Hacking humans, upgrading Homo sapiens: the role of the Huntington’s disease community and the consequences for life

An influential book by best-selling historian Yuval Noah Harari, Homo Deus: A Brief History of Tomorrow, looks broadly at potential medical advances, thus providing hope for the Huntington’s disease community’s quest for a cure, but it also warns of the vast consequences for human life caused by the advance of biotechnology and the accumulation and control of data.

A professor in the History Department at the Hebrew University of Jerusalem and holder of a Ph.D. from the University of Oxford, England, Dr. Harari published the international blockbuster Sapiens: A Brief History of Humankind. Sapiens was first published in Hebrew in 2011 and was translated into nearly 50 languages, selling over 10 million copies by 2018.

In Sapiens, Dr. Harari uses macro-history (also known as “big history”) and biological evolution to explain the development of human society over the past several hundred thousand years. He focuses in particular on the “cognitive revolution” that began 70,000 years ago. During this period, the modern human species, Homo sapiens, came to dominate Earth.

“Homo sapiens” is Latin for “wise man.” “Deus” means “god.” In Homo Deus, first published in English in 2016, Dr. Harari projects current trends deep into the 21st century and speculates that humanity could double average life expectancy to 150 years. He also considers the profound changes longer lives would bring such as people in positions of authority stretching out their careers and thus cutting off opportunities for younger individuals.

Ultimately, in this century humanity may seek immortality by developing new biomedical tools and implants, fusing our bodies with high-tech machines, and perhaps also creating non-organic beings.

“You may debate whether it is good or bad,” Dr. Harari writes, “but it seems that […] the twenty-first century will […] involve re-engineering Homo sapiens so that it can enjoy everlasting pleasure. In seeking bliss and immortality humans are in fact trying to upgrade themselves into gods. Not because these are divine qualities, but because in order to overcome old age and misery humans will first have to acquire godlike control of their own biological substratum [bedrock].”

A new scientific dogma: we are algorithms

The idea of ending disease and extending life, even if by only a few years, stirred the depths of my being. The fear of death propels our psyches and civilization. In the Huntington’s community, where the disease’s devastating and fatal symptoms cut off down lives early, the fear of death is ever-present and more acute. I recalled my mother’s death from HD in 2006 at 68 and my condition as an HD gene carrier. At 59, each day without symptoms is a blessing.

Homo Deus also reminded me of my 2010 article “God, Huntington’s disease and the meaning of life,” in which I examined the Catholic Church’s little-known and little-understand acceptance of evolutionary theory and the notion that the Resurrection of Christ could be seen as a genetic mutation.

However, in Homo Deus Dr. Harari also warns that current trends in biotechnology and the gathering and control of data could also lead to the creation of a super-human elite taking control of the rest of humanity, threatening privacy, democracy, and human and civil rights.

“If indeed we succeed in hacking and engineering life, this will be not just the greatest revolution in the history of humanity,” Dr. Harari told the audience at the 2018 World Economic Forum Annual Meeting in Davos, Switzerland. “This will be the greatest revolution in biology since the very beginning of life 4 billion years ago.[…]

“Science is replacing evolution by natural selection with evolution by intelligent design. Not the intelligent design of some god above the clouds, but our intelligent design, and the intelligent design of our clouds, the IBM cloud, the Microsoft cloud. These are the new driving forces of evolution.”

Yuval Noah Harari in 2017 (photo from Wikimedia Commons)

In Homo Deus, Dr. Harari explains that “science is converging on an all-encompassing dogma, which says that organisms are algorithms” – a method or list of instructions for making calculations – “and life is data processing.”

“Humans are algorithms that produce […] copies of themselves,” he adds. The influence of computer algorithms designed by organizations such as Google has grown vastly, taking in fantastic sums of personal data for users of the Internet and personal devices. “Non-conscious but highly intelligent algorithms may soon know us better than we know ourselves.”

In their digital lives, over 2 billion Facebook members have encountered that organization’s problematic algorithm, which a company study found to be a better reader of people’s personalities than even their friends, parents, and spouses, Dr. Harari points out.

Crucial data from HD families

Homo Deus doesn’t mention HD. However, it recognizes the importance of Alzheimer’s disease and the need to prevent it and disease in general. Dr. Harari explains that upgrading humanity would include attempts to expand the abilities of the brain – which, of course, is an organ severely debilitated by HD.

