The roots of our stigma

Huntington’s disease carries a huge stigma. Many families with HD cover it up, and many face discrimination. Surrounded by fear and ignorance, in many ways Huntington’s is stuck in the Dark Ages.

Why is this so?

Most people have not heard of Huntington’s or have only a very vague idea about it. It’s a devastating disease that people, once they see it, would rather not think about because it makes them confront an ugly version of mortality. HD destroys people’s humanity, frequently reducing patients to shaking, emaciated, wheelchair-ridden bodies unable to communicate with others. It’s like looking at death in slow motion.

Indeed, in remembering loved ones lost to HD, family members often refer not to the date of death, but the time of the onset of HD symptoms. I know that I lost my own mother, who died of HD in 2006, many years before that.

But the stigma derives not just from HD’s destructiveness. Different people in different times and places have reacted to the disease according to their circumstances and the beliefs of their communities about disability, science, and human nature. The stigma becomes hard to wipe away because it is part of the way people have learned to think and feel about HD, as taught by their families, doctors, schools, and government.

A new book uncovers prejudices

For the first time, a new book explores the roots of HD’s stigma. Written by historian Alice Wexler, it is titled The Woman Who Walked into the Sea: Huntington’s and the Making of a Genetic Disease (Yale University Press).

Many will recall Alice as the author of Mapping Fate: A Memoir of Family, Risk, and Genetic Research (1995), in which she chronicled her mother’s demise because of HD and her dynamic family’s quest for a cure. Starting in the late 1960s her father, the late Milton Wexler, became a national champion of HD research, and her sister Nancy Wexler, a top scientist, helped pioneer the Genome Project and the discovery of the HD gene in 1993.

Like so many of us, Alice, too, is at risk.

In The Woman Who Walked into the Sea, Alice explores how Americans over the past two centuries dealt with and interpreted HD. Although people in the early 1800s did not know what caused St. Vitus’s dance – as HD was then known – they understood that it ran in families. Some people with HD faced prejudice, but others were tolerated in their communities. Contrary to popular images of the disease, a number of HD-affected individuals achieved local prominence and great respect, as Alice explains.

However, today’s HD-affected families also will be all too familiar with the portraits and struggles depicted. For example, on a summer night in 1806, Phebe Hedges, a 40-year-old woman from East Hampton, New York, walked into the sea in an act of suicide. Remembering doctors’ failure to understand my mother’s condition, I found it painful to read about past families’ experiences with clinicians who were unfamiliar with HD’s symptoms or who refused care and instead urged affected families to avoid marriage and having children.

Instead of following the standard line about heroic researchers, Alice spends much of the book focusing on the challenges faced by the families.

The ambiguous Dr. Huntington

Thus the American physician Dr. George Huntington (1850-1916) appears in the book as a very ambiguous figure. On the one hand, he was the first scientific observer to note that HD involved what would eventually be called “dominant inheritance” – in other words, that a child of an affected parent had a 50-50 chance of inheriting the genetic defect and that the disease disappeared in the branch of a family where a particular parent did not have it. As a result, after the publication of Dr. Huntington’s findings in 1872, St. Vitus’s dance quickly became known as Huntington’s chorea – “chorea,” of course, meaning the shaking produced by the disease. (“Chorea” later gave way to the word “disease” when it became clear that HD also involved cognitive and other problems.)

On the other hand, Dr. Huntington used the concept of “insanity” to describe the depression and difficulties in judgment resulting from HD. That emphasis, Alice asserts, “introduced a term with powerful negative associations” and “may have heightened social fears surrounding the disease.” Scientists classified Huntington’s as a “degenerative disease,” reflecting not only its neurological reality but beliefs in social Darwinism, survival of the fittest, and the concept of a superior race.

Despite the importance of his discovery, Dr. Huntington showed no interest in carrying out further research. The Woman Who Walked into the Sea teaches us that, in the late 1800s and early 1900s, many other scientists were involved in discussions about HD, both positive and negative. Understanding the disease was a collective, international effort.

As the field of medicine modernized in the late 1800s and created the new specialty of neurology, Huntington’s was transformed from a “medical curiosity” into an “interesting” disease, Alice observes. Because of HD’s genetic cause and consistent symptoms, many neurologists came to see it as the “neurological disorder par excellence.” Research on HD broke new ground in the history of medicine. It helped to disprove the widely held belief that acquired – not genetic – influences could be passed on to the next generation. Understanding that a disease could have a specific genetic cause invalidated the belief that a person’s “weakness” or generalized tendency to illness could degenerate into any number of diseases.

Eugenics and sterilization

However, scientific progress, combined with an exaggerated emphasis on survival of the fittest, fostered extreme measures against people with disabilities. Long before Nazi Germany, the United States embraced eugenics, the idea that society should improve its genetic stock by preventing the unfit from having children. In 1907, Indiana passed the first legislation legalizing sterilization of inmates in public institutions. Over the next three decades, our country produced the harshest eugenics laws in the world outside those implemented by the Nazis.

Families with HD bore the brunt of eugenics. Alice describes the work of Dr. Elizabeth Muncey, a federal Eugenics Record Office researcher who compiled information on more than 4,000 people, past and present, who were linked to Huntington’s.

“Muncey was doing science, but also surveillance,” Alice writes. “She was scrutinizing certain families, diagnosing and labeling them, and in this manner, setting them apart from their neighbors. In this environment, her questioning, not only of the affected families but of their neighbors, ministers, and physicians, as well as town officials, inevitably put the families on display in a way that they had never experienced before.”

Alice Wexler

Charles Davenport, a scientist who worked with Muncey and analyzed her data, concluded that “it would be a work of far-seeing philanthropy to sterilize all those in which chronic chorea has already developed.” It was the government’s job “to investigate every case of Huntington’s chorea that appears and to concern itself with all of the progeny of such.” A government that failed to prevent the spread of Huntington’s was “impotent, stupid” and invited “disaster.” And immigrants with Huntington’s should not be allowed into the country. Davenport called for developing a predictive test for Huntington’s for eugenic purposes.

In the 1930s the Nazis may have forcibly sterilized as many as 3,500 people affected by HD. Tens of thousands of Americans were also involuntarily sterilized between the 1920s and 1960s, some of them perhaps affected by Huntington’s.

A long life for historical fictions

Alice illustrates how the scientific theories of the early 1900s, although eventually rejected, endured in our culture as beliefs held by everyday people. This deepened the stigma of HD. For decades, doctors continued to recommend against marriage for families affected by HD. Sadly, rather than researching ways to alleviate the disease, the scientific and medical communities advocated control of the families.

Fear about Huntington’s reached a crescendo in the 1930s and 1940s. New theories emerged, claiming that the original sufferers of the disease had been accused of witchcraft and had even played a part in the famous Salem witch trials of 1692. Both respected scientific journals and the popular magazine Literary Digest published articles on the alleged witchcraft connection; the Digest referred to HD as “the witchcraft disease.”

Not until 1969 did others debunk these “historical fictions,” as Alice calls them, adding that one perpetrator still clung to them as recently as the 1980s. Alice states unequivocally: “I have found no credible examples of an individual accused of witchcraft who behaved in ways evocative of this disease.” Even some people in the HD community still subscribe to the witchcraft theory as a way of highlighting the status of affected individuals as victims of oppression.

Time for indignation and action

The long history of prejudice and misunderstanding about HD reconstructed in The Woman Who Walked into the Sea will make you indignant, no matter what your relationship to HD. Alice’s book provides important information for scientists, activists, and families involved in the search for treatments and better care for people with neurological diseases. She shows us that disease is not just a question of science and medicine, but also of history and the cultural codes that we all live by.

As a gene-positive individual and activist, I will use The Woman Who Walked into the Sea to explain to our community and to others why the disease has so long been stigmatized and shrouded in mystery.

It also will help combat the stigma today. As Alice so expertly illustrates, substituting “fact” for “superstition” does not always lessen stigma and prejudice: at first, modern science actually increased prejudice via the practice of eugenics.

Recently I read a reader’s comment on a newspaper website asserting that it was wrong for a couple facing HD to have children. It angered and saddened me. Today we have genetic testing for HD, but, thankfully, the decision to go through with it lies solely with the at-risk individual. The information is confidential. We also have pre-implantation genetic diagnosis (PGD), which permits a couple to select a non-HD-carrying embryo for in vitro fertilization.

