Friday, December 24, 2010
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!
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.
Thursday, December 16, 2010
I will humbly but purposefully attempt to meet this challenge when I give the keynote speech to Huntington’s disease researchers from around the world at CHDI’s 6th Annual HD Therapeutics Conference at the Parker Palm Springs hotel in Palm Springs, CA, on February 7, 2011.
I recently received the formal invitation to speak from Robi Blumenstein, the president of CHDI Management, Inc., which implements the goals of the CHDI Foundation, Inc., informally known as the “cure Huntington’s disease initiative.” Funded by an anonymous donor who has put tens of millions of dollars into the project, CHDI functions as a virtual biotech company and is the leading private source of HD research funds.
The conference will begin with my speech on the night of February 7. Taking place one day after professional football’s Super Sunday, the four-day CHDI conference serves as the “Super Bowl” of Huntington’s research.
At last year’s 5th annual conference, which I attended (click here to read more), several hundred scientists participated. Dozens gave presentations regarding the latest breakthroughs in understanding HD and finding drugs to stop it. Representatives of the Huntington’s Disease Society of America (HDSA) and the HD associations of other countries, as well as individuals from affected families and pharmaceutical companies, participated in the meeting. Another turnout of several hundred is expected for 2011.
An energizing task
Robi first mentioned the possibility of me as a keynoter during the 2010 conference. Robi, a regular reader of this blog, and I had met in July 2009, when I spent a day at CHDI’s research headquarters in Los Angeles (click here to read more). Since then, we have periodically exchanged ideas about the HD cause.
The idea of taking on such an important task energized much of my Huntington’s disease advocacy this year. I have been thinking intensely about the speech ever since. I’ve written most of this year’s blog entries with an eye to garnering ideas for the keynote.
It’s a huge responsibility, because, for 60 minutes, I will be representing the HD community. It’s now abundantly clear that HD-affected families and the scientists are inextricably linked. The families need the scientists to stop HD, and the scientists need the families to confirm their research through clinical and observational trials.
Just this past Tuesday, December 14, I did my annual battery of cognitive testing at the HDSA Center of Excellence for Family Services and Research at the University of California, San Diego. For two hours, under the guidance of a volunteer pre-med student, I performed such exercises as repeating series of numbers forward and backwards, creating lists of words beginning with a particular letter, and discerning patterns of diagrams.
These tests help measure whether symptoms such as dementia have begun, and they provide raw data to researchers studying brain imaging and other aspects of HD.
Finding a new dimension
In my speech, I will need to illustrate the many common challenges faced by HD families. This year I’ve become especially attuned to the suffering of affected and gene-positive individuals by spending many hours reading the stories they have posted through Facebook HD groups such as “Ri Hdsa” and “hd family.”
As I write my speech, I’ve followed the fate of a child hospitalized with severe juvenile HD and read the messages of a young, affected woman fearful that she’ll never be loved and be able to have children. There are many other stories like these.
I also must prepare a speech that brings the human side of the disease home to the researchers who are accustomed to focusing on their lab work. Building on past keynote speakers such as the HD-positive former NBC correspondent Charles Sabine, I must discover a new dimension of the presymptomatic HD person and provide the scientists with some new insight into the disease and their goal of eliminating it.
Exiting the HD closet
At the keynote, I will take my biggest step ever out of the HD closet. I long remained in that closet for fear of discrimination at work, on insurance questions, and in the health care system.
As I did in Brazil in June and at Vertex Pharmaceuticals in September, I will speak in public using my real name. The first two speeches didn’t receive any outside publicity beyond my blog, but my CHDI presentation will be seen by people from around the world and likely generate comments on the web. I am also mulling whether to post a video of the keynote on the web.
I made the 2010 talks and other forms of more public advocacy a trial run for the CHDI talk and the likely greater impact it will have. In the coming days I also will consult trusted friends and professional colleagues on the question of exactly how to become more public and how to deal with the effects, both positive and negative.
So far, speaking out publicly has helped make more people aware of HD, but it has also caused me stress as I worry about long-term, as yet unforeseeable consequences on my family, my job, and my psyche.
A pivotal moment
At this moment, three important points in my life are converging: the end of an extremely busy and productive year on the HD front (for me personally and for the cause as a whole); the holidays and my 51st birthday on December 31; and my preparation to kick off the CHDI Super Bowl.
The holidays will be especially poignant because this December 26 marks the 15th anniversary of the day I received the news of my mother’s diagnosis. February 13 – one week after the CHDI meeting – will mark the fifth anniversary of my mother’s death.
The CHDI keynote will be a pivotal moment. In many respects it marks the culmination of those 15 years of my personal battle to avoid Huntington’s disease and to build support for the cure.
