Another major supplement, creatine, proven ineffective in the fight against Huntington’s disease

For the second time in less than three months, a widely taken and long-studied dietary supplement envisioned as a potential treatment for Huntington’s disease has been proven ineffective, bringing a halt to a clinical trial.

Creatine, a supplement popular among body builders and readily available in health food stores, was studied in a clinical trial called CREST-E (Creatine Safety, Tolerability, and Efficacy in Huntington’s Disease), which began in 2009 and was to be completed in 2016.

On October 29, the National Center for Complementary and Alternative Medicine, part of the National Institutes of Health (NIH), announced that it was discontinuing CREST-E because a preliminary analysis of the data “showed with high confidence that it was unlikely that the study would be able to show that creatine was effective in slowing loss of function in early symptomatic Huntington’s Disease.”

The study was carried out by the Huntington Study Group (HSG) and led by Dr. Steven Hersch of Massachusetts General Hospital and Dr. Giovanni Schifitto of the University of Rochester School of Medicine.

“The entire point of the CREST-E study was to determine whether creatine slows the course of HD or not, and the answer is, no, it does not,” Martha Nance, M.D., a member of the HSG executive committee, said in an e-mail. “Although this result is disappointing, it is still important, as it gives us a definite answer to the question: ‘I have HD. Should I take creatine?’ The answer is, ‘no.’”

“I recommend that all stop taking creatine,” Dr. LaVonne Goodman, the founder of Huntington’s Disease Drug Works (HDDW), said in an e-mail.

False hopes

Huntington’s disease typically reduces people’s energy levels. Scientists thought that creatine, which cells use to store energy, might help compensate for the energy deficit in brain cells and enable them to survive.

Positive results in animal studies regarding the impact of creatine, the rise of HDDW’s “treatment now” program ten years ago, and the advent of both CREST-E and a companion study in presymptomatic individuals known as PRECREST led to much discussion about the supplement in the HD community.

Many people have taken or considered taking creatine in the hopes of avoiding or ameliorating symptoms.

I have taken creatine for about ten years, beginning with my participation in the HDDW program.

Just after receiving the news about CREST-E yesterday, I received an e-mail from an individual inquiring about where to purchase creatine and what amount to take. I responded that “it is now recommended that nobody take creatine.”

HDBuzz.net also reported on the end of CREST-E, calling the new evidence against creatine “compelling.”

Awaiting HD-specific remedies

In mid-August, the National Institute of Neurological Disorders and Stroke and the HSG stopped a clinical trial for coenzyme Q10, another widely taken supplement.

I outlined my approach to HD supplements and the pros and cons of the matter in a February article titled “To take, or not to take, unproven supplements in the fight against Huntington’s disease.” That article also reported on the hopes for PRECREST and CREST-E.

With the elimination of both coenzyme Q10 and creatine in rapid succession, the HD community is suddenly left without two potential treatments that supplied significant  hope.

However, supplements lack what researchers refer to as HD-specific approaches to treatments. They were not designed or marketed with HD in mind, whereas the new treatments currently under study will potentially attack the specific causes of Huntington’s.

Hope for effective treatments is on the rise as researchers and pharmaceutical firms gear up for new clinical trials such as the Isis Pharmaceuticals, Inc., gene-silencing approach announced for the first half of 2015.

“The important thing right now is to learn from ‘negative’ outcomes like this,” the HDBuzz article observed. “Studies like CREST-E have helped us, as a community, to get really good at designing, enrolling and running clinical trials, and understanding why particular treatments don’t work. Now we have the result of CREST-E, all that energy, enthusiasm and experience can be directed into testing other experimental treatments with a higher chance of success. One very solid benefit is that hundreds of volunteers are now freed up to sign up for other clinical trials enrolling now or in the near future.”

For the latest news on HD research and clinical trials, watch the video below for the update by Jody Corey-Bloom, M.D., Ph.D. (Note that the talk took place on October 27, before the announcement about creatine.)

2014 Huntington's Disease Research Update: A presentation by Dr. Jody Corey-Bloom from Gene Veritas on Vimeo.

The dire need for neurological treatments

I am now rethinking my approach to supplements. I have stopped taking coenzyme Q10.