My wife and I tested our own daughter, conceived before PGD was available, while still in the womb. She is negative for HD. We wanted a child, even though we knew that my own gene-positive status meant I could soon become disabled. The history of HD as recounted in The Woman Who Walked into the Sea warns us of the need of HD families to assert their rights to have children and to guard against discrimination.

We know that we can shape a better future for ourselves by advocating for better understanding of HD and, as Alice urges, demanding that the medical and scientific communities use new biomedical knowledge to benefit families. This means getting involved in advocacy and politics. Many people may find this distasteful or difficult, but unless we do so, we run the risk of facing new versions of the HD stigma.

Huntington's disease, destroyer of families

When my mother died of Huntington’s disease 28 months ago, she became but the first victim of the disease in our family.

The stark truth of HD’s reach into our lives came down like an anvil on my head when I received a surprise phone from a social worker, who told me that my 80-year-old father might have to be admitted to the geriatric psychiatric ward of the hospital back in my hometown. Someone at the Veterans Administration, where my father has occasional medical appointments and picks up his discounted medicines, had filed a complaint with Adult Protective Services, the agency that looks after adults who are neglected or unable to take care of themselves.

When the social worker looked in on my dad, she saw him talking to my mother’s wedding picture, turning on the television for it, and checking frequently to make sure that “she” was okay.

My father started caring for the picture around the first anniversary of my mother’s death, about 16 months ago. He sometimes takes it with him in the car and to my sister’s and friends’ homes, and he hangs a decoration on it.

“You know that it’s just a picture, don’t you?” my relatives and I always ask him. He readily responds yes.

HD wiped out the ‘golden years’

After 48 years of marriage and 15 years of caring for my mom after her HD became full-blown, it’s understandable that my dad would develop an attachment to her photo. He’s especially lonely because I live thousands of miles away and because he has relatively little contact with my sister, her husband, and their three sons. According to my sister, he became alienated from them in part because he had dedicated himself fully to caring for my mother and had no time for them. He has nobody to help him with the grieving process.

My father had remained quite alert while my mother was alive, but he has declined physically, mentally, and emotionally since her death. He does not eat properly, has lost weight, and has several serious health problems. In addition, his short-term memory has severely deteriorated, and he often becomes disoriented. He refuses to even discuss an assisted living facility, so as a stopgap measure late last year we arranged for caregivers to come into the home for a couple hours three times a week. Early this year he fired them, claiming they were too expensive. He is stubborn, proud – and unaware of his changing circumstances. When I continue to press upon him the need for assistance, he becomes angry and defensive and says, “I don’t need any help!”

My mother was only 68 when she died. I had always assumed that she would be his caregiver someday, and that he would die first. Huntington’s disease reversed their roles and robbed them both of their “golden years.” Instead of trips and time with the grandchildren and friends, they struggled together with her decreasing ability to walk, talk, and eat. Slowly my mother became but a faint shadow of her once vital self.

Avoiding the lock-down

The social worker arranged for counselors to come to my father’s house to evaluate him. It was a Friday afternoon, and they would arrive at 10 a.m. on Monday. Because I was preparing to hire a geriatric care manager to keep watch on my dad and his health, I tried to negotiate with her to postpone the meeting for at least a few days. But she was adamant: she was concerned about my father’s safety. A lawyer urged us to “play along” with Adult Protective Services, because it has lots of “authority and clout.” I finally convinced her to hold the meeting at 3 p.m., when my sister and others could be present.

I learned that my dad could be in the hospital for as long as ten days. Worse yet, the geriatric psych ward was a so-called “lock-down” facility: he would not be allowed to leave. If they found him incompetent, he would go immediately to a nursing home or similar facility. Depending on the availability of beds, we might not even have a choice of location.

I feared a devastating shock to my father’s fragile emotional state. The first night of the crisis I stayed up until 2 a.m. on the computer researching the law and potential solutions to my dad’s plight.

That night I had a vivid dream in which my father – the man who had guided me through so many of life’s challenges – led me through a desert filled with vipers, a white bobcat, and other threatening animals. I in turn helped him navigate the same dangers.

Rallying the family

I considered flying home but, given the precious little time before the meeting, decided it was best to work the phones to rally family members (including a cousin who’s an attorney) and discuss the predicament with a geriatric care manager, who was already familiar with my dad’s situation.

My sister and five other people representing our family attended the evaluation. I believe that the show of solidarity with my father convinced the counselors that he did not need immediate hospitalization.

But there is no doubt that my father needs immediate help in many other ways. The counseling agency will arrange to spend several hours with him three times a week, and he will start getting Meals on Wheels. We need to stop him from driving and start making plans for an eventual move to an assisted living facility.

HD’s many victims

Like my dad, my sister and I are stoic about life and really good at denial, too. But we’re forced once again to stare Huntington’s disease in the eye. Instead of enjoying our father’s final years, we’re constantly reminded of my mother’s illness and his loving, heroic, and tragic attempts to deal with it. We see how sad and run-down he has become after the long fight against HD.

So we are victims too. My father’s episode reminds me of my own gene-positive status and the likelihood that I will follow in my mother’s footsteps. My sister, who is 46, is untested, and she and her husband wonder about the status of their sons. My wife stands by helplessly as she worries about me and what her own life will be like when my inevitable symptoms start and I can no longer be the dedicated father I have been to our daughter, now eight years old.

HD is more than a disease. It is a destroyer of families. And that is all the more reason why we must stop it.

Building a ‘laser-guided missile’ to attack Huntington’s disease

Isis Pharmaceuticals, Inc., a world leader in developing technology to attack the genetic causes of diseases, is now engaged in the fight to stop Huntington’s disease.

In previous entries in this blog I outlined the basics of the project (click here to read more) and expressed my enthusiasm for its potential to control HD (click here to read more). Isis aims to block HD at its genetic root, and, if all goes as planned, the company will be ready to test a drug in humans by late 2010.

On April 9 I visited Isis in Carlsbad, California, to meet the people who are seeking to relieve the suffering of tens of thousands of Huntington’s families and prevent the disease from destroying the brains of people like myself who have tested positive for the defect but not yet shown its most obvious symptoms of shaking limbs and dementia.

A new technology

“We have a technology that prevents the huntingtin protein from being expressed. We showed in cells and animals that we could inhibit mutant huntingtin,” said C. Frank Bennett, Ph.D., senior vice president of research at Isis. “If you don’t express the mutant form of huntingtin, you can abrogate or delay the onset of the disease.”

Isis developed that technology in a feasibility study carried out two years ago for Cure Huntington’s Disease Initiative, Inc. (CHDI), a Los Angeles-based non-profit foundation dedicated exclusively to finding a treatment or cure for HD. Isis demonstrated that it could block the action of the huntingtin gene in mouse and human cells and in actual mouse brains. All humans have two copies of the huntingtin gene, the recipe from which they make huntingtin protein, but in some people one copy of the gene has a mutation that makes a faulty protein, which causes Huntington’s disease. HD is a genetic disease. Children of affected people have a 50 percent chance of inheriting the mutation, and everybody who tests positive for the defect will eventually develop HD.

In October 2007 Isis and CHDI announced the current project, which seeks to control the mutant form of huntingtin in humans. CHDI will provide Isis up to $9.9 million to carry out the various stages of the project over the next three years. CHDI receives support primarily from an anonymous donor (the High Q Foundation) and is also supported by the Huntington’s Disease Society of America and the Hereditary Disease Foundation.

The weapon: big molecules called ‘oligos’

Scientists refer to this approach as “antisense technology.” DNA, the building block of all life, runs our cells by telling them which proteins to make. It does so by sending messages via another molecule called messenger RNA. As encoded by DNA, RNA has a very specific template, somewhat akin to a unique electrical outlet into which only a unique plug can fit. RNA is known as a sense molecule, and Isis manufactures the antisense plugs to control them. These antisense molecules are called oligonucleotides, or oligos.

“Our technology allows one to basically, with a laser-guided missile, target that specific messenger RNA that causes a particular disease and kill it or take it out of the body so that you don’t produce that messenger RNA,” Dr. Bennett explained about the project’s goals. “The result is that you prevent the bad protein from being expressed…. We’re designing oligonucleotides that will bind to the huntingtin messenger RNA, and upon binding to the messenger RNA, prevent it from being translated into a protein product.”