The history of the search for HD treatments is key to the biotechnological revolution. HD-affected individuals and their families have both witnessed and participated in that revolution, starting with the hunt for the huntingtin gene in the 1970s, 1980s, and 1990s, and since then with a growing number of research studies and clinical trials involving thousands of individuals.

At the start of this decade, CHDI Foundation, Inc., the nonprofit virtual biotech focused on defeating HD, pioneered the use of systems biology, which includes the deciphering of vast amounts of biological data, in disease treatment (click here to read more).

CHDI has also collaborated with IBM to seek deeper understanding of the huntingtin protein’s role in the disease. In this effort, IBM has provided its immense computational power and the tools of big data analytics.

Enroll-HD, the CHDI-sponsored worldwide database of HD-affected individuals and family members, has more than 17,000 participants. Thousands of HD-affected individuals and gene carriers have also participated in the research involving the search for so-called modifier genes that affect the age of onset. The scientists have analyzed millions of small variations in these people’s genes.

Digital monitoring and algorithms

An increasing number of researchers and companies are in effect trying to hack HD’s genetic causes. The most prominent is the gene-silencing drug developed by Ionis Pharmaceuticals, Inc., in collaboration with CHDI and other researchers. On December 19, pharma giant Roche, now the drug’s license-holder, announced the first 26 planned sites for the crucial global Phase 3 trial to test the drug’s efficacy.

In that trial, participants will receive the drug via lumbar puncture (spinal tap), the first time this delivery method is being used extensively in an attempt to treat a neurological disorder.

For the study, Roche has designed an HD Digital Monitoring Platform, which will continually measure participants’ biometric data using smartphones and watches.

“The software is what’s special, and the analytics engine behind it,” Erik Lundgren, the Roche lifecycle leader of the HD team, said in an interview last March. “A tremendous amount of data comes in. The algorithms and how you make sense of that is what our team has been working hard on developing.”

A graphic illustrating the Roche HD Digital Monitoring Platform (source: Roche)

Privacy versus healthcare systems

As Dr. Harari warns, the purpose and uses of technologies and information-gathering techniques originally developed for something positive such as curing a disease could result in unintended, perhaps negative, consequences.

Companies such as Google “want to go much deeper than wearables,” he explains.

“If we give Google and its competitors free access to our biometric devices, to our DNA scans and to our medical records, we will get an all-knowing medical health service that will not only fight epidemics, but will also shield us from cancer, heart attacks and Alzheimer’s,” he writes.

However, he observes, “imagine a system that, in the words of the famous Police song, watches every breath you take, every more you make and every bond you break; a system that monitors your bank account and your heartbeat, your sugar levels and your sexual escapades. It will definitely know you much better than you know yourself.”

Google and these other algorithm-based systems could make decisions for us, from selecting which movie to watch to choosing a spouse to settling on a candidate in the voting booth.

In a world in where the stress on data takes on a religious fervor, the demand for the free and massive flow of information could trump freedom of expression and, by extension, people’s right to control their own information, Dr. Harari asserts. He cites pressure from “Dataist missionaries” for free access to all information, including copyrighted materials.

The danger is that “we will just have to give up the idea that humans are individuals, and that each human has a free will determining what’s good, what’s beautiful and what is the meaning of life.” 

“The big battle over what we today call ‘privacy’ will be between privacy and health,” Dr. Harari asserted at the World Economic Forum. “Do you give access to what is happening inside your body and brain in exchange for far better health care? And my guess is that health will win, hands down.[…] Maybe in many places [people] won’t have a choice. They won’t get insurance if they are unwilling to give access to what is happening inside their body.”

What kind of world are we creating?

Because of the many critical issues it touches on regarding humanity’s future, Homo Deus is a must-read book.

For the HD community, it provides valuable context for the difficult medical, social, and ethical challenges involved in the disease and the quest for treatments.

As many in science strive, in Dr. Harari’s words, to “defeat death and grant humans eternal youth,” the complexities of HD and the close collaboration between HD scientists and families may serve as a reminder that the biotechnological and medical sectors should consult disease communities and the rest of society.

Yes, despite having back problems, to avoid HD onset I would take a drug via recurring spinal taps. I would also wear a data monitor, as do people with type 1 diabetes, for example.  

However, I’m also concerned about the dystopian scenarios outlined by Dr. Harari for this century.

What kind of world are we creating for our children and grandchildren?