I agree with the doctors’ recommendations to halt creatine. My breakfasts and dinners will no longer include a heaping teaspoon of fruit-flavored creatine dissolved in a glass of water.

Container with over-the-counter creatine (photo by Gene Veritas)

I will discard my remaining supply of creatine but keep the container as a piece of historical evidence in the quest for HD treatments.

It will also serve as a reminder of the dire need for truly effective approaches against a devastating disease that has reminded the world how the discovery of the first effective drug for any neurological disorder has continued to elude science.

To take, or not to take, unproven supplements in the fight against Huntington’s disease

Should people facing Huntington’s disease take creatine and other supplements to relieve or prevent symptoms?

I do.

I saw HD inexorably destroy my mother’s ability to walk, talk, and care for herself. She died eight years ago this month. I tested positive for HD in 1999 and since then have worried daily about when it will strike.

There is no treatment to slow HD’s devastation of the brain. So I’ve been open to taking supplements that might help.

In early 1996, just shortly after learning of my mother’s diagnosis, I started taking coenzyme Q-10 (Co-Q), a vitamin-like substance found throughout our bodies and seen by researchers as a possible way to help remedy the energy deficits suffered in HD.

In 2004, when Dr. LaVonne Goodman introduced a “treatment now” regimen and clinical trial of safe supplements that had shown promising results in animal testing, I jumped at the chance to participate. I was the only presymptomatic individual in the small, three-year study, run under the auspices of Dr. Goodman’s Huntington’s Disease Drug Works (HDDW).

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 Co-Q; two g of omega-3 oil; two g of blueberry extract; and ten g of medical-grade creatine. The trial paid for and delivered the supplements.

The trial did not show significant improvement for any of the symptomatic participants. “The only thing that appeared to be helpful was trehalose,” Dr. Goodman said in a February 9 phone interview. Today, almost a decade later, the supplements remain medically unproven to affect HD.

Nevertheless, scientists still think that trehalose, Co-Q, and creatine might still provide help in treating HD. Since the end of the HDDW, I have continued to take all of the supplements, spending about $2,000 per year. In fact, several years ago, relying on medical advice, I roughly doubled my daily intake of creatine to about 20 g.

I get semi-annual blood tests to monitor potential kidney damage, which creatine can cause. I also drink plenty of water throughout the day to prevent dehydration, which can occur at doses higher than 10 g. Creatine also can cause weight gain.

Am I wasting money and endangering my health?

I don’t think so. A few years ago, one of the doctors at the local Huntington’s disease clinic told me to stay on the supplements, observing that the combination of substances might be helping to delay my HD onset. I inherited the same degree of mutation as my mother, but, at 54, have passed the age of her onset.

The yin-yang of supplements

Whether others in the HD community should take creatine and other supplements is an individual choice ideally made in consultation with a doctor.

During our interview, the Seattle-based Dr. Goodman reviewed the pros and cons of taking creatine.

She cautioned against taking high doses of the substance, because more serious side effects occur at higher dosage, and urged people to consult a physician before starting any supplement.

She stressed that people need to understand the “yin-yang” involved in the decision to take supplements.

“Yes, you want to take care of yourself,” Dr. Goodman said. If they do nothing else, supplements can at least furnish a “very important” placebo effect and the prospect of hope, she said.

Dr. LaVonne Goodman (photo by Gene Veritas)

The placebo effect is a “real” phenomenon, she observed. “If you could bottle it, it would be great.”

However, taking supplements also reminds asymptomatic gene carriers of their risk, she added.

More importantly, people’s use of supplements could also obstruct the path to other, potentially far more promising treatments, she said.

The benefits of supplements “need to be counterbalanced with the need to test promising new drugs, or we will never have better treatments for Huntington’s,” she explained.

Interfering with clinical trials?

“There are so many competing interests here,” Dr. Goodman continued. “We all want to believe that (creatine) is helpful, because it’s available, and we can take it, so why not do it, we say. This is what I said with HDDW trials. Well, yes, but it needs to be measured. Otherwise, we’re going to know nothing more than we did.”

“It is important for people to know that if they take these things, they can’t be in clinical trials at the same time. We deplete our clinical trial participant base, which is going to impede progress for finding better treatments. There’s the yin-yang. And people need to hear both.”