Frank Bennett, Senior Vice President of Research, Isis Pharmaceuticals

Dr. Bennett, who has published more than 90 papers in the field of antisense research and development and has more than 100 issued U.S. patents, likened the manufacture of oligos to playing with Tinkertoys.

Remember that Tinkertoys have circular pieces of wood with holes into which a child puts pencil-like sticks and thus builds a small structure. Isis does the same thing using a complex piece of machinery and produces extremely long molecules. “We do that with chemistry on a machine called an oligonucleotide synthesizer,” he said. Isis can make just a few milligrams of oligos for initial testing and then much larger amounts using much larger machines in order to prepare the oligos for commercial application in partnership with a larger pharmaceutical company.

Fine-tuning the approach

Many researchers are looking at antisense technology for a variety of scientific and medical applications. However, in a field that once had other competitors, Isis is now the only company in the world working with its particular kind of antisense technology, and it has a number of patents for its oligo designs.

Isis’s strength lies in its ability to “measure RNAs in cells,” Dr. Bennett continued. Isis has a room with “rows and rows” of instruments for studying the RNA, “as well as robots that extract the RNAs from cells and put them on machines. We have really industrialized that part of the process.” According to Janet Leeds, Ph.D., CHDI’s director of pre-clinical development, the point person for the Isis project, and a former eight-year employee of Isis, the company has decreased the cost of producing oligos tenfold.

Isis is currently working on fine-tuning the oligo it developed in the feasibility study and has already tested over 200 compounds, said Dr. Leeds. Once the best match is found, it will test the oligo in transgenic mice provided by CHDI. Developed by Dr. William Yang of the University of California, Los Angeles, those mice are engineered so that they have both a normal mouse huntingtin gene and a mutant copy of the human gene. They develop Huntington’s-like symptoms. Isis employs a special clamp known as a stereotactic device to inject drugs into mice at exactly the same spot each time, and it uses other devices to measure the mice’s behavior, muscle strength and coordination, and brain function – all crucial factors in Huntington’s disease.

If mouse tests are successful, Isis will repeat the experiment in monkeys to better assess the safety of the oligo for testing in humans.

“We’re breaking ice in learning how to modulate huntingtin,” Dr. Bennett continued. “Nobody’s had a technology that would allow you to address what is the function of huntingtin in a developed organism. It clearly plays a role in normal physiology. It’s not well understand what that role is, but it seems to be important for some aspects of normal function of neurons as well as other cells in the body. It’s expressed everywhere in the body, not just in the brain.”

Making a safe drug

Now that Isis is close to an oligo, it faces two other huge challenges. First, because the oligo would regulate both normal and mutant huntingtin, Isis and CHDI must determine how much huntingtin should be controlled in order to reduce the effects of the disease, avoid adverse effects, and lessen the chances that gene-positive people start having symptoms. For now the plan is to reduce or “knock down” huntingtin’s action by about 50 percent, said Dr. Leeds.

“That’s no different than any other drug that we use today,” Dr. Bennett said. “Say if you take a drug that lowers your blood pressure. If you’re hypertensive, and are at risk for cardiac dysfunction, because you have high blood pressure, lowering your blood pressure is good. But you don’t want to lower it to zero! All drugs will produce toxicity if you overdose. The animal models will be very instructive for giving us that guidance, because we will be able to lower the normal level of huntingtin as well as mutant huntingtin and cover whatever are the potential adverse effects of that.”

Dr. Leeds added that the Isis scientists could end up discovering that each individual needs a particular molecule to regulate his or her level of huntingtin. But this “personal medicine” approach is not yet feasible.

Getting the remedy into the brain

Secondly, Isis must get the oligo into the brain.

CHDI is banking on Isis’s success in developing the world’s first antisense drug clinical use, Vitravene, which is used to treat an eye disease associated with AIDS. Vitravene is injected directly into the eye. With current technology an oligo for Huntington’s disease cannot be delivered via a pill or injection into the brain, and any medication will have to cross the blood-brain barrier.

In the mouse experiment Isis inserted pumps under the animals’ skin and ran a tube into the brain. For humans, they are considering the use of a hockey puck-sized pump placed in the abdomen, which would pump the drug through a tube carefully inserted into the brain. Dr. Bennett pointed out that people with a number of conditions such as chronic back pain or diabetes already use commercially approved pumps. Doctors can use infrared signals to program the pumps and control the flow of medication and can inject a new supply into the pump through a port just under the skin.

“It’s obviously not ideal, but considering the severity of this disease, it’s well worth the inconvenience that these pumps produce,” Dr. Bennett observed. “Once patients acclimatize to them, they’re really not that bothersome.”

Isis is exploring the possibility of pumping the oligo into the spinal fluid. From there it would diffuse into the brain. This method might use a less invasive pump system.

Dr. Leeds pointed out that CHDI and another company are exploring a third method of delivery: a subcutaneous shot (just under the surface of the skin). A person would receive such a shot about once a month. This technology, however, could be at least a decade off. The longest term goal would be to develop a pill.

Regardless of the method, the patient would have to take the medication for life because of the genetic nature of HD, said Dr. Leeds.

Isis Pharmaceuticals’ unique flavor

Scientists began working with the concept of antisense in the 1970s, and in 2002 they discovered that oligos actually exist in nature and provoke RNA interference (RNAi). Other researchers are seeking ways to use RNAi to treat diseases, including Huntington’s. “Antisense is like a fruit,” Dr. Bennett explained. “We have apples, oranges, and pears. There’s well over a dozen different mechanisms by which you can exploit antisense to modulate gene expression.” For the Huntington’s disease project Isis is employing a particular enzyme involved in the cell’s normal RNA processing, called RNase H.

“We as a company are broadly exploiting all types of antisense,” Dr. Bennett said. “We have a little bit different flavor that we are using for this project, because in our opinion it’s working more efficiently and it’s ready for testing in man today.” The key to understanding the different “flavors,” he added, is to understand that different enzymes block or degrade the RNA in different ways. Whereas RNAi molecules are twice as large as the Isis oligo and do not enter a cell as easily, the Isis product gets into cells without a special formulation.

If all goes as planned, after the monkey study Isis will apply for permission from the U.S. Food and Drug Administration to administer a test in a small group of humans. Following that step the company would seek a partnership with a commercial drug company to run a large-scale clinical trial. Isis will count on CHDI for establishing contact with a larger pharmaceutical company and designing an efficient large clinical trial. The Huntington Study Group’s “Predict HD” program, which tracks the health of people over 18 who have tested positive for HD but not yet developed symptoms, will be an important source of assistance in a large clinical trial, Dr. Leeds said.

The company’s potential

Isis, a publicly traded company which has about 300 employees, will have as many as eight people working on its HD project, including chemists, biologists, specialists in pharmacokinetics (measuring the drug in tissues), toxicologists, and specialists in clinical trial development.

In addition to Vitravene, the company is developing Mipomersen, an antisense drug targeted at people with extremely high cholesterol levels (500 and higher). Known as familial hypercholesterolemia, this condition is similar to Huntington’s disease because of its roots in a genetic defect. It is also possible that the drug could also be used for others with high cholesterol. Dr. Bennett is confident that Mipomersen will reach the marketplace.

Isis has also used an antisense drug to reduce the effects of Lou Gehrig’s disease in test rodents. Isis delivered the drug, ISIS 333611, directly into the rodents’ spinal fluid via an implanted pump. The company is also starting a new project on Parkinson’s disease.

Frank Bennett with just a few of Isis's more than 1,500 patents.



Not a ‘cure,’ but a historic step for science and patients

Like all other scientists, Dr. Bennett hesitates to refer to the potential HD antisense drug as a “cure.” “I don’t think we’ll cure the disease,” he said. “But what I think we may do is benefit the patients so that either we stabilize the disease and they don’t get worse, or we slow the decline…. That would be a fantastic outcome.”

If the CHDI-Isis project is successful, it would be the first time that humanity brought a neurological disorder under control. According to Dr. Bennett, such a result would validate the large investment that science has made in recent years to understand how these diseases come about.

Isis, which began in 1989, has yet to turn a profit but has almost a half billion dollars in the bank for its operating expenses. It expects to have a respectable operating loss of only $15 million for 2008.

