of that – because I participated in clinical trials before colchicine was discovered.”

Dr. Pacifici recalled giving “what seemed like gallons of blood every time I visited [the NIH] in the hopes that somehow the material that I was providing would enable research and help further a treatment. When I ask folks to participate in clinical trials, I know what a big ask I’m making, but I also know what the upside and the advantages are.”

In Part 2 of this series, Dr. Pacifici addresses colchicine’s attributes – its “natural” source and its repurposing as a drug for FMF – as potential drug development models for HD.

First, find out what’s broken

According to Dr. Pacifici, with CHDI’s help the field of HD drug development has matured to a point where major pharmaceutical companies like Roche conduct critical clinical trials, expecting a potential business payoff.

A decade ago, attempts to develop treatments were based on a “shallow understanding” of HD, he said. 

CHDI has encouraged labs to deepen our understanding of the disease. Scientists have needed to discover what’s “broken” in HD before they can attempt to fix it, he explained.

As a result, the 1993 discovery of the gene “has finally, finally been leveraged,” Dr. Pacifici observed. Currently, just in the category of gene silencing approaches like RG-6042, at least eight different types of treatments are in clinical development. (Companies with advanced programs include Wave Life Sciences, Takeda, uniQure, and Voyager Therapeutics.)

“They all share the common theme that they’re trying to turn off the huntingtin gene or reduce the amount of toxic huntingtin protein that’s present in cells,” he noted.

“There’s never been a more promising time in HD drug discovery and development,” Dr. Pacifici concluded, cautioning that in drug development there are no “guarantees.”

Scientists at the 2019 HD Therapeutics Conference (photo by Gene Veritas)

De-risking clinical trials

The progress in research has made for improvement in the design of clinical trials and ultimately the chances of their success, Dr. Pacific explained.

CHDI’s job as a nonprofit “is to do what’s called de-risking, to make a project look more and more attractive,” he said. “Because when it comes to later-stage clinical development, we want and need those big companies to come in.”

A major example: with Dr. Macdonald working as coordinator, CHDI and collaborating labs, CROs, and physicians developed a key technique (assay) to measure the amount of mutant huntingtin protein in clinical trial volunteers’ CSF, which runs along the spine and bathes the brain. Ionis then used this assay in its Phase 1/2a trial. In the trial, investigators draw CSF samples from volunteers via lumbar puncture. This is sometimes called a spinal tap, and is similar to an epidural procedure that many women undergo when giving birth.

To accelerate the quest for treatments, CHDI openly shares of all its HD-related data and resources. Thus, the CSF huntingtin test is available to all companies and researchers. “This exact assay is now being used in all of these [huntingtin lowering] trials,” Dr. Macdonald said in his talk.

Dr. Macdonald added that, instead of grants, CHDI uses contracts in its partnerships, with mandatory reporting of lab results. As explained by Dr. Pacifici at the HDSA convention, this business model gives CHDI “laser-like focus” on HD, preventing partners from getting sidetracked with discoveries potentially helpful in other diseases.

In addition, CHDI sponsors Enroll-HD, a global database, clinical research platform and observational study of HD-affected individuals and their relatives, now numbering more than 20,000. Enroll-HD seeks to improve clinical trials, facilitate access to them, and improve clinical care.

CHDI has established centralized biomaterial/reagent repositories of mice, cells, DNA, antibodies, and patient samples (such as blood) that researchers can access.

CHDI has also worked with the nonprofit Critical Path Institute to form the Huntington’s Disease Regulatory Science Consortium (HD-RSC) to create new tools and methods to advance efficient clinical development and address the regulatory needs for approval of HD therapeutics. Participants include Roche and other pharmaceutical and biotech firms, technology companies, academic institutions, nonprofit biomedical research institutions, and advocacy organizations.

According to Dr. Pacifici, these entities are “collaborating with each other to interface with the EMA (the European Medicines Agency) and the Food and Drug Administration (FDA) to figure out how we can design better, faster, more sensitive trials, even trials that involve people who are much earlier in the disease and not symptomatic. We’d like to have people treated as early as possible, before a lot of the damage occurs in the brain, and when the drug has the best possibility to exert its effects.”

In these types of collaborations, CHDI leverages its connections, nonprofit status, and independence to help position clinical trial programs for success, he added.