However, Dr. Goodman noted that individuals could do both: to become eligible for a clinical trial, individuals could clear the supplements out of their system so that they don’t interfere with the measurement of the tested drug’s effects, then resume the supplements after completing the trial.

I would stop taking my supplements in order to qualify for a trial, although until the most recent creatine trial (see below), practically every trial has targeted only symptomatic individuals.

Dr. Goodman underscored the need to treat creatine and all other supplements as “medicines.” Supplements should meet USP (U.S. Pharmacopeial Convention) standards, she added. The HDDW website contains information on supplement safety. Further information on supplements is available at Huntington’s Disease Lighthouse Families.

(I buy my creatine from my local GNC outlet but plan to search for a better grade of the product.)

All drugs, including FDA-approved ones, produce side effects and can affect individuals differently, Dr. Goodman noted.

Regarding creatine, she concluded: “If it’s not watched closely, it may cause more harm than good.”

A historic trial

People in the HD community became excited about creatine as a potential treatment after Harvard University’s online news service on February 7 published an article titled “Nutritional supplement slows onset of Huntington’s.”

According to the article, a team of researchers based at the Harvard-affiliated Massachusetts General Hospital had finished a historic Phase II clinical trial that produced MRI scans showing evidence of the slowing of brain atrophy (shrinkage) in HD gene carriers who have yet to manifest the classic symptoms of the disorder. Sixty-four people took part.

Participants took up to 30 g of creatine per day.

According to Steven Hersch, M.D., Ph.D., the trial, called PRECREST (Creatine Safety and Tolerability in Premanifest HD), was a “huge step” for three reasons – including its impact on a separate creatine trial for symptomatic patients called CREST-E (Creatine Safety, Tolerability, and Efficacy in Huntington’s Disease)

“One, it’s the first therapeutic trial that has tried doing prevention,” Dr. Hersch, the study’s senior author and a long-time HD researcher, said in a February 11 phone interview. “Two, because we created a design that let anybody participate who’s at 50% risk, as well as those who have tested positive. And three, the imaging finding increases the probability that CREST-E will show a clinical benefit.”

Dr. Steven Hersch (photo from HDSA website)

Currently in progress and still recruiting participants, CREST-E is a phase III trial – the final step before drug approval (click here to learn how to enroll).

The PRECREST administrators recruited untested at-risk individuals who were then tested for the purposes of the trial as well as individuals who already knew that they have the HD mutation. However, those who entered the study untested did not receive their results, which were only known to the statistician. Thus, they avoided the potentially traumatic psychological aftermath and remained protected from genetic discrimination.

“The ethical challenges for those recruiting and conducting trials include how to accommodate nontested at-risk individuals while preserving a noncoercive choice regarding genetic testing,” states an editorial about PRECREST in the March 2014 issue of the prestigious journal Neurology, adding that “unequivocal changes” occur in the brain of presymptomatic individuals “15 to 20 years before conventional clinic-based diagnosis.” An article on PRECREST by Dr. Hersch, lead author Herminia D. Rosas, M.D., and nine other collaborators appears in the same issue.

For these and other reasons, 90 percent of at-risk individuals choose not to test, Dr. Hersch explained.

The MRI changes and other data from PRECREST will eventually be assessed in CREST-E, Dr. Hersch explained. CREST-E is also doing MRI imaging. With nearly 600 participants so far, it will be large enough to show whether the benefits shown in PRECREST images correspond to a significant slowing of HD.

Avoiding false hopes

As with many news articles about clinical trials and other scientific experiments, the Harvard report’s headline, which claimed the supplement slowed the onset of HD, inaccurately reflected the researchers’ results as reported in the actual scientific article.

“While slowed atrophy suggests that creatine could slow preclinical progression, the potential clinical impact of these findings on delaying the onset of HD is unknown and must be defined by an efficacy study designed to measure it,” the Neurology article states.

Nor can the public buy the high-quality creatine used in the study, as it’s prepared specially for clinical trials.

“I don’t want people to take from this study that they ought to go running out and take a bunch of creatine or take it at these doses,” said Dr. Hersch. “Even though the imaging benefit is very exciting, we don’t know what it means clinically. It doesn’t provide the evidence that would lead me to recommend that people take it. The high doses that we used should also not be used without medical supervision.”

As noted in the Neurology article, some PRECREST participants suffered stomach upset and diarrhea caused by the creatine. About a dozen people had to drop out of the study.