“We do this for the patients,” Dr. Bennett said. “These are diseases where there really isn’t much to offer those patients. We’re very motivated to provide therapies for those patients. Ultimately if we help the patients we’ll help the company. I’m paraphrasing – the CEO of Merck actually said this 40 years ago: ‘If you focus on the patients, the rest of it will fall in place.’ I truly believe that.”

(Next time: an at-risk person’s inside look at Isis)

Observing the cure in progress

In a couple of hours I will tour the innards of the company that could save me from the ravages of one of the cruelest diseases to afflict humanity, the disease that took my mother’s life two years ago and which will very likely destroy my own brain.

Isis Pharmaceuticals, Inc. of Carlsbad, California is working to develop a drug that will halt Huntington’s disease at its root cause: the genetic process leading to the making of bad proteins that somehow kill brain cells.

By visiting Isis I’m trying to tackle HD head-on by learning yet more about the disease and then hoping to inform the HD community of this potential scientific breakthrough.

Genetic pioneers

I want to walk in the midst of scientists who, whether they think about it or not, have my life and the lives of hundreds of thousands of at-risk and affected HD people around the world in their hands. I want to meet the men and women who could be the heroes for the families who are struggling so valiantly against HD but who are powerless to stop its genetic onslaught. The people at Isis are the genetic pioneers who could introduce us to a whole new vista of hope and health.

I want to witness firsthand the making of what would be a miracle for the HD community – and millions of people affected by numerous other neurological diseases.

I want to observe the cure in progress.

Making sense of antisense

Yesterday I prepared for the visit to Isis by interviewing Dr. Janet Leeds of the Cure Huntington’s Disease Initiative, Inc (CHDI). CHDI is funding the Isis project, and Dr. Leeds is the project’s scientific manager. We discussed the two biggest challenges of the project: first, administering a drug that will not interfere with the normal function of the huntingtin gene (a gene that everybody has but which has gone awry in HD people) and, secondly, delivering the drug to the brain.

I also learned that scientists have been thinking about the technology being studied by Isis – a technology to make an antisense drug – since the 1970s, and not only since 2002, as I wrote in my previous entry here.

So I spent a part of the evening studying a report from Isis that describes the similarities and differences between antisense technology and a more recent technology, developed after the discovery of RNA interference in 2002. I hope to learn more about these two technologies today.

Wanting to help

The attempt to grasp all of this technical information and the anticipation about my visit to Isis caused me to sleep fitfully last night. I dreamt that I had to make a presentation to Isis scientists that would convince them to hire me to help them market their firm to the world. They were highly skeptical, but then I gave a passionate speech about the need to relate to people on a human level. They began to listen.

I am not a scientist, but I urgently want to help in the effort to cure HD. I depend on the cure, and so do my wife and daughter. I refuse to let this disease ruin my life and prevent me from seeing my daughter grow up.

Time for optimism: a cure for Huntington's could be near

On October 26, 2007 a California pharmaceutical company announced a multi-million-dollar project to develop a drug that would eliminate the root cause of Huntington’s disease.

If it works, the project would not only cure Huntington’s but could revolutionize treatments for other diseases and usher in a new era of medical advances that just a few years ago seemed like science fiction.

Isis Pharmaceuticals, Inc., located in the San Diego suburb of Carlsbad, revealed that it is working on an antisense drug for HD. This class of drugs is designed to block the action of genes that cause disease. In the case of HD Isis aims to stop the huntingtin gene from making proteins that disrupt brain cells and cause the harmful symptoms of HD.

An impressive development

In my opinion this is the most impressive and promising initiative ever developed for finding a treatment or cure for HD. Isis is aiming for results now and in humans, not just in a test tube or in a mouse.

The technology is based on the discovery of RNA interference, or RNAi. RNAi is a natural process in which genes are switched off. Its discovery was considered the top scientific breakthrough of 2002, and scientists have been studying it intensively ever since. So are some drug companies.

Isis has already gotten approval from the U.S. Food and Drug Administration (FDA) for Vitravene, which it calls the “world’s first antisense drug” to go to market. Vitravene is used to treat an eye disease associated with AIDS.

And Isis has used an antisense drug to reduce the effects of Lou Gehrig’s disease in test rodents. Isis delivered the drug, ISIS 333611, directly into the rodents’ spinal fluid via an implantable pump.

A pump in the brain

I have long imagined that this could be the future for me and many hundreds of thousands of other people around the world who are gene-positive for HD: we would have a small pump on or in our heads delivering a life-saving drug to our brains. HD would be totally controlled.

Such pumps now exist because of nano-technology and have actually been used safely in thousands of people. Doctors surgically insert the device into the brain. They inject medication into the brain during a routine visit to the doctor’s office.

It is especially encouraging that Isis has already shown that it could reduce the action of huntingtin in the brain and peripheral tissues of normal mice using an antisense compound.

$9.9 million in funding

The Isis research is backed by the Cure Huntington’s Disease Initiative, Inc. (CHDI), a recently founded drug discovery firm targeted exclusively at HD and funded by a private, anonymous donor. Based in Los Angeles, CHDI will provide Isis up to $9.9 million for the project. This is one of the largest amounts – if not the ­largest – ever spent on an HD research project.

The project will first focus on testing an antisense drug in transgenic HD mice – genetically engineered animals that have the same genetic defect as human HD patients. If successful, Isis will then test the drug in monkeys. CHDI could then approach the FDA for approval for human testing as early as the third year of the project.

“This is very good news because a potent RNA drug will stop Huntington's at its source, and we could let ourselves say the ‘cure’ word,” Dr. LaVonne Goodman, the founder of Huntington’s Disease Drug Works and an expert on HD research, wrote shortly after the Isis announcement. “I confess that just a year ago I didn’t believe I’d see this much progress on RNA therapy in my lifetime, and I’m glad I’m wrong.”

Reversing HD’s devastating effects

If successful, the Isis antisense drug could very well do more than prevent HD: it might also partially reverse the disease. Studies of RNAi treatment in mice have shown that the animals recovered normal motor function because of the ability of brain cells to regain health and take over the job of cells destroyed by HD.

This possibility brings me a mixture of joy, frustration, sadness, and guilt. I am excited to know that if my own symptoms start soon, the potential Isis drug may be able to stop them and keep my brain completely healthy. And I am happy that acquaintances with HD might return to a normal life and save their families from witnessing their horrible decline. But I also wish that such promise had existed two years ago February, when my own mother died of HD.

I learned about my mother’s HD in 1995, and I tested positive in 1999. Living at risk for HD – a 100-percent genetic disease that affects all gene-positive individuals – has impacted every aspect of my and my family’s lives. It has been extremely frustrating to see scores of theoretical advances over the years but no real hope of an effective treatment.

Time for optimism

Now, for perhaps the first time, I am beginning to feel optimistic about my future and that of the HD community. As I wrote recently (click here to read more), in December the state of California moved a step closer to considering a multi-million-dollar project to create a program to seek a treatment for HD using stem cells. Other scientific breakthroughs continue to occur.

I have felt especially moved to express optimism because in the last few days I have felt deeply sad at reading about young people with HD at the new website WeAreHD.org. They are struggling with symptoms and worrying about the fate of their potentially at-risk children.

The HD community needs to support the Isis-CHDI partnership in any way it can. I will visit Isis very soon to learn more about its HD project, so please stay tuned for a new entry on this extremely important topic.

Keeping calm in the face of Huntington's

Living at risk for Huntington’s disease often causes me to try too hard to take care of myself. I’ve always been a bit of a hypochondriac and face the possibility of other health problems, so living with a positive test for HD can greatly magnify my concerns.

Just recently a chain reaction of self-inflicted and misunderstood incidents landed me in the operating room.

Weighing the risks of supplements

About three years ago, I started taking the supplements recommended by the Huntington’s Disease Drug Works program. They are tolerated well by humans and have shown positive results in animal tests, and, significantly, those people with early or mid-stage HD who consistently take them have stabilized or improved. I am hoping that they will delay the onset of my symptoms, which are inevitable because of HD’s 100-percent genetic nature.

As one should do with any supplements, I have carefully followed the instructions. With creatine, for example, I get periodic blood tests to check for possible harm to the kidneys.

Another of the supplements is trehalose, a natural sugar. I take it mixed in water, plain yogurt, or cereal.

Trehalose seemed harmless and I didn’t think it would cause any side effects. In contrast with my concerns about creatine, I took it without thinking about the possible consequences.