Roche’s ‘breathtaking’ investment

As a result of such de-risking, “there’s been a ton of interest” in HD among drug companies, Dr. Pacifici observed. The industry has also taken careful note of the Roche project.

“These are numbers of people and numbers of dollars and numbers of sites and a sophistication that are breathtaking, when you look at the investment that needs to be made,” he said, referring to the RG-6042 trial, which will include a total of 660 volunteers at more than 90 sites in at least 18 countries. “How wonderful that you’ve got this professional organization that’s done that part of the pipeline time and again.”

Because the field has advanced to human clinical trials (as opposed to experiments in animals), researchers will learn more than ever before about the disease and potential drugs, and they’ll be doing it faster, he said.

Roche is injecting RG-6042 into the trial volunteers through a lumbar puncture. If the drug lowers the level of huntingtin protein successfully in the right place and at the right time and produces an improvement either in the course of disease progression or certain symptoms, incentive will grow for companies to develop an oral pill. (In 2018, CHDI teamed up with PTC Therapeutics to investigate that possibility.)

The news in March that Roche would reduce the lumbar punctures from monthly to bi-monthly in the 25-month trial “is an indicator of very positive things,” and that the trial administrators are already learning from the experiment, Dr. Pacifici observed. 

With the billions of dollars spent on many unsuccessful trials for Alzheimer’s disease and other neurological disorders, companies are also turning to HD as a potential template for developing treatments for those conditions, Dr. Pacifici added.

Alternatives to huntingtin lowering

Dr. Pacifici said that he is “very happy to see the number of different, complementary programs” aiming to lower the mutant huntingtin protein.

However, he added that it “would be foolhardy to have a monolithic portfolio and say that’s the only mechanism. Because if for some reason – it’s still formally possible – that none of these therapies will actually have the beneficial effect we’re all hoping and praying for, we don’t want to start from scratch in five years and say, ‘Gosh, I wish we had some other irons in the fire.’”

Indeed, although knowledge about both the normal and mutant huntingtin proteins has increased substantially, it’s still not clear whether the mutant protein causes the disease, although experiments in mice showed that the Ionis drug relieved and even reversed symptoms.

“We still don’t [know] with unabashed certainty,” Dr. Pacifici admitted. “That may sound frustrating for people. But in science, to know – to rule something out definitively – is pretty difficult.”

However, he pointed out, different explanations are not necessarily mutually exclusive. For example, both the proteins and the RNA (which carries the message from the DNA to make the protein) could both be toxic, he said. The critical question, he noted, is how does such knowledge impact the drug-making process? Other newly discovered aspects of huntingtin biology are adding further nuance to the drug-making process, he said.

Thus, CHDI is looking at alternatives to lowering the huntingtin protein. In particular, over the past five years it has included a new focus on the genetic aspects of the disease made possible by dramatic scientific discoveries.

Modifier genes: nature delays or speeds onset

A major example involves so-called modifier genes, that is, genes other than the huntingtin gene that delay or speed HD onset. Using data from over 9,000 HD gene carriers and their family members, an international group of researchers (known as the GeM-HD Consortium) has identified 23 potential modifier genes. This type of broad-ranging study is known as GWAS, genome-wide association study. (Click here for the 2019 CHDI presentation “Genetic Modifiers” by Marcy MacDonald, Ph.D., no relation to Douglas.)

Some of the modifiers delay onset, whereas others hasten it, Dr. Pacifici explained. Next to huntingtin lowering approaches, modifier genes and related issues make up CHDI’s second major strategy for defeating HD.

Normal gene carriers normally carry ten to 25 so-called CAG repeats on their huntingtin gene – letters and words in the genetic alphabet. The disease usually occurs in people with 40 or more repeats.

Dr. Pacifici pointed to the example of people with 40 so-called CAG repeats on the huntingtin gene. The average age of onset for those with 40 repeats is about 50. However, data reveal outliers experiencing onset as early as 25 and late as 65, a 40-year difference.

“Imagine if we had a drug that could delay onset of motor symptoms by 40 years!” Dr. Pacifici exclaimed. “My gosh, that would be fantastic. Nature’s kind of done that experiment for us. It’s told us that it is possible to modulate the disease.”

The key now is for drug developers to create a drug based on what nature did, he pointed out, adding that CHDI has formed an internal group to further research modifier genes.

