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.

Handling the news

Angela F., author of the blog A Survivor’s Guide to Huntington’s Disease?, learned on November 8 that she had tested positive for the genetic defect that causes Huntington’s disease. She asked me: “I am curious about how you coped when you got your results. How did you pull yourself back together to get on with life again?” Angela was especially upset – as I was – that her geneticist had told her she could do “nothing” to avoid the onset of HD.

I had to face the news of Huntington’s disease tests three times in just a little more than four years.

First, on the day after Christmas in 1995, I learned the explanation for my mother’s decline: a positive test for HD. (Ever since then, the holidays bring the stark reminder of how the threat of this disease has penetrated into every part of our lives and all of our discussions about the future.) The news came as a complete shock – especially because I learned that I had a 50-50 chance of inheriting HD.

Like many people, I had no knowledge of Huntington’s disease. I immediately called my mother’s geneticist back in my hometown to get more information.

Considering the news

I told him that I wanted to get tested immediately. But he cautioned me to take my time and to consider all of the consequences, including the danger of being denied insurance coverage. I contacted the head of the local chapter of the Huntington’s Disease Society of America (HDSA), a woman whose mother also had HD. She further counseled against a rash decision about the test. I began researching HD, especially the news of potential treatments, and I attended the next HDSA support group meeting, where I met other people at risk and, for the first time in my life, saw a group of individuals severely affected by the disease.

For the next three and a half years, I attended as many support group meetings as possible. I heard one scientist give a presentation on coenzyme Q-10, a supplement thought to be potentially effective against HD, and I started taking it. I listened to at-risk people tell of their wrenching decisions to test or not to test. I volunteered for the local chapter of HDSA, helping at fundraising events and dedicating increasing amounts of time to other activities.

This was my rational side in action. It was my way of fighting back and answering that inner voice that kept telling me, “You must do something!”

Emotions take over

However, as much as I unconsciously tried to cover them up, my emotions began to take over. A complex mixture of overwhelming fear and powerful denial regulated my life in the first few years after learning about HD.

On the one hand, I felt my life changing forever because of the possible onslaught of dementia and chorea, the shaking movements of HD. One night not long after the news about my mother, my wife and I lay in bed discussing HD. She held me tighter than ever before.

On the other hand, I became reckless in my pursuit of professional success and pleasure. Over a year, I took a big professional risk by focusing on a project that would bring me more immediate satisfaction and a shot at glory. That project kept me from confronting HD more seriously. I devoted very little time and effort to other parts of my life, including my relationship with my wife. My passion for life ran wild, but often in the wrong direction. Instead of solidifying what was most important in my life, I tried to escape into dreams of grandiosity. Because HD loomed as a specter in my life, I wanted to pack in as many experiences as I could before falling ill.

Throughout this period I put the question of testing for HD in the background. At the HDSA support group and from my readings, I learned that ignorance could be bliss. Living without the knowledge of my status was better than having to face the rest of my life knowing that I would die a long and horrible death caused by HD. I preferred not to play the 50-50 odds that I might have the genetic defect. After all, there was no cure or treatment for HD, so why suffer beforehand?

Facing the inevitable

I probably would have remained untested if it were not for the growing pressure from my wife to have a baby. Because of our careers we had not seriously talked of children in the early years of our marriage. But in 1998 and 1999, after the new stresses of my at-risk status had complicated our relationship and further caused us to delay having children, she gave me an ultimatum: have a child or end the marriage.

Agreeing to have a child was like a cold shower of reality. My at-risk status meant that our child could inherit HD from me. We absolutely wanted to avoid this, because we did not think we could withstand the pain of raising a child at risk for this horrible disease.

It was an especially gruesome possibility because of a particular twist in the genetics of HD: in the process of conception a man, unlike a woman, can pass on a worse version of the genetic defect to the child than he himself has.

Because of this, in some HD families the children actually get the disease much earlier than the age of onset of their fathers. My wife stated unequivocally that she did not want to care for both a husband and a child stricken with Huntington’s disease.

Wanting to conceive

We began to steel ourselves for the possibilities. One was preimplantation genetic diagnosis (PGD), a new procedure in which an embryo is tested for HD in a test tube and is then implanted in the womb. PGD would have allowed us to have a baby without HD and, if I wished, I could avoid knowing whether I actually had the defect.