Regarding the study’s clinical significance, Dr. Goodman offered an assessment similar to that of Dr. Hersch.

The widely read HD research website HDBuzz.net also weighed in.

“How much hope and how my hype?” an HDBuzz article asked. While recognizing the importance of the study, it pointed out that the causes and effects of the slowed shrinkage in the brains of the PRECREST participants need further study.

“It’s possible that creatine causes HD brain cells to bulge or swell without making them healthier,” it states. “Swelling like that could produce false optimism and might even be harmful. That’s not something this trial can tell us either way, because the patients weren’t followed long enough to see whether creatine treatment delayed the onset of symptoms.”

“The participants in PRECREST who took creatine but did not have the HD mutation did not experience any brain swelling, so this is an unlikely explanation for our findings,” said Dr. Hersch. “Including and treating these subjects was very unusual. However, we did so to allow us to answer questions like this.”

Awaiting the Holy Grail

“HD researchers face a major challenge in finding a treatment for the pre-manifest,” I wrote in 2011. “It’s really the Holy Grail not only for HD, but also for other neurological diseases such as Alzheimer’s in which brain damage occurs many years before symptoms appear. Ideally, researchers want to design medications that will completely prevent these diseases.”

The Neurology editorial used the term “Holy Grail,” too, in noting how the PRESCREST study “investigates a potentially neuroprotective agent designed to delay disease onset.”

The word “potentially” is key.

As Dr. Hersch explained, the PRECREST findings about slower shrinkage “suggest” that creatine provides a benefit, but they don’t permit researchers to say anything about delayed onset of symptoms in presymptomatic individuals or a longer lifespan for patients.

It remains for the CREST-E Phase III trial to produce similar brain scan results – and an actual effect on symptoms.

“If CREST-E shows efficacy in slowing down the disease in people who are symptomatic, I would think that most people would think that you may be slowing down the disease in people who aren’t symptomatic yet as well,” he said.

Until treatments become available, presymptomatic gene carriers like me will continue to face the extremely difficult decision about whether to take supplements.

I’m grasping at creatine and other supplements in the hopes of delaying onset until researchers succeed. 

‘Drug hunters’ bring hope to Huntington’s families

Scientists and pharmaceutical companies are making steady progress in the search for treatments for Huntington’s disease, increasing the hope that this generation of HD-affected families will finally get long-awaited relief from its devastating, ultimately deadly symptoms.

This was the message of the Sixth Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc., from February 7-10, 2011, at the Parker Palm Springs hotel in Palm Springs, California.

After delivering the keynote address to about 250 prominent scientists, physicians, pharmaceutical representatives, and supporters of the HD cause on the evening of February 7, I spent the next three days observing scientists speak on the latest advances in HD research and their plans for finding treatments.

This was a conference of “drug hunters,” the people in the trenches of university, corporate, government, and foundation labs who are working as quickly as possible to develop a myriad of ways to stop HD.

Informally known as the “cure Huntington’s disease initiative,” CHDI invited researchers to outline progress in four main areas, which I describe below after the following overview interview with Robert Pacifici, Ph.D., CHDI’s chief scientific officer.

Overview video and summaries

Click “play” on the video below to see my interview with Dr. Pacifici. In addition to outlining the main points of the conference, Dr. Pacifici urged the HD community to participate in trials that will assist scientists in their quest for treatments.

You can also read a daily summary of the conference at the excellent new science website http://www.hdbuzz.net/.

Gene Veritas interviews CHDI chief researcher Robert Pacifici from Gene Veritas on Vimeo.

Area 1: Decreasing huntingtin

The first and most promising area involves the attempt to attack HD at its genetic roots. This approach is called “lowering huntingtin,” the protein produced in our cells by the huntingtin gene. HD people have a mutated gene, and that mutation produces a faulty huntingtin protein, which compromises the health of brain cells.

As a result, they have two kinds of this protein. There is the “good,” or normal, huntingtin, which is produced by the gene inherited from the non-HD parent. And there is “bad,” or abnormal or defective huntingtin, which is produced by the gene from the parent with HD.

“In my six years at CHDI, we’ve seen (potential drug) targets come and go,” said Douglas Macdonald, Ph.D., CHDI’s director of drug discovery. “Only one has continued: huntingtin.”