My life’s mission
This speech symbolizes my life’s mission: a personal struggle against a cruel and fatal disease that cut short my mother’s life at age 68 and likely will similarly inflict itself on me – and, somehow, a joining of hands with the researchers pioneering the newest frontiers of science in order to unlock the mysteries of Huntington’s and by extension other brain diseases.
The aftermath will open a new phase in my life as I seek to become a more effective advocate. This will involve the big effects of becoming ever more open about my HD-positive status, but also the small effects of action in one-on-one conversations, in venues such as the local HD support group, and in writing about the scientific work that I fervently hope could save me and thousands more from the ravages of Huntington’s.
Wednesday, December 08, 2010
Vertex Pharmaceuticals is a prime example of this trend, which includes such firms as Isis Pharmaceuticals, Inc., and Alnylam Pharmaceuticals.
In mid-2008 the San Diego unit of Vertex began a project to find ways to block the actions of mutant huntingtin protein, which causes the death of brain cells.
Today two small teams of scientists devote themselves full-time to the HD project at this important drug discovery firm. Although they stressed that the project is still very much in the early stages, Vertex scientists spoke enthusiastically about their plans to decipher and attack the disease.
Looking for a pill
The project originated with a collaboration with CHDI Foundation, Inc., the “cure Huntington’s disease initiative” backed by an anonymous donor, but Vertex has branched off on its own and has continued Huntington’s research with internal funding.
“We’re very early (in the research),” said Paul Negulescu, Ph.D., Vertex vice president for research and the site head of the San Diego facility. “But we do believe that it may be possible to influence the course of this disease with small-molecule therapies in the years ahead.”
By “small molecules” Dr. Negulescu means that Vertex aims to produce a pill or series of pills that HD people and gene-positive individuals could take to control the effects of mutant huntingtin. Pills represent a far less invasive method of treatment in comparison with others such as an injection, the insertion of a catheter into the brain or the spinal cord, or an operation.
Lessons from cystic fibrosis
Vertex hopes to extend its research on two promising drug candidates for cystic fibrosis (CF) into the Huntington’s field.
Like HD, CF is a genetically caused condition in which proteins malfunction. The potential drugs help a key protein in CF do its job of keeping the airways of the lungs moist and therefore capable of fighting off dangerous bacterial infections, the most devastating, and ultimately deadly, symptom of CF.
One of those candidates, VX-770, is already in Phase III clinical trials. Vertex will review the data from the trial in the first half of 2011. If successful, the company will then seek approval from the federal Food and Drug Administration (FDA) to market the drug, which would be taken as a pill.
The community approach
Vertex collaborated closely with the Cystic Fibrosis Foundation and the CF community to develop VX-770 and its other candidate, VX-809.
“We’re going to apply the best science that we can and learn the lessons that we can from the CF program, not only scientifically but in terms of how to work with a disease community that is focused on a single disease,” Dr. Negulescu said of the HD project.
“There are many things that a community brings to a research effort – not only patients and their passion about their disease and helping us understand what’s really important to them, but also to basic research, and, in some cases, like with CHDI and our early efforts with them, access to funding. All of that comes together to create a better chance for success, to make progress on the disease. That’s our model. That’s how we want to go after it, as a community, as a network.”
As part of this community approach, Vertex invited me to present my story about living gene-positive for HD. On September 24 I gave a talk before 50 Vertex employees. It was titled “Gene-positive for hell: my family’s struggle against Huntington’s disease." (Click here to read more.)
On October 22 Dr. Negulescu and nine other Vertex scientists attended the tenth annual Celebration of Hope Gala of the San Diego chapter of the Huntington’s Disease Society of America. It was the largest contingent of scientists from a single company in the history of the fundraising event. (Click here for my account of the gala.)
Going after ‘smaller diseases’
Vertex also focuses on drugs for the alleviation of viral diseases, pain, cancer, autoimmune disorders, epilepsy, and inflammation.
Recently Vertex’s completed three large Phase 3 trials of one of these drug candidates, telaprevir, in people with hepatitis C. Based on the Phase 3 results, Vertex recently applied for approval of telaprevir from the FDA. (Click here to read a news report on telaprevir.)
“One of the hallmarks of Vertex is that we’re willing to go after the smaller diseases,” said Beth Hoffman, Ph.D., the Vertex vice president of biology and the coordinator of the HD program. "We also are willing to dig into the biology of the disease in order to make better drug candidates.”
Dr. Hoffman (photo by Gene Veritas)
HD has become important for Vertex “because scientifically there’s a good basis of understanding for what causes this disease, the genetics,” Dr. Negulescu said. “We’re taking this seriously as a disease and as an early-stage research program.”
As in CF and many other diseases, scientists believe that malformed, or “misfolded,” proteins are the culprit in Huntington’s.
Vertex researchers are trying to observe whether misfolding occurs in HD and to what extent.