However, to obtain PGD we would have had to spend many weeks in distant Washington, D.C. and far more money than we could afford: $100,000. (PGD has since dropped to about one-tenth of that cost and is now available in other parts of the country.) PGD was out of the question, and there was no guarantee the embryo would develop successfully.

Another option involved testing the fetus in the womb. If the baby did not have HD, I could still continue with the ignorance of my own status. However, if it did have HD, I would know for sure that I too would get the disease.

The third option was logistically the simplest and cheapest, but emotionally the hardest: I could get the test before we checked the fetus. If I tested negative, we could forget about Huntington’s ever affecting our own family. However, if I tested positive, we would immediately have to deal with my results and prepare to test the fetus in the womb.

A tough choice

I decided on the third option. I was 39 and felt life passing quickly, and if I were ever to become a father, it would be then and with my wife. I also tapped into a reserve of bravery and stoicism that I inherited from my father. (He ultimately cared for my mother every day for more than ten years before she died on February 13 of this year.) And so I began preparing for the news of a second Huntington’s disease test.

It was the spring of 1999. A sense of calm and resoluteness overtook me. Most people go through counseling and a specific protocol for getting tested, but I skipped parts of this process. I had my own very effective therapist and, with my experience at the HDSA chapter support group, was already familiar with the issues involved in testing.

We also had a very intelligent, level-headed, experienced, and compassionate geneticist who carefully explained all of the details of the testing process and patiently answered all of our questions. Looking back on it, I think I handled quite well the weeks preceding my test results.

Gathering for the results

The day of the results began like any other, but as we approached the hour its momentousness weighed like a millstone around our necks. My wife, who was my official support person, and I drove to the office where we were to receive the results. We tried to keep an upbeat attitude until the very last minute. She and I sat together on one side of the table, holding hands on the table, while the geneticist and a counselor sat on the other side. My wife was convinced that I would test negative. One of my best friends thought so too. We were looking forward to a celebration and getting on with our lives.

The geneticist this day was very businesslike, objective, and maybe even detached. His job could be very unpleasant, this revealing of a person’s future in few sentences, as if he were reading someone’s palm or tarot cards. He needed to be professional and to maintain a respectful distance. He stated that we were gathered to receive the results of my test. Without pause he began to read the results rather quickly and without hint as to what the results would be.

In Huntington’s disease everything hinges on the number of CAG repeats that a person has on the gene called huntingtin. (CAG repeats refer to the sequence of three nucleotide bases – cytosine, adenine, and guanine, building blocks of DNA – on the DNA molecule.) Everybody has this gene, but it usually has only 20 or fewer CAG repeats. My mother had twice as many, and that is what caused her to start having symptoms of HD in her late forties.

When the geneticist read the results for the first allele (an alternate form of a gene, for example, alleles for eye color, hair color, etc.), which came from my father, it was in the normal range. I gained a great sense of expectation, and I could sense that my wife was beginning to let out a sigh of relief.

All we needed to hear was the number “20” one more time.

The reading for the second allele, which came from my mother, was …

…

40.

Everything changes

40. It is a number stamped in our memories and in every cell of my body, slowly but surely wreaking havoc in my brain cells and leading to the moment when I will become like my mother.

40. It’s part of the primer we give to people unfamiliar with HD.

40. It’s like a code for everything my wife and I have discussed and suffered over the past eleven years of dealing with HD.

40. Would the child we wanted also have to live with this number, or, because I was a man, an even higher one?

40. I was almost at that age, the prime of a typical adulthood, but mine was not to be that.

After hearing the results, we were speechless and suddenly drained of energy. It reminds me of the day my childhood best friend died in a car accident just days before his high school graduation. I collapsed in a chair and cried.

On that day in 1999, we were clearly shaken. I am a very careful driver, but as I pulled our new car out of the space in the parking garage, I unintentionally scraped the right front fender against a column. My wife became scared. We had just learned that I could die of a debilitating brain disease, and here, out of fear and anxiety, I was already acting erratically.

But we did not cry. We remained determined to move ahead with our lives and our plans to start a family.

Moving forward

The geneticist had helped a lot by leaving us with words he would repeat on other occasions: “a positive test is not a diagnosis for the disease.” I was gene-positive, but I did not yet have any noticeable symptoms. That phrase has often given me hope in moments of fear.

For the next few weeks we solemnly went on with our lives. Like a shaman trying to preserve the life of a patient, my wife filmed me as I spoke about the test results, my fears, and my hopes for the future.