Above, Dr. Macdonald addresses the conference. Below, a slide from his presentation pointing out the need to lower huntingtin before symptoms begin (photos by Gene Veritas).

CHDI’s current budget stands at approximately $100 million, a substantial sum compared to the amounts available just a decade ago in the world of HD research. CHDI intends to spend about half of the drug development portion of its budget in the area of huntingtin lowering. This approach appears to come closest to the idea of a “cure,” although most scientists believe that HD will be merely controlled like diabetes or high cholesterol, and then only with a cocktail of drugs.

On this front CHDI has partnered with a number of firms and labs: Isis Pharmaceuticals, Inc. (click here to read more); Alnylam Pharmaceuticals; Evotec; Dr. Neil Aronin of the University of Massachusetts School of Medicine; Dr. Paul Patterson of the California Institute of Technology; Dr. Edvard Smith of the Karolinska Institutet in Stockholm, Sweden; and Dr. Robert M. Friedlander of the University of Pittsburgh School of Medicine. Novartis, one of the world’s largest pharmaceutical companies, is also engaged in this area of research.

Both Isis and Alnylam are very close to applying for permission from the Food and Drug Administration to begin human clinical trials with their potential drugs.

Challenges

While potentially very effective for those with HD, lowering huntingtin also poses several huge challenges for scientists, Dr. Macdonald pointed out.

What should be targeted, good or bad huntingtin or both? How much should the protein be lowered? What part of the brain should be treated? And at what stage of the disease should a drug be given to a patient or non-symptomatic, gene-positive individual such as myself?

After all, the huntingtin protein is needed for the development of the cell. Even defective huntingtin does some good, Dr. Macdonald explained.

Unfortunately, so far the potential drugs for lowering huntingtin do not distinguish between the good and the bad, so reducing the bad decreases the good by the same percentage. (I’ll be writing soon on how Isis is attempting to find a way to keep the good while lowering the bad.)

In an interview, world-renowned HD specialist Dr. Michael Hayden, of the University of British Columbia, told me that beyond decreasing the defective huntingtin, another solution would be to increase the supply of the good.

Huntingtin’s job

For a long time, scientists had no idea about the function of huntingtin. In the last few years, however, they have made a number of discoveries.

Huntingtin is like the spider at the middle of a web of cellular functions, explained Scott Zeitlin, Ph.D., of the University of Virginia School of Medicine. If you reduce its capabilities, you reduce the strands in the web, in other words, the things the cell can do. And if you remove it, you sever the strands, that is, you completely turn off important processes.

Dr. Scott Zeitlin explains the functions of the huntingtin protein (photo by Gene Veritas).

In his presentation, Dr. Zeitlin identified six major functions for huntingtin, including the transport of materials inside the cell, the decoding of genes, and regulating metabolism. On the whole, huntingtin helps keep the cell stable (protein homeostasis).

It also helps keep the brain as a whole stable.

Dr. Zeitlin also pointed out that huntingtin is important in the development of an embryo. Too little huntingtin in a mouse embryo, for example, causes the animal to be born deformed.

Other views on lowering huntingtin

Providing the example of protein regulation in another disease, Dr. Karen Chen of the Spinal Muscular Atrophy (SMA) Foundation demonstrated how an Isis compound has improved the health of mice afflicted with SMA. Adjusting huntingtin could work similarly in HD, she suggested.

In his presentation, Dr. Andreas Weiss of the Novartis Institute for Biomedical Research discussed the methods and technologies used to track the presence of normal and abnormal huntingtin in cells and brains. Data from these observations will help in the design and dosing of treatments – including, once again, the question of how much to lower huntingtin.

(For an informed outlook on lowering huntingtin and controlling HD, watch my interview with Dr. Hayden in the video below. Dr. Hayden’s lab collaborates with Isis on attempts to lower huntingtin. In this interview Dr. Hayden also recounts his journey from working as a young doctor in South Africa to conducting research in North America, and he discusses the increased number of HD patients and the deep discrimination faced by HD-affected families everywhere. For additional background on Dr. Hayden, read this article.)



Gene Veritas interviews Huntington's disease expert Michael Hayden from Gene Veritas on Vimeo.