They are also looking for ways to reduce the amount of the huntingtin protein in cells. They have already made some progress on this front, but they must also find a way for a drug to differentiate between normal and mutant huntingtin. Ideally, the drug would reduce the effects of mutant huntingtin while leaving normal huntingtin alone or only minimally affected.
Huntingtin exists throughout the body and is essential for life, although scientists have yet to understand exactly what it does. Part of Vertex’s work is to help unveil that mystery.
“The CF program gave us confidence that a small molecule can affect the fate of the genetically impaired protein, to have it do what it’s supposed to do,” said Dr. Negulescu. “It might be possible to do the same thing with the huntingtin protein.”
On the cutting edge
One of the San Diego unit’s greatest strengths is its expertise in high-throughput screening (HTS), the automated, rapid testing of compounds. HTS allows the researchers to test the effect of hundreds of thousands of compounds on brain cells placed in tiny wells. The CF researchers used HTS to discover VX-770 and VX-809.
Dr. Hoffman demonstrates the preparation of a plate for use in the high-throughput machine at her left as HD team leaders Dr. Branka Mitrovic and Dr. Mike Liu look on (photo by Gene Veritas).
Dr. Negulescu described HTS as “sort of like panning for gold,” but at a very high speed.
“What we’re doing is really on the cutting edge of what’s out there in the HD field,” Dr. Liu said.
The San Diego unit stood among the early pioneers of HTS when it was known as Aurora Biosciences in the 1990s. In 2000 the Hereditary Disease Foundation of Los Angeles, which also focuses on HD, contracted with Aurora to do one of the very first high-throughput screenings of compounds for potential treatments in HD (click here to read more). Vertex, which is based in Cambridge, Massachusetts, acquired Aurora in 2001. Vertex was founded in 1989.
Helping brain cells
Another facet of the HD project involves neurogenesis: the repair of damaged brain cells or the replacement of dead ones with new ones. This research is at an earlier stage than the work on proteins. One approach might involve the stimulation of neural progenitor cells to become brain cells and connect to other brain cells, said Dr. Hoffman.
Dr. Branka Mitrovic leads the second Vertex team, which is examining ways to stimulate the production of growth factors, vital substances for the creation and nourishment of the brain. HD patients suffer from a shortage of such factors.
In the effort to stop the negative impact of mutant huntingtin, Vertex hopes to find a drug or drugs that will “stop disease before it progresses too far,” Dr. Negulescu said. Such remedies might also prevent asymptomatic gene-positive individuals like me from developing the disease or at least arrest it in its early stages.
Friday, December 03, 2010
Starting in July 2011, registries of HD patients, at-risk individuals, and family members from different parts of the world will be combined into a single database.
Called “Enroll-HD,” this new effort aims to make it easier for scientists to understand HD, identify potential participants in crucial clinical trials, and therefore speed the process of finding therapies and a cure.
The Enroll-HD sponsor, the CHDI Foundation, Inc., released information on the new program on November 19. Backed by an anonymous donor who has contributed tens of millions of dollars, CHDI is informally known as the “cure Huntington’s disease initiative.” CHDI collaborates with hundreds of scientists from around the world.
Enroll-HD will combine the existing REGISTRY and COHORT databases.
REGISTRY, a Europe-wide study, is run by the Euro-HD Network. Administered by the Huntington’s Study Group, COHORT stands for “Cooperative Huntington’s Observational Research Trial.” It operates in North America and Australia.
Both databases collect information about the genetic status, lifestyle, medical history, and disease progression of patients and gene-positive individuals.
Enroll-HD also will include participants from the newly founded Latin American network of HD-affected families, physicians, and researchers, the Red Latinoamericana de Huntington. Enroll-HD also will obtain information from countries such as Singapore, South Africa, and South Korea.
“It’s a natural progression to combine the successful HD observational clinical studies into one worldwide effort that will harness the power of greater numbers of research participants,” said Dr. G. Bernhard Landwehrmeyer, a professor at the University of Ulm, Germany, the chair of Euro-HD, and the principal researcher for Enroll-HD.
People already participating in REGISTRY and COHORT will continue to consult with the same physicians at regular appointment times.
To learn more about Enroll-HD, please click here.
Latin America’s contribution
One of the most striking aspects of Enroll-HD is the inclusion of Latin America, our neighbors to the south.
Venezuela in particular has played an important part in Huntington’s research. Dr. Nancy Wexler of the Hereditary Disease Foundation spent two decades researching the world’s largest extended HD family, located in the Lake Maracaibo region. Dr. Wexler developed the pedigree (traced the genetic history) of more than 18,000 individuals and collected more than 4,000 blood samples. This pioneering work helped lead to the discovery of the HD gene in 1993. (To learn more, see her sister Alice Wexler’s book Mapping Fate.)