Can we afford the costs of orphan disease treatments?

Millions of people in America suffer from rare, or “orphan,” diseases, conditions defined by the government as affecting fewer than 200,000 people. With an estimated 30,000 affected individuals, Huntington’s disease is one of the more common of these disorders.

The pharmaceutical industry has largely ignored these diseases, which number several thousand, because each disease promises too few customers/patients to enable companies to recoup investments in drug research and development and therefore generate a profit. The market usually doesn’t work for people with these diseases.

News about a lawsuit by Arkansas cystic fibrosis (CF) patients against the state’s Medicaid program for its refusal to pay for a highly effective but extremely expensive drug – Vertex Pharmaceutical’s Kalydeco – shined light on this predicament.

In an article titled “The $300,000 Drug,” New York Times columnist Joe Nocera recognized Kalydeco as a “wonder drug” but questioned whether the country can afford the personalized medicine approach that enables scientists to design specialized treatments for very small and specific groups of patients.

With an annual wholesale cost of $311,000, Kalydeco was developed for a subgroup of about 1,100 CF patients with specific genetic mutations. The subgroup numbers about 2,150 patients worldwide in an overall CF population of 70,000 individuals.

“Because patients will likely be taking the drug for the rest of their lives, it could cost millions of dollars to keep just one patient on Kalydeco,” Nocera speculated. “That raises another important question about the coming of personalized medicine. How are we, as a society, going to pay for it?”

Same question for the HD community

The HD community could face this very same question. Because the U.S. has only 30,000 HD patients and 150,000 to 250,000 people at risk of carrying the gene, a potential treatment could cost a lot.

Boston-headquartered Vertex has sought to develop HD treatments since mid-2008. Though the company has made a substantial effort, it doesn’t yet have plans for a clinical trial. (Click here to read more.) Isis Pharmaceuticals, Inc., of Carlsbad, CA, has also worked about as long and is planning to launch a clinical trial in the next year or two.

It’s still too early to project the costs of treatments that have yet to be tested or even fully designed. Other potential remedies are in trials but at best likely remain years from reaching the market.

Furthermore, an HD treatment regimen will likely involve a cocktail of remedies, meaning that patients – via their insurers – will probably have to pay for more than one drug.

Vertex vice president of research Paul Negulescu (left), Gene Veritas (aka Kenneth P. Serbin), and Vertex vice president of biology Beth Hoffman at the company's San Diego facility, September 2010 (photo by Heather Farr, Vertex)

Patient assistance programs

The HD community must remain vigilant regarding the cost of potential treatments. However, failing to consider a number of factors, the coverage of the Kalydeco costs was perhaps too pessimistic about the future.

First, as I commented regarding the impatience with California’s stem cell institute after ten years of operation without a drug, biomedical research is slow by nature. And it’s expensive, with the average cost of developing a new drug in the U.S. at $1.2 billion. Only one in ten clinical trials results in a marketable drug, although the research from the unsuccessful projects provides highly valuable information on what does not work.

In the case of CF, Vertex is at work on another treatment that would reach thousands more patients with different kinds of mutations.

As Nocera himself noted, Vertex provides Kalydeco for free to patients without insurance.

Lundbeck, the pharmaceutical firm that markets Xenazine, which diminishes some of the involuntary movements caused by HD (chorea), provides financial assistance to patients who qualify. Depending on the dosage, the annual wholesale cost of this treatment can reach $50,000 or more, but, according to the Lundbeck website, “85 percent of U.S. patients taking Xenazine have a monthly co-pay of $50 or less before requesting co-pay assistance.”

It’s highly conceivable that the developers of future HD treatments will provide similar kinds of assistance – especially because these firms will have relied on the good will and extensive cooperation of HD families who participate in research studies and clinical trials. However, it’s not clear what the drug companies will charge insurers.

CHDI and pharma giants

After the founding in 2003 of the CHDI Foundation, Inc., a non-profit virtual biotech firm backed by wealthy donors who wish to remain anonymous, pharmaceutical firms small and large started to gain interest in developing Huntington’s treatments.

As a result, the network of firms working on HD now includes pharmaceutical giants such as Pfizer, Roche, and Medtronic.

As a non-profit with the sole purpose of finding HD treatments, CHDI promotes research on Huntington’s and the diffusion of scientific knowledge about the disease. With more researchers and firms involved, the chances for treatments have grown. Having more options could very well mean that treatments would cost less.