Area 2: saving brain cells

The second main area for researchers involves the problem of dysfunctional brain cells and how to save them early enough to prevent the disease from advancing.

This portion of the conference focused on such key problems as synaptic dysfunction, the misfiring the synapses, where the signals between brain cells are carried. The deficit in brain cell activity was also examined. Researchers also addressed the problem of “excitatory cell death”, in which dying cells release chemicals that, in turn, overstimulate and cause damage to other cells.

Dr. Michael Orth of the University of Ulm, Germany, discussed transcranial magnetic stimulation (sending of weak electrical currents into the brain), a method he has used to measure brain activity in pre-symptomatic, gene-positive individuals like me. He observed abnormal activity in the motor cortex portion of the brain, the area responsible for movement. Chorea, or the shaking and trembling of the body, is one of the primary symptoms of HD.

Dr. Vahri Beaumont of CHDI outlined the organization’s programs for combating synaptic dysfunction, which is primarily the problem of miscommunication between neurons. She noted that such dysfunction can occur as early as two decades before a person has noticeable symptoms. A couple of compounds currently used in clinical trials for other diseases could be beneficial for HD patients, she suggested.

Along these lines, Dr. Pacifici noted that large pharmaceutical companies have shown great interest in this area of brain health and have developed many compounds. These compounds can be “repurposed” quickly and moved into HD trials in the near future.

Area 3: bioenergetics and HD

The third group of presentations focused on a well-known problem caused by HD: an individual’s extremely high usage of energy, which causes patients to lose weight. Scientists are examining the causes of this problem at the cellular level and seeking remedies.

This characteristic of HD has led patients and asymptomatic gene-positive individuals to take supplements such as coenzyme Q-10, creatine, and trehalose. These might increase cellular energy. These substances are under study by HD researchers.

This session of the conference included discussion of dysfunction in the mitochondria, the powerhouses of the cell, and possible drug targets.

Dr. Pacifici that scientists are seeking to understand the specific causes of the energy deficit in HD and match them up with possible drug molecules.

Area 4: fertilizers for the brain

The final portion of the conference focused on “neurotrophic factors” (growth factors), which help maintain brain cells and the brain’s functions.

In Dr. Pacifici’s words, neurotrophic factors are like “fertilizers” for the brain. With HD, there is a shortage of certain molecules – the fertilizer – which must be put back into the brain to make it grow new cells and stay healthy.

Dr. João Siffert of Ceregene described his company’s implementation of a Phase II human clinical trial for CERE-120, a drug that is intended to increase the growth factor neurturin in the brains of Parkinson’s disease patients. Ceregene is conducting pre-clinical research on CERE-120 for use in HD.

The protein BDNF

One of the most frequently mentioned growth factors in HD research is BDNF, a protein known as brain-derived neurotrophic factor. As stated by Dr. Jordi Alberch of the University of Barcelona, BDNF is a potent protector of neurons in the striatum, one of the areas of the brain most affected in HD. The level of BDNF decreases in HD patients.

In his presentation on brain receptors that link up with BDNF, Dr. Moses Chao of the New York University School of Medicine noted that the lack of the substance is a cause of the neuropsychiatric symptoms of HD (such as depression).

Dr. Moses Chao speaks on BDNF (photo by Gene Veritas).

BDNF, he observed, contributes to a number of important activities in the brain, including the development of the cytoskeleton (the skeleton of the cell) and the ability of the synapses to adjust their strength. BDNF also helps cells survive.

As Dr. Chao pointed out, scientists first thought it might be possible to inject BDNF directly into the brain to help patients. However, in their experiments they encountered difficulties in delivering the BDNF, and it proved to be very “sticky,” meaning that it did not move easily in the brain. There were also negative side effects.

More recently, Dr. Chao explained, scientists have sought ways to bypass these problems. That research has focused on the BDNF receptors, molecules in the brain that link to BDNF so that it can carry out its tasks. Scientists are also examining substances that can bind to the receptors and act as a substitute for BDNF.

Evidence has also shown for quite some time that certain chronic antidepressants increase BDNF levels.

Scientists have long known that exercise stimulates the production of BDNF. Therefore, Dr. Allan Tobin of CHDI has conducted a workshop to investigate the use of molecules that could mimic the effect of exercise on the brain and therefore increase BDNF levels.