At the HDSA convention, Dr. Pacifici outlined some of the other crucial findings from the GWAS research. Some people’s CAG repeats are interrupted with a CAA, in effect shortening the chain of CAGs. “You actually get the disease later,” Dr. Pacifici stated.

According to Dr. Pacifici, another finding has demonstrated that somatic expansion – a further expansion of the mutation – can occur in people with the genetic defect, thus hastening symptoms. In other words, over a lifetime, the CAG repeats can actually increase, say, to 100 or more, thus causing brain cells to die. (Early in life, much higher numbers of repeats cause juvenile HD.)

(This research could possibly explain why my mother and I, both with 40 repeats, have had different experiences with HD. She probably had onset in her late 40s and died at age 68. I am 59 and, at my HD checkups earlier this year, did not shown apparent symptoms. At 59, my mother had full-blown HD. I will explore this topic in a future article.)

In his convention talk, Dr. Pacifici also reported on CHDI’s collaboration with IBM, which has produced a model of the disease with nine stages instead of the traditional four. This ongoing project will help design better clinical trials, he said.

We still need to ‘roll up our sleeves’

The complexities of HD and the fact that people will probably need different kinds of therapies depending on their age and individual characteristics underscore the likely need for a Huntington’s cocktail, that is, a combination of therapies, Dr. Pacifici observed.

I first heard the idea of a cocktail mentioned at an HDSA leadership conference in 2000, and it’s recurred frequently.

The elements of that cocktail, of course, remain to be assembled. I asked Dr. Pacifici to expand on a comment he had made in 2009: that the answer for successfully treating HD will come out of “left field.”

“Amazing events” can still occur in scientific research, he explained. However, more specifically, Dr. Pacifici referred to the fact that “99.9 percent of biomedical research” happens outside of the sphere of HD and CHDI, with reams of publications in academic journals and in patent applications.

“It’s not so much that we’re going to find the cure in there, but some critical observation may be made that says, ‘Ah, here’s something that’s a piece to the puzzle or the beginning of a new, fruitful line of investigation,’” he explained.

As the situation stands now, CHDI won’t shut down any time soon. Researchers, drug companies, academics, medical personnel, and HD families and their supporters will need to keep alive their excellent record of collaboration. If successful, the new drug RG-6042 could be just the first of many needed for HD.

Defeating HD will still “require rolling up our sleeves” and being smart, Dr. Pacifici concluded.

(You can watch my interview with Dr. Pacifici, my recording of Dr. Macdonald’s presentation, and the 2019 CHDI research highlights report, Postcard from Palm Springs, in the videos below.)

The key to Huntington's disease drug discovery ... Collaboration! from Gene Veritas on Vimeo.

Postcard from Palm Springs 2019 from CHDI on Vimeo.

(Next time, Dr. Pacifici explores the question: are we failing to solve HD by ignoring potential “natural” remedies, other alternative therapies, and repurposed drugs?)

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

What if we could turn off the cause of Huntington’s disease?

What if scientists could simply switch off a mutated gene causing a debilitating neurodegenerative disorder like Huntington’s disease?

Known as gene (or genome) editing, that approach is a current hot research topic, generating hope for sufferers of genetic diseases like HD.

Gene editing will be the focus of a symposium on September 4 sponsored by life science start-up incubator Johnson & Johnson Innovation, JLABS (hereafter simplified as JLABS) and the Janssen Pharmaceutical Companies, the drug-discovery arm of Johnson & Johnson, in San Diego, CA.

At the sponsors’ invitation, I will give a presentation, based on my two decades as an HD advocate, on the health and social challenges faced by HD-affected individuals and their families. The two firms have also invited seven leading scientists and biotech executives to speak at the symposium, titled “Science Alliance: Silencing Neurodegenerative Diseases and Sensory Disorders with Gene Editing.”

HD community members can watch the live webcast of the event for free by registering at the event website and entering the discount code “HDCOMMUNITY” at check out. Attendance in person is $35 for the general public and $20 for students and academics, at the JLABS facility at 3210 Merryfield Row, San Diego.

Recent milestones in gene therapy “have ignited interest” in the field and “especially its application to neurological disorders,” the website states. Gene editing has opened the door to innovation in the treatment of diseases like HD, spinal muscular atrophy, and ALS, according to the organizers.

The website points out that, as the technology progresses, key questions are emerging, such as how to effectively deliver gene editing drugs to the brain.