By pouring hundreds of millions of dollars into HD drug research, CHDI has created an incentive to produce cheaper drugs.

As it states on its website, CHDI seeks to connect academic research, drug discovery, and clinical development in order to avoid “costly delays to therapeutic development” and make potential treatments a “good investment” that will result in “full clinical development, including licensure and marketing to get drugs to HD patients.”

Similarly, the Hereditary Disease Foundation and the Huntington’s Disease Society of America (HDSA) have supported research that could yield yet additional drugs.

Patient-driven medicine

Thanks to this level of support for HD research, the HD community stands in perhaps a better position than those facing even more rare diseases.

Nevertheless, orphan disease communities in general have reason to feel optimistic about both the development of treatments and their cost, if the vision of one key medical leader becomes reality.

Lee Hood, M.D., Ph.D., one of the scientific giants behind the Genome Project and the recipient in 1987 of the Lasker Basic Medical Research Award (the American equivalent of the Nobel Prize), has developed a plan for more effective and affordable medicine. In 2000, Dr. Hood founded the Institute for Systems Biology (ISB). Located in Seattle, the non-profit ISB teams scientists and technologists from many disciplines to pioneer the future of research in biology, biotechnology, medicine, environmental science, and science education.

In a 2012 speech at the Seventh Annual HD Therapeutics Conference, sponsored by CHDI, Dr. Hood outlined the importance of systems biology – what I think of as the “big picture” of disease – for HD research. Dr. Hood also advocated for the adoption of P4 medicine: predictive, preventive, personalized, and participatory. (Click here to read more.)

“Patients and consumers will be a major driver in the realization of P4 medicine through their participation in medically oriented social networks directed at improving their own healthcare,” Dr. Hood and Mauricio Flores, J.D., wrote in the March 2012 issue of the journal New Biotechnology.

ISB and several collaborating organizations have run some pilot programs in P4. If it is implemented on a wide scale, Dr. Hood predicts that it will revolutionize our healthcare system. Everybody will carry a health-monitoring device, and diseases will be predicted and prevented long before onset as the result of tiny blood samples taken from a pin prick, the article states.

Predicting falling medical costs

Significantly, costs could plummet.

“P4 medicine will require that all healthcare companies rewrite their business plans in the next 10 years or so,” Dr. Hood and Flores wrote. “Many will not be able to do so and will become ‘industrial dinosaurs.’ There will be enormous economic opportunities for the emergence of new companies tailored to the needs and opportunities of P4 medicine.”

The authors projected that savings will result from a series of factors, including earlier and more effective diagnosis of disease; better matching of drugs with diseases and their subtypes; better identification of genetically based adverse reactions to drugs; the ability to “re-engineer” disease-affected biological networks within people in order to reduce the cost of drug development; an increasing ability to deal effectively with cancer; the use of stem cells for replacement therapy and diagnostics; the routine extension of effective mental and physical health into people’s 80s and 90s; an improved understanding of microbes in the body; a deeper understanding of neurodegeneration (the cause of HD, Alzheimer’s, Parkinson’s, and other disorders); and the digitalization of medical and genetic information.

“On another tact, our prediction is that there will be a ‘wellness industry’ that will emerge over the next 10-15 years that will in time far exceed the size of the healthcare industry,” Dr. Hood and Flores affirmed. “P4 medicine is an area replete with economic opportunities.”

Dr. Hood and Flores believe that P4 medicine will “democratize” healthcare.

“The patient (consumer), through social networks, will drive the emergence of P4 medicine,” they wrote. “Because of intrinsic conservatism and sclerotic bureaucratic systems, physicians, healthcare specialists and the healthcare industry will take a back seat to the power of patient-driven social networks in bringing change to the healthcare system. Indeed, patients may be the only driving force capable of truly changing our contemporary healthcare system to the proactive P4 mode.”

This scenario serves as a serious alternative to the dim view that orphan disease communities will remain relegated to high-cost solutions.

Guaranteeing proper care standards

Indeed, a “revolution” has occurred over the past two decades in how patients have related to their doctors and the pharmaceutical industry (click here to read more).

Nowadays, people enter the healthcare system as both patients and advocates for their well-being.

This outlook led the Arkansas patients to sue for the right to have their Kalydeco costs covered.