But then early last fall I got a call from a nurse at my health plan stating that I should see my physician because one of my blood tests showed a glucose reading of 109 – nine points above the recommended maximum. I learned pretty quickly that 109 put me in a category known as “pre-diabetic.”

“Diabetes?! I have enough to worry about with HD!” I told my wife. There is no history of diabetes in my family, and I usually keep very close to my recommended weight range.

Dr. LaVonne Goodman, the founder of the Huntington’s Disease Drug Works program, reminded me that the instructions for taking trehalose include reducing my carbohydrate intake. After all, the nine standard-size packets of the sugar were the everyday equivalent of three soft drinks.

Panicking about carbs

For the first time I started paying attention to the carbohydrates in my diet. “Carb counting” is a big new fad in our culture. My wife did it when she took part in a weight reduction program. These days carb stats seem to be on every food label and every restaurant menu.

I did not know the actual cause of my glucose reading. Was it the trehalose? Was it the fact that I had gained twelve pounds over the summer and had gotten out of my exercise routine? Was it a lab mistake or maybe just a fluke reading? Had I crossed some artificial barrier established by a drug company interested in classifying more people as diabetic? Did the reading result from some combination of factors? Both Dr. Goodman and my own physician actually expressed little concern about the number.

Whatever the cause, I panicked. I simply could not accept having another major health threat to worry about. I wanted to cut my carbs and lose weight.

I immediately eliminated practically all carbs from my diet – no bread, no dough, no candy, no corn, no potatoes. I tried to eat just proteins, vegetables, and salads. I had an especially hard time turning down pizza. But I was determined to escape from the “pre-diabetic” range.

From bad to worse

In my worst imagination I could not have imagined the terrible result of this strategy. My stools became rock-hard, and my bowel movements, which have worked excellently throughout my life, turned into an ordeal. Blood started showing up on the toilet paper. I figured the cause was hemorrhoids that occasionally flare up, which I usually treat with some over-the-counter suppositories.

Then one night a large amount of blood came out, leaving a very long streak in the toilet bowl. It must have been close to a tablespoon’s worth. The doctor at the proverbial urgent-care clinic examined me, saw hemorrhoids, and prescribed a medication. It did not work. The bleeding continued, and now I had pain. Several weeks later I returned to the clinic. This time I heard another diagnosis: the doctor said I probably had an anal fissure produced by the hard stools and that it might require surgery.

Anal fissure?! That was a completely new term for me. Surgery?! My fears multiplied. I quickly learned that anal fissure surgery had a high success rate, but in some cases the patient ended up with uncontrollable flatulence or, worse yet, had to wear diapers the rest of his or her life because of anal dripping.

And, I was told, surgery involved general anesthesia. I wanted to avoid this option at all costs, because I had heard stories over the years of people at risk for HD suddenly experiencing their first serious symptoms or seeing their symptoms worsen because of shocks to their bodies such as car accidents.

Staving off surgery

I tried a cream on the fissure with no luck. A surgeon prescribed stool softener, several warm baths per day, and nitroglycerin ointment, used to promote blood circulation and healing in the anal area. He told me to try this treatment for two months.

The pain became excruciating – like a knife cutting into my anus. The doctors I spoke with said it was one of the worst kinds of pain. Every bowel movement caused the fissure to reopen. The pain usually lasted for hours and sometimes as long as half a day. I could not sit comfortably. I did not feel like talking to anybody, and I couldn’t find the energy to blog here except for one important entry in late December (click here to read it). One night I had to eat dinner standing. I became very irritable towards my wife and daughter. Sometimes I felt on the verge of fainting.

The nitroglycerin did not help. I sought a second opinion from another surgeon, who sometimes did Botox injections into a patient's anus as a way of relaxing it and allowing the fissure to heal. But she recommended I have the surgery. And – very important for me – she said I could do it as an outpatient and with local anesthesia.

The procedure, which took place on February 8, immediately relieved the pain, and my recovery went well. Now, for the first time in five months, I am no longer afraid to go to the bathroom.

Valuable lessons

I have learned some valuable lessons from these past few months.

The terrible pain and my subsequent recovery have reminded me once again to savor every moment of life.

It also reminded me that living at risk for or having HD does not exempt people from other health challenges. I know of at least two women who have also had to battle breast cancer.

Just as with standard medications, taking supplements is a serious matter that requires extra vigilance regarding diet and other habits. It actually took me a year to start taking the supplements, and I phased in one after the other.

However, in my case, because I have not revealed my at-risk status to my health plan for fear of genetic discrimination, I do not have a local physician monitoring my body’s reactions as recommended by the Huntington’s Disease Drug Works. If I had, I likely would have avoided the crisis. The crisis, in fact, led me to seek out a naturopath, who has helped me take a more holistic approach to my situation of risk. Thus I am constantly juggling information from Huntington’s Disease Drug Works, my health plan, my psychotherapist, and now the naturopath.

An uncomfortable place in the system

It’s obvious that our health system is failing me. If I could give full disclosure, I could get the proper care locally. Had the system not taken weeks to properly diagnose and treat my anal fissure, I very likely could have avoided the pain and the surgery. Had the system guided me to a dietician after I tested high for glucose, I could have avoided the fissure altogether.

I’m learning not to rush into solutions. Had I not cut my carbs so quickly and drastically, the crisis would not have started. The naturopath put me on a vegetarian diet for a couple of weeks in order to help soften my stools and relieve the pressure on the fissure. That was good short-term advice. But then my wife pointed out to me that, if I stayed on a strict vegetarian diet without further consultation and study, I could be heading for a new crisis.

On a follow-up visit, my naturopath agreed and said, “Listen to your wife.” Health care – especially when one is at risk for a serious disease – is a family matter, not just an individual one.

Managing anxiety

I believe that my crisis provides me and others at risk for Huntington’s disease with one final message: keep anxiety at a manageable level. At the end of my last conversation with the naturopath I concluded that I was trying to “maintain equilibrium.” By equilibrium I mean a balance in activities and diet and proper attention to the mind and soul. Only with that approach can we muster the energy and level-headedness needed in the fight to avoid Huntington’s disease symptoms.

I recently had a new blood test. My glucose is back in the normal range. The months of pain were a high price to pay for my few days of panic. I should have acted more slowly and calmly. But that’s so hard when you face a disease like HD. As I felt relief after my operation, I yearn for a cure for Huntington’s disease so that I and so many others can lead more peaceful lives.

Stem cells: the dawn of a new era for Huntington’s disease research

The campaign for stem-cell research on Huntington’s disease took an important step forward on December 12.

The 29 members of the governing board of California’s $3 billion stem-cell institute heard from two leading HD researchers about the large potential of stem-cell research in developing treatments for HD. The presentations took place at the board’s monthly meeting, held at the University of California, Los Angeles. These influential leaders from academia, the bio-technology industry, and patient advocate groups will decide in the coming months whether a proposed California HD “disease team” will receive a $50,000 planning grant and potentially millions of dollars for an intensive, statewide effort to attack HD using stem cells.

A historic moment

For nearly an hour the Independent Citizens’ Oversight Committee (ICOC) of the California Institute for Regenerative Medicine (CIRM) watched a detailed presentation by Dr. Robert Pacifici, the chief scientific officer of the California-based Cure Huntington’s Disease Initiative, Inc. (CHDI), Dr. Hans Keirstead, a stem-cell dynamo at the University of California, Irvine, and HD activist Frances Saldaña of Orange County and her daughter Margie Hayes, one of three siblings who developed juvenile HD and the mother of two at-risk children.

Working with my fellow activists in the San Diego chapter of the Huntington’s Disease Society of America (HDSA), the Orange County affiliate, and the Los Angeles chapter, I spearheaded the organization of the CIRM’s “Spotlight on Huntington’s Disease.” Like previous CIRM spotlights on other diseases, this event was open to the public. I joined HD researchers, activists, and families from throughout southern California to provide support and witness this historic moment in Huntington’s disease advocacy.

HD takes center stage

I was especially heartened to see HD take center stage in California and hear the scientists’ optimism about stem cells for HD research. Many of us in the HD community have felt intuitively that stem cells are crucial in the search for a cure and should receive emphasis immediately. At the CIRM meeting I had the strong sensation of being fast-forwarded into a future where HD will no longer threaten the lives of people like Margie, who, her speech impeded and her body dancing uncontrollably, moved ICOC chair Robert Klein and the rest of the audience with her sad story of testing positive for HD, suffering discrimination, and becoming incapacitated.