Owned by Johnson & Johnson, JLABS provides labs, offices, marketing, education, and events for early-stage life-science companies unaffiliated with Johnson & Johnson. In San Diego, one of the world’s leading biotech hubs, it offers services to 60 companies; globally, JLABS serves 580 companies.

The pharmaceutical arm of Johnson & Johnson, the Belgium-based Janssen was acquired in 1961.

Advances in gene editing

Gene editing is different from gene silencing, the technique used in the Phase 3 Roche clinical trial currently in progress in the U.S. and a projected 17 other countries (click here to read more). Roche’s RG6042 is an antisense oligonucleotide, an artificial strand of DNA designed block the production of the huntingtin protein in brain cells.

With gene editing, scientists make changes in the actual DNA – a revolution in biomedical research.

The gene-editing technology currently getting the most attention – one already used in the search for HD treatments – is known as CRISPR. Scientists first observed CRISPR occurring naturally in bacteria in the 1990s. In 2002, scientists discovered additional DNA instructions called “Cas.” The combination CRISPR/Cas actually comprises the bacterial immune system. (Click here to read more.)

“There’s no equivalent of word processing software to edit genes,” then Ph.D. candidate Leora Fox (now a Ph.D.) wrote in HDBuzz in 2017. “To fix genes on a microscopic scale, one cell at a time, the faulty code has to be located and physically cut – and that’s what CRISPR/Cas does.”

To alter a gene, scientists need to insert CRISPR/Cas into the cells.

(Image credit: Ernesto del Aguila III, National Human Genome Research Institute, and Wikimedia Commons)

In a disease like HD, the goal is to use this mechanism to cut directly (that is, shorten) the defective, elongated gene. Researchers are also looking at other ways to deploy gene editing.

In recent years, HD research groups have used this technology to edit the HD gene in the brains of genetically modified “HD mice”. One group developed a technique that led to beneficial effects in mice, including the recovery of older mice that had already developed symptoms. (Click here to read more.)

Chinese researchers have used gene editing in human embryos to fix the mutation behind the blood disease beta-thalassemia, which reduces the amount of red blood cells. However, the embryos were not implanted. 

Gene editing is still far from use in human clinical trials. Among the challenges, scientists need to find ways to effectively deliver such a treatment to the brain and avoid inadvertent editing of other genes. (Click here to read more.)

(Late last year a researcher in China claimed to have used CRISPR to alter the genomes of twin baby girls through in vitro fertilization to enable them to resist potential infection from HIV. The news of this development sparked renewed controversy over the use of biotechnology to intervene in human life.)

The symposium participants

To explore gene editing in neurodegenerative and sensory disorders (difficulties with the five senses), JLABS and Janssen have invited seven researchers and executives to the September 4 symposium, including at least two with experience with CRISPR. They include:

Leah Aluisio, Associate Director, Janssen Research and Development;

Alexis C. Komor, Ph.D., Assistant Professor, Department of Chemistry and Biochemistry, UCSD; 

Young Jik Kwon, Ph.D., Professor, Department of Pharmaceutical Sciences, University of California, Irvine, and co-founder, Responsive Polymers Therapeutics, Inc., and Jupiter Therapeutics, Inc.;

Sanjay Mistry, Ph.D., Head of JLABS @ San Diego, Johnson & Johnson Innovation, JLABS;

Gerry Rodrigues, Associate Vice President, Allergan;

Arthur Suckow, Ph.D., CEO, DTx Pharma; and

Gene Yeo, Ph.D., MBA, Professor, University of California, San Diego, and co-founder, Locana and Eclipse Bioinnovations.

Their bios are available on the event website.

Imagining a cure?

As a speaker, I hope to portray HD’s devastating impact and the urgent need for effective treatment.

In the HD world, scientists avoid the word “cure.” HD is so complex that many have said a cocktail of drugs will be needed to target the multiple problems in the brain and elsewhere in the body.

For the first time, actually switching off or completely removing a mutation might enable us to imagine the way to a cure.

Gene Veritas (aka Kenneth P. Serbin) (photo by Yi Sun, Ph.D.)

Factor-H partners with Latin American organizations to aid destitute Huntington’s disease families, seeks to expand support

Looking to aid some of the destitute Latin American families whose critical participation in research led to the discovery of the Huntington’s disease gene, the humanitarian organization Factor-H is poised to seek new funding sources to expand its support in the region.