Their lawsuit offers a striking similarity with the HD community’s pressure on the Social Security Administration and Congress to update the decades-old, inaccurate government criteria for determining disability benefits for Huntington’s patients (click here to read more). The Arkansas plaintiffs in effect have demanded that the state recognize Kalydeco as the standard treatment for their type of CF.

Negotiating the price

The competition of the marketplace, greater efficiency in drug development, and the revolution in medicine outlined by Dr. Hood should put downward pressure on the cost of drugs.

Patient advocates must play a crucial role in this process.

As the late San Diego biotech leader Duane Roth had told me during a dinner with California stem cell leaders in 2008, patient advocates must find ways to appeal to pharmaceutical companies’ primary interest in profits. Advocates need to lobby and court these business leaders.

At the same time, disease organizations such as HDSA and its network of advocates can pressure pharmaceutical companies and government agencies to assure new drugs’ accessibility and affordability.

In some circumstances, government can join in the process of persuasion and even play hardball, as the Brazilian Ministry of Health did in the 1990s in order to convince multinational pharmaceutical firms to dramatically reduce the price of HIV/AIDS medications. The Brazilian government provides HIV/AIDS drugs for free.

“Local production of generics, the possibility of breaking patents, and the offer of technology transfer became instruments for price negotiations with other countries and the pharmaceutical industry, leading to a real reduction in prices on the Brazilian and international markets,” wrote the coordinator of the country’s National STD/AIDS Program.

The marketplace exists, but it is susceptible to politics.

The rhetoric about the $300,000 drug can scare a lot of people. But in the long run, such a cost is not a foregone conclusion.

‘It’s really getting real’: payoffs in the effort to treat Huntington’s disease

The path to treating Huntington’s disease – a potential major breakthrough in the history of science and medicine – is becoming clearer.

That was the takeaway message from the Ninth Annual HD Therapeutics Conference, organized by the CHDI Foundation, Inc. and held February 24-27 at the Parker hotel in Palm Springs, CA. Spending tens of millions of dollars annually, CHDI is a non-profit, virtual biotech founded solely to discover HD treatments. Some 300 participants from academia, the pharmaceutical industry, and biotech firms took part, as well as a number of patient advocates, including Olympic rowing medalist Sarah Winckless, who delivered the keynote address.

“The tagline would have to be ‘it’s really getting real,’” said Robert Pacifici, Ph.D., the chief scientific officer for CHDI Management, Inc., in an interview with me at the conference. “What I’m seeing at this conference already is the culmination of very large, very long-term efforts – things that have taken years and thousands of person hours, patients’, caregivers’, researchers’, and physicians’ – finally coming together in ways that are really conclusive and really helpful.”

All that work has involved numerous questions about the disease and potential ways to treat it, Dr. Pacifici explained.

“All of those things sadly have an incredibly high attrition rate,” he observed. “The fact that we’re getting answers is the thing that makes me the most excited. Sadly, sometimes we don’t like the answer. Sometimes the answer is: ‘That doesn’t work.’ But that’s still very useful for researchers.”

Winnowing out the useless approaches allows researchers to “refocus our resources on something that we feel has a better chance of bearing fruit,” Dr. Pacifici said.

Sitting one evening with a group of CHDI researchers, I expressed the natural concern of the HD community – a concern sometimes tinged with impatience and frustration: could the rapidly expanding knowledge about HD result in an endless search for treatments fueled by questions that simply produce new questions rather than treatments?

They answered with an emphatic no. Echoing Dr. Pacifici, they said that real solutions were in the works.

The conference did seem more coherent in comparison with the previous three I had attended. Indeed, as one senior CHDI advisor observed in response to my observation, Huntington’s researchers now have an understandable “story to tell” about the disease and the research.

You can watch my interview with Dr. Pacifici in the video below. Just below the Pacifici interview, Portuguese speakers can watch my interview about the conference with Dr. Mônica Haddad of Brazil.

'It's Really Getting Real': Payoffs in the Effort to Treat Huntington's Disease from Gene Veritas on Vimeo.

A esperança de tratar a doença de Huntington: Dra. Mônica Haddad fala sobre a conferência da CHDI from Gene Veritas on Vimeo.

Confirming the shots on goal

Just three days before the conference, CHDI and Genzyme Corporation announced an agreement to jointly develop a “novel gene-silencing therapeutic for Huntington’s disease” using an adeno-associated virus, which does not cause disease, as a delivery system.