In his presentation, Dr. Alex Kiselyov of CHDI reviewed several “paths” that might be followed in solving the BDNF deficit problem.

Visiting the poster session

As with most scientific conferences, the CHDI event included an area where scientists could present posters summarizing their research.

The collection of posters was like an ultra-advanced science fair. Authors gave short oral presentations to other scientists circulating through the area, and a panel of three judges chose the three top posters. After hearing formal presentations, the conference participants selected a winner.

(In the video below you can watch the scientists as they examine and discuss the posters.)



Huntington's disease drug hunters view posters at 2011 research conference from Gene Veritas on Vimeo.

This year’s winner was a poster by Dr. Ray Truant of McMaster University in Hamilton, Ontario, and his graduate students Nicholas Caron and Randy Atwal. It was titled “Measuring Flourescence Lifetime in Living Cells Reveals Huntingtin Exon1 Structure at Nanometer Resolution.” It was subtitled “N17 ‘Loop-back’ Model is Affected by Phosphorylation and Polyglutamine Expansion.”

As explained to me by Caron, the experiment involved the use of an extremely powerful laser microscope to examine the real time workings of live mouse cells. They observed actual protein-to-protein interactions.

The normal huntingtin protein has a kind of hinge, but the abnormal protein becomes too long and too rigid and thus makes this hinge less flexible.

The team concluded that they can use this technique to screen for small molecules that can influence the disease process within the cells. The goal is to find ways to reduce toxicity within cells.

Their research builds on the 2009 discovery of a “molecular switch” that might be used to stop part of the disease process in Huntington’s.

Ph.D. student Nick Caron (above) with the winning poster, and Dr. Ray Truant (below) explaining the team's project to the conference participants (photos by Gene Veritas).

Another piece of the puzzle

The featured speaker of the conference was the eminent neuroscientist Dr. Solomon H. Snyder of the University of Johns Hopkins Medical School.

Dr. Snyder provided a look back at the last five decades of discoveries about the brain, its receptors, and the many important kinds of drugs resulting from this research.

In 2009, he and other scientists in his lab reported a key new finding about HD involving a protein called Rhes. Located only in the striatum, Rhes binds to the huntingtin protein. When it binds with abnormal huntingtin, it causes cell death.

As Dr. Synder stated, the limited presence of Rhes in the striatum could help explain why that area of the brain suffers more damage than others.

Researchers are now looking for ways to stop the harmful effects of Rhes. Dr. Snyder stated that a Rhes drug might be safe, because its use would be required only in the brain, not all over the body.

CHDI’s key role

In the final session of the conference, Dr. Pacifici and two lead CHDI researchers summarized CHDI’s work in developing completely new compounds that might be able to treat other problems that occur in HD-afflicted brains. Dr. Ignacio Muñoz-Sanjuan, the vice president for biology, and Dr. Celia Dominguez, the vice president for chemistry, detailed the efforts to prepare two of these compounds for testing in animals.

(Watch the video below for a part of Dr. Muñoz-Sanjuan’s talk and to get a view of the scientists at work in the main conference room.)

Drug hunters at work at 2011 Huntington's disease meeting from Gene Veritas on Vimeo.

The development of these and other CHDI compounds reveals how the organization has assumed an ever more important leadership role in the search for treatments and a cure. As a virtual biotech company, CHDI not only contracts with other firms and labs to carry out research and testing, but pioneers in new areas. CHDI is determined to explore as many remedies as possible.

At this conference CHDI’s importance was further reflected by the record number of attendees and posters. In fact, this year the organizers needed to add a couple of extra rows of seats to accommodate attendees.

“At any time, CHDI is working full-speed on about ten different drug development projects,” noted Dr. Jeff Carroll (click here to read more), an HD researcher and, like me, gene-positive for the disease. “For a sense of scale, that’s more programs than most large pharmaceutical companies have in all areas of brain research, including much more common diseases like Alzheimer’s or Parkinson’s disease. CHDI is changing the pace and scope of HD drug development.”

Reasons for optimism

Dr. Pacifici concluded that HD families can “have hope.”

“There are an incredible number of shots on goal,” he said. “We’re doing this as quickly and as rationally as possible, and I think that there’s really good reason to be optimistic that within the next period of time we’re going to start seeing the creation of new chemical entities, new drugs that were specifically designed with Huntington’s in mind.”