Founded in 2012 and based in Los Angeles, Factor-H has spent several hundred thousand dollars on projects for and direct aid to poor HD families. 

On July 27 in Los Angeles, Factor-H president and co-founder Ignacio Muñoz-Sanjuan, Ph.D., took part in the world premiere of the short documentary film Dancing at the Vatican, which features South American HD-afflicted families’ remarkable 2017 encounter with Pope Francis at the Vatican.

At the historic Rome event – for which Factor-H played the key role of selecting and arranging logistics for South American families – Francis declared to a global audience of 1,500 HD family members, scientists, and supporters that HD should be “hidden no more.”

Known as #HDdennomore, it was the first time any pope or world leader met with HD-affected individuals.

“It was probably the most significant milestone of what we’ve done,” Dr. Muñoz said in an interview with me on July 29 at the Los Angeles office of CHDI Foundation, the nonprofit virtual biotech focused exclusively on developing HD treatments and where he is vice president for translational biology. “I think it did give us, as an organization, visibility and some credibility that we can do things that are of a certain magnitude.”

The Dancing at the Vatican premiere launched a new fundraising effort by Factor-H. Dr. Muñoz and the film’s producers, including #HDdennomore organizer and Dancing at the Vatican producer and narrator Charles Sabine (like me an HD gene carrier), are seeking to distribute the film widely. In about a year, it will become available online for free. (Click here for my preview.)

Dr. Muñoz holding hand of HD man in South America (Factor-H photo)

‘A very compelling story’

“It’s a very compelling story, very moving, and very positive in its approach,” Dr. Muñoz observed about the film. Viewing it can help people “fully grasp” the extreme poverty and challenges faced by many Latin American HD families.

Dr. Muñoz said Factor-H will use the film to raise awareness about those families’ needs and reach out to donors. “H,” according to the organization, means “hope, humanity, Huntington’s.”

According to Dr. Muñoz, the film captures well “the intersection of disease with poverty and social justice, which I think the HD experience really highlights very well, and I think the documentary does a very good job of highlighting that.”

Dr. Muñoz answering a question at the Dancing at the Vatican premiere (photo by Eddie Sakaki)

Hiring an executive director

Also, Factor-H has received a grant from the Griffin Foundation to hire an executive director, Bianca Moura, to assist with fundraising and media exposure, and to ease the burden on the all-volunteer board by handling day-to-day operations.

The Brazilian-American Moura, who holds a B.A. in development studies from the University of California, Los Angeles, has worked the past 25 years in business leadership positions and as a consultant. She served as board president and executive director for the Miami Beach-based cultural nonprofit Rhythm Foundation.

She will join the Los Angeles-based Factor-H on September 1.

Gene Veritas (aka Kenneth P. Serbin) with Bianca Moura at Dancing at the Vatican premiere (personal photo)

Challenges in Latin America

In recent decades, Latin American countries have generally experienced stronger democracy and rising living standards. However, in the past few years Venezuela has slipped into a deep political and social crisis, causing four million people to flee the country, a record for Latin America.

Also, Latin American societies remain deeply unequal. In many parts of the region, especially outside the developed neighborhoods of the large cities, the social, medical, and governmental infrastructure is poor and sometimes even non-existent.

There is also little knowledge or understanding of HD.

In 2006, as newsletter editor for the San Diego Chapter of the Huntington’s Disease Society of America  (HDSA), I published an article by 2001 HDSA Person of the Year Phil Hardt documenting the private “jails” in which HD-affected people were locked up by ill-informed relatives in the small town of Juan de Acosta in rural Colombia. The town, about 24 miles west of the city of Baranquilla, has the world’s second largest cluster of HD-affected individuals. Hardt works with Factor-H in the implementation of a children’s project in Colombia (see below).

As Dr. Muñoz observed in our July 29 interview, today some HD families lack fresh water and sewage systems. They live in shacks with little or no furniture. Because physicians specializing in neurology and movement disorders like HD also tend to concentrate in the cities, many of the families living in rural areas or in small towns do not have access to specialized care, he added.

In such a setting, families with Huntington’s disease face enormous challenges.

Giving back to poor communities that helped

Visiting such places in Colombia, Venezuela, and elsewhere was a “life-changing experience” for Dr. Muñoz, he told the audience after the screening of Dancing at the Vatican. He saw people from HD families searching for food in the streets, many abandoned children, and young children caring for their HD-stricken parents.