The venture expands CHDI and other research projects’ portfolio of potential treatments for HD, several of which are in the early stages of clinical trials or aim to begin trials soon.

In Dr. Pacifici’s words, the growing number of drug targets means there are more “shots on goal” in the quest for treatments.

CHDI is concentrating on “validating” (confirming) the targets to assure that as many potential remedies as possible have a chance of becoming effective, safe treatments, Dr. Pacifici explained.

“It’s important for any drug discovery organization, because when you select a target, that’s what underpins the rest of the (drug discovery) activity,” he said.

No organization has yet discovered how to validate targets “exactly,” he said. However, CHDI is especially working hard to insure that a “particular target is really tethered” to the HD disease process and not some other disease or process, he added.

“While nobody has the magic bullet there, it was really impressive to see the variety of approaches that were taken,” Dr. Pacifici said of the talks on target validation.

These included X. William Yang’s report on his latest research with transgenic HD mice, Ernest Fraenkel’s study of the impact of the mutant huntingtin gene at the molecular level, and CHDI scientist Jim Rosinski’s efforts to unify and interpret the totality of biological data on HD by employing a systems biology approach.

You can watch an excerpt from Dr. Fraenkel’s presentation, Dr. Rosinski’s full presentation, and most of the other talks by viewing my 2014 CHDI video album.

Finding a modifier gene, delaying onset

Jim Gusella, Ph.D., one of the lead discoverers of the HD gene in 1993, described the work of a large international team to find a so-called modifier gene, which might act as a trigger for the disease and affect the rate of progression.

Such a gene could also become the target of a treatment, Dr. Pacifici explained.

“Imagine coming up with a drug that can delay your age of onset by 30 years,” he said, referring to the wide variability in age of onset for people with the same degree of mutation. “That would be fabulous.”

The Gusella team’s search for the modifier gene points to “a couple of specific sites on human chromosomes,” Dr. Pacifici said. In contrast with the numerous studies done in mice and other organisms, this project “was generated with human data. So we don’t have to worry about the predictive value of those studies.”

Dr. Pacifici described the 20-year quest for the modifier gene as “a great example of how the community pulls together and the generosity of the families affects the progress of research. Without your blood, without your DNA sequences, without your permission, there’s no way these types of studies could be done.”

The team analyzed DNA from more than 4,000 HD gene carriers and affected individuals. The study also required the ongoing commitment of participants to allow researchers to track their symptoms.

“We need to make the correlation as to when the motoric age of onset (the start of involuntary movements) occurred,” Dr. Pacifici explained. “That’s invaluable and incredibly appreciated. Hopefully now people can understand why participation in trials like this leads to such exciting discoveries.”

New potential therapies

A session on “novel therapeutic approaches” focused on potential remedies different from the traditional concept of oral medication.

Jan Vesper, M.D., presented the promising results of his pilot trial using deep brain stimulation, which involves the placement in the brain of metal capsules covered with electrodes. Long-time HD specialist Gill Bates, Ph.D., discussed her new research on the muscle deterioration involved in HD mice and the potential use of a myostatin inhibitor to remedy the problem as well as perhaps ameliorate the involuntary movements typically suffered by patients.  Beth Stevens, Ph.D., explained the importance of restoring proper function of microglia (cells performing as the immune system of the nervous system) in pruning synapses, the connections between brain cells.

‘A horrible, lifelong case of jet lag’

Changes in people’s behavior could provide another way to ameliorate HD, Dr. Pacifici noted.

Along those lines, Christopher Colwell, Ph.D., presented critical new research on the circadian rhythm – our sleep clocks – and how its disrupted function in HD might worsen symptoms.

“Think of Huntington’s almost as a horrible, lifelong case of jet lag,” Dr. Pacifici said in describing the implications of Colwell’s and others’ work in this area. “By entraining (synchronizing) the clocks in your mind and the clocks in your various organs to stay in sync with each other – by using things like when you eat, when you go to sleep, when you exercise, what kind of light you’re exposed to – you could compensate for some of the mechanisms that go awry in Huntington’s disease. That type of regimen could be a therapy, or an add-on to a therapy, rather than something as traditional as a pill.”

Dr. Colwell’s engaging talk provided a wealth of ideas about the circadian rhythm and keeping it healthy. You can watch his presentation in the video below.

Circadian disruptions in Huntington's disease: mechanisms and possible treatment options from Gene Veritas on Vimeo.