CHDI efforts

Dr. Pacifici, whose non-profit CHDI has stepped in where the big drug companies have failed to venture, stressed the importance of stem cells in recreating the actual human version of the disease in a Petri dish. CHDI, he explained, has set up some twenty parallel programs aimed at finding treatments.

“Without exception there isn’t a program in our portfolio that wouldn’t benefit dramatically from having a stem-cell-derived cell population in its flow scheme,” he stated. HD stem cells would enable researchers to understand such puzzles as the differing ages of onset in those individuals with identical genetic defects (the so-called CAG repeats of Huntington’s disease) and whether brain cells are dying as a result of “murder or suicide.”

Significantly, stem cells would speed up the process of screening for drugs, Pacifici said.

New hope

Pacifici then offered the kind of hope that I could only dream of as my own mother withered away and ultimately died because of Huntington’s nearly two years ago – a hope that I can now cling to as I approach my own inevitable symptoms. The same cocktail of compounds used to turn stem cells into brain cells in a Petri dish, Pacifici stated, could be used as drugs to repopulate damaged areas of the brain with new cells. “It may be that we can change our aspiration from preventing or slowing Huntington’s, to actually reversing Huntington’s disease, if the promise of regenerative medicines and cell-based therapies comes to fruition,” he said.

Dr. Keirstead underscored the urgency of using stem cells in HD research and detailed how the hope can become reality.

“I was an absolute convert to HD,” said Keirstead of the request by UC Irvine colleague Dr. Leslie Thompson that he ply his internationally recognized stem-cell expertise in the area of Huntington’s. “Huntington’s disease is truly, in my opinion, one of the few diseases that’s applicable in the short-term” to two key stem-cell research strategies – using cells to understand how the disease works and to actually treat people. HD’s character as a disease with a single, discovered genetic cause and its impact on specific areas of the brain make it one of those unique candidates for stem-cell research, he explained.

Little scientific attention

Despite this enormous potential, HD stem-cell research has received little attention from the scientific community.

“It absolutely amazes me that there is not a handful – not one – human embryonic stem-cell line of HD…. Not a one in the entire world,” Keirstead stated, referring to the lack of scholarly articles on stem cells derived from human HD embryos. “That’s just remarkable. With the technologies of deriving embryonic stem cells from blastocysts [the human before it becomes an embryo], with the adoption of prenatal genetic diagnosis by many HD-bearing couples, it amazes me that we don’t yet have a stem-cell line or two or three or four or thirty or three hundred that bear this mutation, a mutation of a gene that we absolutely know of and that we have access to…. Yet we know precisely how to obtain those things. We know very routinely how to make them…. This is going to be one of the major, major tools.”

Keirstead and UCI are wasting no time in taking the lead. “We are deriving new lines at UCI,” Keirstead explained. “I have recently established relationships with fertility clinics. I now have access to over 10,000 blastocysts a month. That’s phenomenal…. We are already receiving phone calls from people with Huntington’s disease that have [gone to] fertility clinics that have HD-positive blastocysts that they would like to channel our way. I have about fourteen such individuals so far with the three fertility clinics that I am working with.”

Thinking long-term

Keirstead is a strategic thinker who sees the long-term implications of his work.

“You can’t walk into the FDA – two guys and a rat – and say, ‘Let me try this in humans,’” he said. Keirstead transforms stem cells into other cells in a manner compliant with the standards of the Food and Drug Administration and in quantities large enough to make their use commercially viable for large biotech companies. He deals in not just “a few cells in a dish,” but in the billions. Only in this way, he explained, will a company invest the many millions of dollars necessary to getting the stem-cell process to treatments. Keirstead’s work includes pushing stem cells to become neurons for the striatum, the area of the brain devastated by Huntington’s disease.

“I don’t think we should lose sight of the power of this. If we can actually make high-purity populations of striatal interneurons, what’s going to happen to this field is precisely what’s going to happen to the spinal cord field, which is: a commercial entity will come in and value-add, that more researchers will take those cells… and begin working on them in high-purity format. And we’re going to see a turning point. It’s the dawn of a new era for HD.”

Increased advocacy role

I hope that the CIRM spotlight on HD was also a new dawn for HD advocacy and Californians’ central role in it. In chairman Klein’s words, “The Huntington’s organization’s patient advocacy is extraordinary. I have tremendous respect for the passion, intensity, tenacity, and commitment of the Huntington’s organization.” Klein had earlier noted that HDSA was the only disease advocacy group to have done presentations in both the CIRM “spotlight” format and in the public hearing of the ICOC board. The previous presentation took place at the October 3 CIRM meeting in San Diego, where HDSA-San Diego president and San Diego Chargers’ public relations director Bill Johnston and his wife Ramona, who has HD, appealed to the board to support HD research.

The December 12 spotlight came just weeks after CHDI announced another stunning new project in HD research to take place in southern California. On October 26 CHDI and Carlsbad-based Isis Pharmaceuticals, Inc. revealed that they would collaborate in a multi-million-dollar effort to develop a drug to target directly the huntingtin gene, the cause of Huntington’s disease. I will write about this exciting development in a future entry.

The complications and stress of success

Living with a positive test result for the Huntington’s disease gene requires a constant juggling of life’s many demands and opportunities. What many would see as unambiguous success, for instance, actually causes new complications and stresses.

Take this blog. I haven’t posted here in several months. I would like to write several times per week. But job, family, chores, exercise, taking care of a new puppy, volunteering for the Huntington’s Disease Society of America (HDSA, www.hdsa.org) – and success – have frequently left me without time to write.

The complications of success

In the past few months, unimaginable professional success has further diverted my focus from HD. I received an all-expenses-paid three-month trip to write a book, won a prize for another book, and have garnered numerous other accolades. I’m entering the prime of my career. The joys of such achievement have occasionally allowed me to forget my mother’s death at the hands of HD last year as well as my own at-risk status.

Success has created greater opportunities, but also made HD an even bigger factor in my professional life.

For the first time in 14 years, I have the chance to move to a better job. In my current job I’ve been but a cog in a mediocre machine, while the offer of a new job would allow me to join a team of people who truly appreciate my skills and want to employ them fully in an exciting work environment. I’d gain great prestige, a position of international leadership in my profession, and a 70-percent raise. I’d ultimately be positioned for a shot at the top jobs in my field.

The decision sounds like a “no brainer” – until you consider that I very likely could develop HD symptoms in the next few years. I’m 47, and my mother’s first symptoms, emotional outbursts, probably started around that time. By her early 50s, she had chorea (shaking), had stopped speaking normally, and could no longer take care of herself.

With that possible scenario in mind, should I take on a challenging new job? Unlike my mother, I know that I’m at risk, and perhaps I can stave off the symptoms until my sixties by eating and sleeping properly, exercising, and taking supplements recommended by the Huntington’s Disease Drug Works program (see www.hddrugworks.org).

However, because HD is a 100-percent genetically caused disease, there is no guarantee that I won’t get my first (noticeable) symptoms tomorrow morning.

The stress of success

The challenges of moving my family to another state, facing a higher mortgage, starting a new job, and certainly working longer and harder hours might not be worth it, especially since stress itself might trigger or worsen symptoms.

The financial rewards become far less significant when we consider that my wife would face a $30,000 cut in salary and lose some benefits, for example, an excellent retirement that we’re counting on for our future. Those losses are outweighed by my gains, but only if I remain healthy. If we had to rely on her lower salary and my much lower unemployment-related disability pay, we might face a bigger crunch than if we just stayed put.

Because of HD, just thinking about this opportunity has generated stress and enormous pain, frustration, and outright anger. I’ve frequently wanted to blurt out to my colleagues and the interviewers, who are anxious for me to accept the offer, that I can’t easily embrace this wonderful opportunity because I’m at risk for a deadly brain disease.

Paradoxically, I’ve chosen to stay in the “HD closet” precisely because revealing my status likely would lead potential employers to discriminate against me. Legally they can’t, but, in reality, they’d avoid a job candidate who might not be able to work more than a few years.

By moving, I’d also lose connections with the local HDSA chapter and a group of caring individuals with whom I share a life-and-death struggle. I could certainly volunteer for the chapter in my new city, but I doubt whether I could have the same impact that I’ve had over the past nine years. It would take time to become part of a new team, and the demands of the new job would leave precious little time for activism.