“There is really little chance of a normal childhood,” Dr. Muñoz pointed out. “Many children living with Huntington’s disease or from HD families are discriminated against. Their lives are full of fear and trauma, due to Huntington’s and social exclusion.”

Dr. Muñoz met patients who went years without any kind of medical or social assistance. Others he met eventually committed suicide.

The Lake Maracaibo region of Venezuela, less than 300 miles east of Baranquilla and also on South America’s north coast, has the world’s largest concentration of HD-affected individuals – described by Sabine as HD’s “ground zero.” There pioneering scientist and HD-family member Nancy Wexler’s research, which included collecting blood samples from the people, helped lead to the discovery of the huntingtin gene in 1993. Some villages in the region have as many as 20 percent of their residents living at risk for the disease, Dr. Muñoz observed. 

(The Casa Hogar, a nursing home and clinic in the Maracaibo area for persons living with HD, opened in 1999 thanks to the efforts of Dr. Wexler and a Venezuelan physician, Margot DeYoung.  At present there are no patients living in the Casa Hogar, although outpatient counseling may be available on a limited basis.)

Factor-H wants to “give back” to those and other impoverished HD communities, Dr. Muñoz concluded, issuing an appeal for support.

“At the end of the day, it’s a civil rights issue,” he added in our July 29 interview. “People should have access to fresh water, to decent care, to a bed. Nobody with HD should be dying or in shame or been abandoned by the families, let alone by their governments.”

Supporting basic needs, education, and medical care

As a result, Factor-H has spent several hundred thousand dollars assisting HD families, so far mainly in Venezuela and Colombia, Dr. Muñoz told me in an August 7 e-mail.

Factor-H has focused on helping meet basic needs, arranging for potable water, clothing, medications, specialized medical care, burial services, and legal assistance. It supports the education of children and also of caregivers and patients, including audiovisual materials for the illiterate.

Factor-H also assists with establishing sustainable community development projects to reduce the huge economic burden HD typically causes for families. In the future, it hopes to help establish community centers.

Building a sense of pride for young at-risk people

With its emphasis on children and teens, in 2015 Factor-H established Project Abrazos (“hugs” in Spanish). The program helps children remain in school. The program currently supports 42 Colombian and 100 Venezuelan children ages 5 to 15, all at risk for HD. Factor-H also helps promote sports and recreational activities.

In Colombia, the children also get to vacation during summer and at Christmas “so they have a proper childhood,” Dr. Muñoz said at the premiere. “It’s wonderful to see them doing so much better than when we met them.”

In July 2018, Factor-H co-sponsored the first Latin American Huntington’s Disease Conference in Barranquilla. The conference included activities for Juan de Acosta residents. It was structured to address HD not just as a medical or educational challenge, but also as a social problem, Dr. Muñoz explained.

In tandem with the conference, the Huntington’s Disease Youth Organization (HDYO) organized a meeting for young people from six Latin American countries. For many, it was their first experience of global solidarity and friendship in the HD cause. Factor-H hopes to hold the conference every two years.

Dr. Muñoz described how teens and young people experience the shame, stigma, and social isolation often associated with HD. 

“In many cases, they felt nobody was going to love them and marry them, because they came from an HD family,” he explained in our July 29 interview. “In many instances, I felt that people had no hope that they were going to lead a productive life because they were going to die from Huntington’s, so therefore why go to university and so forth.” 

To overcome this outlook, Factor-H seeks to build a sense of pride, confidence, and growing sense of community in young people, which will help create a new generation of leaders for the Latin American HD community, Dr. Muñoz pointed out. 

Anyervi’s transformation

At the premiere, Dr. Muñoz offered the example of how the life of Anyervi Gotera, 16, of the Maracaibo region, has been transformed by Factor-H and #HDdennomore – despite having learned the day after meeting Pope Francis that he has juvenile HD, in which symptoms appear as early as the toddler years.

Before the pope's arrival in the Vatican auditorium, Anyervi was honored on stage and given a soccer ball and jersey autographed by Brazilian star Neymar.

“When I first met Anyervi a couple years before then, he wouldn’t look at me in the eye,” Dr. Muñoz told the audience. “He was embarrassed, almost ashamed. He didn’t get out of his home in San Luís. He had no friends. He had been pulled out of school because he was being bullied. He usually played alone with a small ball in the back of the house.