About 580 million people live in Latin America – nearly twice the population of the United States. In rough terms, this means that some 60,000 people in the region could have Huntington’s. Studying these individuals and their families will provide a greater understanding of HD’s devastating effects and its terrible social impact.
It could also benefit HD families victimized by ignorance and poverty. Although conditions have improved for many in recent decades, most Latin Americans are still poor by our standards, and many have little or no access to quality education. In his visits to Colombia, HD activist Phil Hardt observed HD patients living in deplorable conditions – some even in old jail cells.
The Red Latinoamericana de Huntington can help raise awareness about HD throughout the region and perhaps stimulate government support for care programs and research. It also will tie the HD families and researchers from Latin America’s countries more tightly together – and also into the global network of researchers and care and advocacy programs.
More and faster research
Above all, by including Latin America’s HD families on the rolls of potential participants in clinical trials, Enroll-HD will vastly expand the possibilities of testing more drug candidates and carrying out faster research.
The Huntington’s research community faces an extremely difficult problem. As an orphan disease, there may not be enough subjects for trials as potential drugs become ready for testing. This problem is compounded by the fact that researchers have now identified more than 700 potential drug targets. Most trials minimally require dozens of participants, and others utilize hundreds and sometimes thousands of subjects.
In Europe, HD-affected and gene-positive individuals volunteer in sufficient numbers. Ironically, Americans do not. Despite this country’s power and overall wealth, denial, fear, and ignorance still dominate many families affected by HD. This lack of American participation makes Enroll-HD even more important.
Some might be concerned that Enroll-HD could become an attempt by scientists from rich countries to use people from poor nations as guinea pigs – that is, subjects tested unethically.
Fear of this kind of unequal relationship definitely exists in Latin America. I have frequently heard such concerns during my own historical research and travel in the region over the past quarter century.
But it’s unlikely that Enroll-HD will proceed with any kind of negative or arrogant attitude. All Enroll-HD participants will be protected by the strict protocols that govern research on human subjects.
The official Enroll-HD press release reassured current and future participants that “your samples will continue to be safely stored in the same biorepositories where they are now kept and all information about you will be securely stored in accordance with applicable local laws and regulations regarding the protection of your privacy.”
In addition, CHDI, European researchers, and Latin American representatives held on-the-ground preparatory meetings in Rio de Janeiro, Brazil, in February and Buenos Aires, Argentina, in June. The Rio meeting included representatives from Brazil, Argentina, Chile, Cuba, and Venezuela. Colombian and Peruvian representatives likely will participate in the future.
Reactions to the project
“I went to Rio because I wanted to extend a message of Hope to those in Latin America,” Dr. Ignacio Muñoz-Sanjuan, an HD researcher and the CHDI representative at the Rio meeting, wrote in his HD science blog. “This is not an American or European enterprise. It's a global fight to find a cure, which should be made available to all, rich or poor, in N[ew] Y[ork] or Maracaibo. But I also went there because we need more people to work with us. I need every affected person to participate: by donating blood, by speaking out, by enrolling in observational studies, in clinical studies. We simply cannot do it without the patients and the people at risk.”
Taíse Cadore, the vice-president of the Associação Brasileira de Huntington (Brazilian Huntington’s Association), wrote in a report that her organization “left the meeting with a great sense of optimism. We recognize the importance of our role in the development of this project and hope to be counting on the participation of our families.”
“The Red Latinoamericana de Huntington is very excited to become a part of the global Enroll-HD initiative and collaborate in this way with the international HD research community to better understand and treat Huntington’s disease,” Rodrigo Osorio, a native of Chile and the president of the Latin American organization, said of the official launching of Enroll-HD.
Bernhard Landwehrmeyer (right) converses with Rodrigo Osorio at the CHDI research symposium in Palm Springs, CA, in February (photo by Gene Veritas).
Inspiring global involvement
As a Latin America scholar and an HD-positive person who lost a mother to Huntington’s disease in 2006, I felt especially heartened with Enroll-HD’s recognition of the global character of disease and the need to include people of all continents in the search for treatments and in the resultant benefits.
I was especially happy to see my friends at the Brazilian Huntington’s Association receive the attention they deserve as potential contributors to the fight against HD. Without wealthy benefactors or government support, they have fought long and hard to build their organization solely on the grit and donations of HD-affected families.
Their efforts should inspire HD families in America to come out of the woodwork and redouble our efforts to strengthen our own community, educate the public about HD, and prepare for participation in clinical trials. (I will write more on the Brazilian association in my next entry.)
Ultimately, Enroll-HD can help build global awareness about the need to cure Huntington’s and other neurological disorders. We all share a common condition and, as we now understand, only together will we defeat HD and these other maladies.