“I can see that we’re getting to the final stretch. It’s been a long marathon,” said Dr. Hayden. “And I’m optimistic. I’ve been in this field for 34 years. We did the first predictive test 25 years ago in Vancouver in 1986. So we’ve watched the whole development.

“So for me the opportunity to work with many of these companies, keep them focused on the issues, and help to provide the reagents and resources to get this done is just an incredible privilege and an exciting time.

“We know that for families listening to this, every day counts.”

The best Christmas gift of all

This week I received the best Christmas gift of all: a clean bill of health during my annual visit to the local Huntington’s disease clinic.

I tested positive for the HD gene in 1999, and my mother died of the disease in early 2006 at the age of 68. I don’t know exactly when her symptoms began, but, as I look back, it seems that classic early signs such as mood swings and depression began in her late 40s.

I turn 51 on December 31, and I’m getting closer to the point at which my mother started having chorea, or the trembling of the limbs, one of the major symptoms of Huntington’s.

In order to monitor my health and strategize on ways to avoid onset of the disease, each year I undergo an examination at the Huntington’s Disease Society of America’s Center of Excellence for Family Services and Research at the University of California, San Diego. On December 14, I went through an intensive, two-hour battery of cognitive testing at the center. This past Tuesday, December 21, I was examined by one of the center’s physicians.

He found no evidence of chorea, and he informed me that my 2010 cognitive results matched the 2009 tests.

So I remain stable!

Bonus time

I felt enormously relieved.

The visits are extremely stressful, because there are no treatments for the root causes of HD. Symptoms eventually appear in all gene-positive individuals.

Onset would mean that I would begin a steady decline towards death. My mother’s symptoms got steadily worse. During the 15 years (or more) of the disease, she lost the ability to walk, talk, think, and swallow. She was only a faint shadow of herself when she died in a nursing home.

So I realized once again that every extra moment of good health is a bonus.

A winning team

The doctor recommended that I maintain my routine.

Since 2004 I have taken the main supplements recommended by the Huntington’s Disease Drug Works (HDDW) program: trehalose, creatine, coenzyme Q-10, omega-3 fish oil pills, and blueberry concentrate pills. Although there is some evidence suggesting these substances could affect HD, at this point there’s no way to prove that they have actually helped me.

But, the doctor said, they might be helping me to remain stable.

HDDW used to cover the cost of the supplements but is no longer doing so. I will have to shell out two or three thousand dollars annually to pay for them. Because they’re not officially approved remedies, insurance won’t cover them.

Nevertheless, the doctor said the cost is justified.

I agree. There’s a saying I learned in following Brazilian soccer: you don’t mess with a winning team.

In my case, the team includes far more than the supplements: pills to avoid depression and anxiety, psychotherapy, exercise, dedication to my family, the nurturing of my faith and spirituality, and sharing my journey as an HD-positive person through this blog.

The need for hope

In writing this, I must admit that part of me feels enormously guilty.

So many others in the HD community already experience terrible symptoms. Young, at-risk people struggle with the news of their parents’ diagnoses and decisions about genetic testing, and newly tested individuals who are gene-positive suddenly fear a dark future.

Will my desire to celebrate a symptom-free Christmas and New Year’s Eve make others in the community feel even more frustrated with their helpless predicaments?

Probably not. People in our community are generally very understanding and sympathetic with a whole range of situations. But I feel so badly for others – and want even more badly for a cure to come soon.

We in the HD community we all need hope – especially at this time of year.

I may never know why in the year 2010 I did not have symptoms. In 2011 they very well could start.

But my lack of symptoms could very well serve as a piece of evidence in the mystery of HD and the search for treatments and a cure. That, after all, is a big reason why the results of my cognitive testing go to the researchers.

And I want to help others.

A gift of health and time

On the brighter side, my current state of stable health will permit me to continue the fight for greater awareness about Huntington’s disease and the quest to end it.

As I noted in my previous entry, on February 7, 2011, I will represent the HD community as I give the keynote speech before scores of scientists at the “Super Bowl” of Huntington’s research.

More than ever before, I’ll be putting myself in the public eye and calling fervently for a cure.

Thanks to this year’s best Christmas present of all, I can carry out that mission with a strong and clear voice.