Tough choices

I’ll be weighing the pros and cons of the job offer with my wife, close friends, and with you, my readers, in the coming weeks. Like many people affected by HD, I continue to prepare for the worst but live as best as I can. That attitude gives me eternal hope and keeps me professionally active and always in search of new job opportunities. But while I know that money and prestige are great boosts to anyone’s ego, they can’t solve the challenge of living at risk.

Giving up one’s dreams very early is one of the cruelest realities facing HD families. This hits especially hard when I think of my mother’s death at age 68 and of friends who have recently passed from the “at risk” to the “symptomatic” category. “You’re not just contemplating a job – you’re contemplating your whole life,” my wife tells me.

She believes that I am now beginning to understand her frustration at not having a second child. Having two children was her dream, but we abandoned the idea because of the stress involved in testing the child before birth – an experience we know all so well from having our first daughter, who tested negative (see my previous entry on this topic by clicking here). As my wife concludes about the dreams we’ve given up because of HD: “They’re so real and so close to you, yet they’re so far away.”

Dreaming of victory

The night after I wrote my previous entry (click here to read the article) on the New York Times’ recent front-page article on Huntington’s disease, I dreamt that the United States had won the Iraq war.

I read about it on the front page of the Times while sitting in a coffee shop. Everybody around me was reading the same page-one headlines. Next to the words was a photo of a V-E Day parade from 1945. Like the newspapers in Harry Potter movies, the picture came alive with moving cars and a soldier kissing a woman among falling confetti.

The United States was once again the undisputed leader of the world after smashing two evil powers. Nobody would mess with us as we led the world into a new era of unending peace and unbounded prosperity. I felt immense relief from the fear, unpredictability, and violence of war.

Finding the parallel

When I awoke the next morning, I knew immediately that the war in Iraq was my personal war against HD. Reading and writing about a major article on HD in one of the world’s most influential newspapers had triggered a powerful fantasy about the utter defeat of Huntington’s – another daunting effort – and the violence it wreaks on people’s minds and bodies and the lives of their loved ones.

Since discovering in late 1995 that my mother had HD, I have hunkered down in an emotional bunker. I have struggled to fight HD by dealing with my mother’s long decline and death (last year – click here to read the article), becoming an activist for the Huntington’s Disease Society of America, and wondering each day when the symptoms will start.

I tested positive for HD in 1999.

I am so fearful of the disease that I believe I must keep persistently vigilant so that it will not strike me. I put in long hours thinking about how to increase public awareness about HD and also the fundraising so necessary to keep scientists working towards treatments and a cure.

Dreaming forward

Seeing Huntington’s disease get such massive and rare publicity allowed me to come out of the bunker for a few hours to try to glimpse what my life would be without this disease.

That vivid, surreal dream and the almost indescribable peace it produced in me felt so real.

People in the HD community told me how they became overjoyed in 1993 when the huntingtin gene was discovered after years of intense research. But 14 years later we still seem so far from a cure. We’re back in the bunkers.

But we are all fervently praying and hoping for the announcement that an effective treatment or cure has been found. The defeat of HD will be a truly historic moment for a human race that seeks liberation from disease.

In the meantime, I must learn to fantasize and dream more often in order to get through the weary days of fear and struggle. And I need to channel the energy of those fantasies and dreams into the fight for a cure.

Huntington's makes page one

Today was a very important moment for building awareness about Huntington’s disease: the New York Times, one of the world’s most influential newspapers, ran a long page-one story about a young woman’s brave decision to be tested at age 23 (click here to read the article).

It’s rare that HD gets such attention. Most people have not heard of HD, or they have only a vague notion of it. Like a lot of orphan diseases, it just doesn’t register with people. After I recently wrote a friend a long letter about my own gene-positive status, his response referred to “Hodgkin’s disease.”

I myself have tried to bring HD to the New York Times’ attention. A couple of years ago I submitted an article about my experience with HD to the paper’s Sunday magazine and then to its science section, but I allegedly had nothing new to say about the disease. Luckily, in September of 2005 the Washington Post published an article about my story written by Dr. Martha Nance of the Huntington’s Study Group (click here to read the article).

So I was thrilled to see reporter Amy Harmon’s well-written portrait of Katie Moser. The article outlined the history of HD in Katie’s extended family, the pros and cons of testing at such a young age, and the ways in which Katie has coped with living at risk. Harmon especially captured the psychological trauma people experience before and after testing.

Like me, Katie Moser faces a very long road of wondering when and how her symptoms will start. As I did, she may someday face the difficult decision of testing her own child for the genetic defect that causes HD. I think about HD every day. It’s a lifelong curse on me and my family.

But is there really a trend towards increased testing among young people, as the article claims? The reporter cited no empirical evidence to back up this claim. If young people indeed do want to get tested more, it’s simply the result of the availability of a test for HD (starting only in 1993) and the recent appearance of preimplantation genetic diagnosis (the testing of embryos). Their parents could not even dream of these possibilities. Interviews with more young at-risk people, including those who have had children, could have shed more light on the purported new trend.

The article also did not discuss some other important facets of the HD story. Did Katie attempt to line up all of her insurance coverage before testing? Why does research on HD and other rare diseases receive so little funding when, especially in the case of HD, they could provide the key to curing other diseases? Why, in fact, is HD so little known and understood? And why does it carry such a horrible stigma?

I’ve been writing on HD for nearly ten years and reading about it even longer. I didn’t see anything new in today’s piece. The article could have really driven home the point that HD is one of humanity’s cruelest diseases. As a friend of mine observed, the article could have connected with more people had it explored HD more forcefully.

I make these criticisms because the paper gave the reporter more than ample space – some 4,700 words – to explore HD fully. According to her own video on the newspaper’s website, she spent a year following Katie’s life.

But I still commend Harmon and the New York Times for bringing valuable exposure to Huntington’s disease. This, in fact, is the paper’s second article on HD in recent months. On November 14, 2006 it ran an article that described the stark descent of filmmaker Chris Furbee and his mother into the hell of HD. You can read that article by clicking here.

I urge the New York Times and the media in general to increase their coverage of HD and related diseases and of medical research in general. Tens of thousands of American families are affected by HD, and many million more people will get Parkinson’s, Alzheimer’s, and other neurological disorders. Whether we realize it or not, we are all in this struggle together.

Testing a new service

Dear Friends,

I now have close to 500 people who receive news of my blog via my e-mail, stophuntingtonsdisease@yahoo.com. That's a lot of addresses for me to manage, so I am thinking of joining a service that will reduce the workload of sending out so many e-mails. Such a service would also avoid my e-mails as being seen as spam or getting stuck in people's bulk mail boxes. Right now I'm testing Feedblitz. If you'd like to help me test this service, please subscribe by putting your e-mail address into the box in the upper-left-hand corner of the blog. Once I have made a final choice as to what service to use, I will notify you so that you can subscribe. The reason I'm posting this entry is because apparently the only time Feedblitz sends out e-mails to subscribers is when there is an actual update to my blog. I don't think I can send e-mails at will through Feedblitz.

Thanks for your help!

Yours in the struggle to cure diseases,

Gene Veritas

Uncertainty and a steadfast spouse

The forgotten people in the story of Huntington’s disease are the spouses and potential spouses of those at risk. Practically all of the energy of the HD movement goes into finding a treatment to alleviate the suffering of the ill and preventing the onset of the disease among the at-risk. Fundraisers, publications, and meetings seldom address the pain of the caregivers-to-be.

A recent e-mail from one of my readers painfully reminded me of this reality. He agreed to let me discuss his situation but wants to remain anonymous. I’ll call him Ed.

A love story

Several years ago Ed fell in love with a woman whose mother died of HD. However, the pressures of living with her at-risk status led them to argue frequently. Ed feared that his girlfriend might someday test positive for HD. Their relationship soon fell apart. She did not believe that Ed could really love her, and Ed found it difficult to manage the huge uncertainty of a life with an at-risk person.

Recently they bumped into each other and had their first serious conversation in two years. Still untested for the disease, Ed’s friend had gone on with her life and achieved many of her goals. “She seemed really happy,” Ed wrote. “I tell you all this, Gene, because I want you to understand that she does captivate me and, if I am being honest, my life over the past two years has been boring without her.”