My positive result required us to think about a third HD test. My wife was already pregnant, so we began to make plans for testing the fetus in the womb. In July, however, she had a miscarriage. It was a devastating experience, especially for her, but I have always looked back on it as possibly a fortunate one, because I suspect that baby was positive for HD.

By October of 1999 my wife was pregnant again. We met with the geneticist once again to map out a strategy for testing the fetus.

It was a very complex affair. For fear of losing health coverage in the future or jeopardizing the purchase of other types of insurance, we had not mentioned HD to representatives of my health plan.

A tragic irony

This is one of the great and tragic ironies of living at risk for a devastating brain disease. The insurance one pays for often cannot be used because of the deep fear and very real possibility of suffering discrimination.

Our geneticist worked with the local Huntington’s disease clinic but not our health plan. My HD test was done anonymously at that clinic. But the HD clinic could not conduct the amniocentesis necessary for drawing the genetic material to be used for testing our baby for HD. Luckily, two things worked in our favor. The geneticist had a contact at the health plan, and that person arranged for my wife to have a standard amniocentesis done to check for Down’s syndrome. The lab that tested for this happened to be the same lab where the geneticist worked and tested genetic material for HD, so when the sample came over for Down’s syndrome screening, the geneticist also prepared to test it for HD. The health plan would get the Down’s syndrome results, which were negative, but only we and the geneticist would learn the results of the HD test.

Working around the health bureaucracy was a harrowing experience, but nearly as much as what we now faced. My wife was already sixteen weeks into the pregnancy when the amniocentesis was performed. The HD test, however, would take place only several weeks later, after the lab had been able to grow the genetic material sufficiently so that a reading for Huntington’s disease could be obtained. The results would come when the pregnancy was already nearing the fifth month.

Facing abortion

And what would we do if our little daughter-to-be were positive?

My wife and I had started debating this question even before I received my test results. During the pregnancy it paralyzed her emotionally, because she could not fully commit to a baby whom we might abort because of a positive test for HD. Every night as I put my hand on my wife’s stomach and talked with her about the new life growing inside of her, a wave of fear and uncertainty overtook us.

We are both Catholic and do not like abortion, but we also believe in a family’s right to choose. My wife insisted again that she did not want to take care of two HD patients. If the baby tested positive, she wanted to have an abortion. I understood her concerns but wanted us to await the results first.

My result of 40 CAG repeats once again impinged on our lives. I argued that if the baby had 40 repeats like me, we should go ahead with the pregnancy. Why should we deny life to a child who would probably live as long as I had, then 39, without symptoms? Surely, I argued, treatments or even a cure would be found by the time she grew up.

But my 40 could become our daughter’s 41 or more. With each additional repeat, the likelihood of an earlier onset and a harsher version of the disease increased. For weeks we debated what number would become our maximum tolerance of risk. I would accept anything in the low forties, which was the likely outcome. But my wife kept worrying about the doubt that would exist about our daughter’s health.

The horrifying thoughts of the abortion itself traumatized us more than anything else. The middle of the second trimester was awfully close to viability. My wife would have to undergo an operation and spend at least one night in the hospital. We knew this experience would scar us for the rest of our lives, and maybe for eternity.

Living with uncertainty

We continued our lives as best we could, but HD once again dampened our holiday spirit. Each night my wife and I held hands in bed, and I kept my other hand over her growing belly. Very soon we expected the baby to start kicking.

To get my results we had traveled to the HD clinic. This time we wanted to be alone at home, so the geneticist agreed to call us on the phone with the results.

He called on the evening of January 28, 2000. I got on the phone in one room, and my wife got on the extension in the other room. This time I noticed his voice was more upbeat, offering a sense of anticipation.

“Your child has tested negative,” he said.

I thanked him more enthusiastically then I had ever thanked anybody before.

It is no wonder that each year we send him a family Christmas card.

As soon as we got off the phone, my wife and I fell into each other’s arms on the couch and cried with relief. Aside from the day of our daughter’s birth, it was the happiest moment of our lives.

She became our “miracle baby.” I would someday fall victim to HD, but she would not, forever wiping HD’s horrible legacy from our family tree. Now each day, as I watch her grow, I delight in my daughter. If I ever think about her and HD in the same context, it is not about her suffering, but about her seeing me become like her grandma.