Alpar Lazar, Ph.D., Stephen Morairty, Ph.D., and Tom Warner, Ph.D., provided additional evidence about the importance of the sleep cycle.

Assuring the drug does its job

In the session on “huntingtin lowering biomarkers,” several presenters described cutting-edge techniques for measuring the efficacy of potential therapies designed to attack HD at its genetic roots and reduce the effects of the mutant huntingtin protein. Those projects include the above-mentioned CHDI-Genzyme venture and the Isis-Roche-CHDI partnership.

“What you’d like to do is make sure that after you administer one of those drugs, that the drug has done its job,” Dr. Pacifici explained. “We don’t want to wait for five years to measure hundreds of people only to find out that the drug never did its primary job, which was to lower huntingtin levels.”

Along with an expert task force, CHDI has developed a series of ways to determine huntingtin-lowering efficacy in humans within a period of weeks, he said.

“Because we want to know what’s going on in the human brain, and we can’t go in there and take a little chunk of brain out every couple of weeks, we have to figure out a way of non-invasively making those measurements,” Dr. Pacifici continued.

The techniques include quantitative EEG (a kind of brain mapping), magnetic resonances pectroscopy, assessment of dysfunction in the mitochondria (the powerhouses of the cell), and measurement of huntingtin in bodily fluids such as cerebral spinal fluid.

Scientists are developing ways to measure other types of potential HD remedies such as phosphodiesterase inhibitors (aka “Viagra for the brain”).

As the HD field moves towards clinical trials, CHDI has increasingly emphasized the need for the exchange of information between scientists in the lab and physicians and others focused on patients and clinical trials, Dr. Pacifici commented. Such teamwork will enhance the possibility of finding treatments, he said.

Supporting Enroll-HD

The conference also featured several activities promoting Enroll-HD.

First announced in 2010 and officially launched in 2012, the CHDI-sponsored Enroll-HD is building a worldwide registry of HD patients, HD gene carriers, untested at-risk individuals, family members, and volunteers. It aims to facilitate scientific understanding of HD, identify potential participants in clinical trials, and therefore speed the process of finding therapies.

In a pre-conference meeting of Enroll-HD physicians and administrators on February 23, participants focused on ways to use the project to improve patient care. On February 24, Enroll-HD’s international steering committee met to discuss administrative matters.

On February 25, the CHDI conference featured a practical lunchtime session that provided an update on program details like the number of participants.

A ‘matchmaker’ facilitating clinical trials

In order to deepen understanding of Huntington’s, Enroll-HD looks at individual and family histories of HD “over a long period of time,” Joe Giuliano, CHDI’s director of clinical operations and the chief Enroll-HD administrator, said in an interview on February 24.

“The vision for Enroll-HD is to provide a clinical research platform that can be used by the community of HD researchers around the world to do clinical studies, and it can be used by pharmaceutical sponsors to do clinical trials,” Giuliano explained. “It’s an enabling tool to help answer important questions about Huntington’s disease using clinical research.”

Giuliano described the program’s three levels: the international administration, the wide range of sites based in local communities (run by physicians and other health workers), and the HD families.

“It starts with families,” Giuliano said. “Enroll-HD is really a study for all the family to participate in.

“Enroll-HD is a great opportunity for us to come together as a global research community. The clinical trials that are going to lead ultimately to new therapies for Huntington’s disease are going to be conducted in global clinical trials…. The more people we can get in Enroll-HD, the more powerful the study can become, for example, for recruiting for clinical trials. Enroll-HD can help identify participants … who are eligible for clinical trials.”

This potential makes Enroll-HD “very attractive” for pharmaceutical companies to collaborate with the program, Giuliano said.

Enroll-HD is a “matchmaker” putting together researchers, patients, drug companies, and others, he continued.

Anybody in the HD community can participate, including unaffected relatives of HD people. “By joining Enroll-HD, you’re being very proactive in a lot of different ways,” he said. “You’re providing the possibility that you may be eligible for a future clinical trial.”

The larger the pool of potential participants, the faster trials can take place, he concluded.

You can watch my interview with Giuliano in the video below.

For other coverage of the conference, visit www.HDBuzz.net.

Coming soon: a detailed report and more videos on Enroll-HD.

What is Enroll-HD? An interview with Joe Giuliano from Gene Veritas on Vimeo.