Ed’s friend hinted that she wanted more than friendship. Ed again became scared. “My greatest fear is that one day the woman I love will be transformed and will be unrecognizable,” he wrote. “I don’t know if I can commit to this life. More importantly, I cannot let her down again.”

Ed’s predicament is one shared by all couples in the HD community – intense love challenged each and every day by the harsh reality of a fatal brain disease. “I just feel muted by the situation,” Ed confided to me. “I can’t share my fears with the person that I want to. If we can’t discuss the situation and our fears, those fears will fester and prove insurmountable, even in the short term.”

Just today I received another message from Ed stating that they had once again broken up.

A special person

There are no easy answers for Ed or anybody else in a similar quandary. Many people break off a relationship when they learn that the other person could get Huntington’s disease, and some marriages end in divorce when the at-risk person becomes ill. Caring for a person with HD becomes an ever more trying and time-consuming process. Sometimes the stress severely debilitates or even kills the caregiver first.

Only a very special person can successfully navigate through the treacherous swamp of uncertainty presented by HD. That special quality includes more than love and commitment. It requires the ability to plan each day for the worst but to maintain eternal optimism about the hope for a treatment, a cure, or simply a delay of the disease’s onset.

I am thankful every moment that my wife is that person. We had been married for only three years when HD intruded on our lives. We did not yet have a child, so it would have been very easy for my wife to ask for a divorce. But I don’t think the thought ever crossed her mind. Somehow we knew we were together for life, and she remained loyal. For her the biggest challenge was not about deciding whether to stay with me, but learning how to adapt to a new reality and to make life as normal as possible in a highly abnormal and difficult situation.

Inner strength

My wife has an inner strength that comes in part from having grown up poor. When she was young her family had to sell their home, and many days there was no meat on the table. The worst part was the certainty that the next day would bring the same misfortune. She postponed badly needed dental treatments, and she started working in her late teens to help balance the family budget. She attended college at night while working full time.

Living on the edge of survival has prepared her to accept a lot of adversity – especially my positive test for HD – with great determination. Knowing that I will lose a good part of my income after I become disabled, she works full-time so that we can try to pay off our mortgage earlier and increase our savings. She knows that she will not be able to take early retirement and will have to see our daughter through college.

Every week she cooks a menu of healthy meals for me, and she takes on the burden of extra housework and childcare when I become immersed in writing for this blog or working as an activist for the Huntington’s Disease Society of America (www.hdsa.org). Every weekend she observes me as I perform cognitive tests on the Huntington’s Disease Drug Works computer program (www.hddrugworks.org). Every year we plan together how we will donate money for HD research. Whenever she hears or reads a report about breakthroughs in neurological research, she immediately notifies me.

Right after our marriage started, our lives had taken a turn for the better. We were both establishing ourselves in our careers, and we had many exciting plans for the future.

But my wife has had to postpone or simply erase from her mind the hope that we will achieve many of those goals, for example, having a larger family. Our daughter tested negative for HD in the womb. My wife has badly wanted another child, but going through the trauma of testing another child or the expense and challenges of preimplantation genetic diagnosis (testing embryos for the disease) led us to cut off that possibility forever.

My wife has given up a lot of other dreams, like buying a summer home or moving to a less expensive city. We need to invest in her future here, because this is where she has job security and a salary that probably could not be matched elsewhere.

Worry: a constant companion

More than anything else, HD has robbed my wife of the chance to live peacefully. After so many years of struggle, she now faces the biggest challenges of her life. Worry is her constant companion. Once my symptoms commence, how will she continue to work full-time, manage the household, raise a daughter, handle all of the other tasks that I have taken care of over the years such as our financial paperwork and house repairs – and care for me? How will she and I decide when it is time for me to enter a nursing home?

As my wife said after reading a draft of this article, the worst thing about HD is its timing. It hits people in the prime of life, and it robs victims of their abilities to walk, talk, eat, and think over a period of 15 to 20 years. That is a very long time for both me and my family to endure.

We don’t talk much about Huntington’s disease these days. But HD is always looming in the shadows of our life. We should talk more about it, but we don’t. We’re trying to enjoy our lives and our daughter as much as possible before the pain begins.

Deep inside, I know my wife will prevail. She is always at my side, and she will remain there as long as possible. She’ll get by somehow. But it will be lonely and arduous, because she faces losing her closest companion and her daughter’s devoted father.

Coming together

It’s been a year since my mother died of Huntington’s disease, on February 13, 2006. The call from my sister about her death came in the middle of the night, and two days later my wife, daughter, and I flew to my hometown, some 2,500 miles away, for the wake and funeral.

My mother’s death was not a surprise, because HD had caused her to decline rapidly in those final months. However, after her placement in a nursing home in August of 2005, we all had expected her to live at least two or three years more.

It took me nine months, until last October, to resume this blog (see “Mourning Mom”). Seeing my mother in a casket and facing my own situation as gene-positive for HD, I became emotionally paralyzed. Slowly, I have reengaged with my writing on HD.

A father’s visit

Now is an especially poignant moment. My father is out for a three-week visit. It’s good to have him here, and it’s good for him to be here. But his presence also conjures up difficult moments.

My father talks about my mom every day. Nights alone are especially difficult for him. My dad never cried when I was a child, but now he breaks down every night. Any 79-year-old man would suffer greatly and be frightened after losing a wife of 48 years. But it’s especially hard for my dad because, for 15 years, HD had slowly but steadily caused her to deteriorate mentally and physically. For both of them retired life became a trial to be endured rather than a golden moment to be enjoyed. Instead of taking my mom on a long-planned trip to Europe, he had to start preparing for her death.

My dad likes to talk about how he “robbed the cradle” by marrying a woman ten years younger. “I never thought that she would die first,” he says. She was just 68. I said to him, “You took care of mom for ten years. That’s something few people could have done. How did you do it?” His answer: “Love!”

My dad, a very religious man, feels guilty about having placed her in a nursing home. He really had little choice, because she was falling frequently and had twice injured herself seriously – a broken wrist and a gash on the head that required surgical staples.

I think my mother declined so fast because, despite the breakdown of her cognitive abilities and her inability to speak, she knew she was no longer at home and no longer had the constant support of her spouse. Eating became increasingly difficult for her; that might have been her way of saying goodbye. I try to comfort my dad by reminding him that he took care of her very well for a long time and that he was no longer able to do so.

Bringing us closer

A week before the anniversary, my dad came into my home office sobbing. He immediately picked up the picture of him and my mom that I have sitting on a bookcase. He kissed my mother’s picture and then caressed it. “I do this every night before I go to bed,” he said. “I have the same picture of your mother at home. I pray for your mother every night. And I talk to her.”

I went over to my dad and hugged him. He seemed so small, frail, and vulnerable. This stoical man, a Depression kid who had never been close to his own immigrant father, had a similar distant relationship with me, but now he was reaching out for help. It had taken him many years to hug me when I was a young adult, and even then his hugs were always quick and tentative, ending in a little push away.

But on this night he held on for a long time and caressed my back, crying the whole time. It was the closest I had ever felt to him.

To encourage himself, my dad remembers that he still has me and my sister. “It was because of your mother that I have you,” he says. We are now his lifeline, his final hope.

On February 14, the start of our second year without my mother, I drove him and my daughter to a special place at the ocean that he and my mom had savored twenty years ago, a time when none of us had even heard of Huntington’s disease, let alone imagined the stress and tears it would bring for the whole family. We couldn’t visit my mother’s grave, so my daughter and I threw flowers over a cliff as a way of honoring her. As my dad and I remembered the good memories he and my mother had of this place, he became choked with emotion. Then for a good while we simply enjoyed watching my daughter play on the beach and become fascinated with a sand crab.

The future looms

After one of our meals last week, my dad saw me taking the supplements I hope will delay the onset of my own HD. He has known about my own positive test for HD ever since I had it done in 1999, but he seemed always to go into denial about it and showed no concern, perhaps because he had his own huge burden to carry in watching my mother succumb to HD.

On that night, however, he asked again why I was taking the supplements. I told him that I did not want to become like my mother. (I also reminded him that his granddaughter, 6, is HD-free because we had her tested in the womb.) For the first time he became upset, realizing that I too could die from HD.

HD, in its strange way, has brought my father and me together. Now my goal, as I do my small part along with other HD activists around the world, is to make sure that it never separates me from my own wife and daughter.