“However, today I can say for sure that Anyervi’s story is one of very profound change. He’s adored by his community. He has many friends – his mother would say too many. He’s a very confident teenager, in spite of the disease and because of his speech impediments. In some ways, he has become a hero in his own town.”

Sadly, juvenile HD sufferers like Anyervi rarely live beyond their 20s and often die in their teens. Anyervi’s HD-stricken father, who passed on the gene to his son, died earlier this year. He was in his 40s. 

Juvenile HD-affected Anyervi with soccer ball after #HDdennomore, May 2017 (photo by Gene Veritas)

Establishing trust

In order to understand HD families’ needs, Factor-H also assists with the socioeconomic mapping of HD communities in Latin America. However, Dr. Muñoz stressed that it does not conduct or finance any scientific or clinical research.

Instead, Factor-H aims to form a “trusting relationship” with HD families, he explained in our July 29 interview.

“A lot of the initial experience of impoverished communities with Huntington’s disease with medical or scientific professionals has always been around their participation in a scientific or clinical study,” he said. “So there was a bit of a misperception that I was there as a scientist to study them, which wasn’t the case.

“Our strategy from the beginning was to get to know them as individuals and as a community, understand their history, understand their needs, and also identify local organizations or community leaders who we could work with to channel help and be able to implement projects to their benefit.”

Thus, Factor-H partners with local HD associations, foundations and nonprofit organizations, universities and medical schools, aiming to maintain full transparency, for example by holding public meetings, Dr. Muñoz said.

(Though #HDdennomore indicates progress, the Catholic Church has offered limited and sporadic assistance so far, but Dr. Muñoz said he believes more help may be forthcoming. Recently, Factor-H received a small grant from the Italian branch of Caritas, the Catholic international aid agency.)

Local HD groups and families need “to be involved at every step of the way,” Dr. Muñoz said. “We don’t want to be an organization that comes in from outside to tell people what they need to do.” 

Factor-H and its partners seek to raise awareness regarding HD among Latin American governmental and nongovernmental organizations, then stress the need to assist affected families with specialized support, Dr. Muñoz explained.

Expanding across Latin America – and beyond?

According to Dr. Muñoz, in addition to Venezuela and Colombia, Factor-H has also pursued projects in Chile and Peru. It brought an Argentine family to #HDdennomore and has also done fundraising in that country, and it involved Brazilians in the 2018 HD conference in Colombia. Factor-H has also received inquiries from Ecuador and Costa Rica.

Factor-H would like to extend to all of Latin America, Dr. Muñoz said.

In Brazil alone, Latin America’s largest country (and the world’s fifth largest) with 210 million people, an estimated 20,000 people have HD. (Dr. Muñoz visited a poor, isolated HD community there in 2013.) Mexico, the world’s eleventh largest country, also doesn't yet have Factor-H programs.

Indeed, HD organizations, even in rich countries, have been able to afford family and community assistance at best only on a small scale.

WeHaveAFace offers a small family assistance program currently operating in Canada, but the U.S. branch is currently out of funding, Kevin Jess, the WeHaveAFace Canada vice president, told me in an August 9 Facebook interview.

HDSA and its National Youth Alliance provide scholarships to its annual conventions, but have no family assistance program. However, as HDSA CEO Louise Vetter explained in a phone interview August 12, the organization keeps the HD community informed of other assistance programs such as the Thomas Cellini Huntington’s Foundation and Healthwell Foundation’s fund to help with HD medications.

HDSA assisted Factor-H with #HDdennomore, the shooting of the footage for Dancing at the Vatican, and the Los Angeles premiere, Vetter said. It has also helped Factor-H with project management.

“It’s part of our responsibility to the global community that we make sure that all families affected with HD have access to the best information and best resources,” she said, adding that HDSA is also “very active in international partnerships and collaborations” with HDYO, the International Huntington Association, the European Huntington Association, and HD Cope.

Noting that the Factor-H is applicable anywhere, Dr. Muñoz believes that it could someday set up elsewhere in the developing world. 

“Any family with Huntington’s that’s living in difficult situations socially or financially, if we can help, we should be able to help,” he said.

For any of this to happen, he added, Factor-H needs broader support among both individuals and institutions.

Watch my July 29 interview with Dr. Muñoz in the video below. Just below that video, watch our additional interview in Spanish about Dr. Muñoz’s scientific background and research, Factor-H, and the progress towards HD treatments.