Maintaining a positive attitude

To answer Angela F.’s question, there’s a lot we have done to pull our lives back together after Huntington’s disease entered the picture, and the stories I’ve related are just a part of it.

It is not true that there is nothing to be done. Every moment is a challenge. Big decisions are frequent. Along the way we have taken control over our lives as much as possible. HD is there, but at least we know our enemy and can try to fight it through activism, research, and maintaining a positive attitude.

Mourning mom

It has been almost nine months since I’ve written in this blog. Last March I began to write the following:

My mother died in her sleep on February 13.

So ended 15 years of struggle with Huntington’s disease.

I still cannot believe that she is dead.

But in many ways she had already died long before February 13. The dementia of HD had slowly but inexorably done away with her ability to communicate and to lead a normal life.

Seeing her in the casket at the funeral home, I could not cry. She seemed to still be with us. Only after the wake, when the time neared for the lid to be closed, did I finally break down.

In some ways my mother’s death was a relief. HD had dehumanized her. That’s why we had decided against connecting her stomach to a feeding tube. Her suffering has ended. Indeed, in death she had a look of peace on her face.

I am tired of thinking of Huntington’s disease, this threat from my genes that taunts me every day but has yet to manifest itself.

Now that Mom is gone, I am preparing myself to renew my energies for the continuing battle to find a cure.

After I wrote that – which I did not post to this site – I could not bring myself to write again. Starting around that time, and extending into May, I went into a dual spiral of anxiety and depression.

I also went into denial about my mother’s death and Huntington’s disease, especially because I had traveled home to see her just a couple weeks before her death. At the nursing home I squirmed with fear as I looked into the genetic mirror that revealed the symptoms and decay that I myself likely will experience in the not-too-distant future, because I too have tested positive for HD.

I badly needed a break from HD, and staying away from this blog has been part of that process.

Without realizing it, I began to take on the symptoms of an HD person. The littlest of tasks became like mountains to climb, and thinking about bigger responsibilities and plans terrified me. Whenever I became anxious, I started to rock back and forth on my feet or bow my head ever more quickly and ever closer to the floor. My hands fidgeted too. My wife had to keep telling me to get a hold of myself. I simply didn’t know how I was going to get through the next minute, let alone the next day, week, or month. I couldn’t enjoy anything. I rocked back and forth even when playing with my daughter, although I tried to do it only when she wasn’t looking.

I was acting out my feelings of doom. Seeing my mother in such a horrible state before her death drove home more than ever the utter destruction wrought by the disease and the inevitability of its arrival in my own body. On a deep level I was convinced that I would get this disease.

On another level I was identifying with my mother by taking on her suffering. This was my way of being close to her in death. I was her son, I had inherited her gene-positive status, and now I would be just like her.

I also felt guilty about her death. Why had I not visited her more often? Why did I often ignore her when I was in the same room with her? Could I have done more to save her? I began to ask myself these questions in the months following her death and realized that avoiding her was a way of repressing my own fears about the disease. Maybe I deserved to get HD.

And I was struggling to come to terms with death itself – not death as most people think of it, but death in one of the most excruciatingly painful ways imaginable, dragged out over many years and pronounced to oneself and to everybody else as the HD-stricken adult disintegrates into a creature more helpless than a toddler, incontinent, unable to swallow, speechless.

I don’t know how I got to the month of June without totally breaking down. Luckily, I got on some new medications for anxiety and depression. They helped enormously, and now I feel better than I have felt in years.

Denial has helped, as well. For many months after my crisis I have simply blocked out of my mind the possibility that I am gene-positive for HD. I stopped fantasizing about symptoms. I stopped worrying about when I would get sick. I tried to live in the moment as best I could.

I also started taking time out to enjoy life. In July we splurged and went on a week-long family cruise to Alaska. Seeing whales, eagles, green mountains, fjords, and glaciers calmed me and renewed my spirits. Being at one with nature made my worries and the death of my mother seem less ominous. Lately I have been thinking that my fate with HD is just another act of nature, part of the grand mystery of God and the universe.

Above all the trip was important because my dad came with us. He was crying every day about my mom. He wondered what he was going to do with his life, and he talked about how he would soon join her. Even though HD had destroyed her mind, she had been his companion. As he kept reminding me, 48 years with a person was a very long time. He’s 79.

The trip got his mind off of mom and focused on the living members of his family, especially his granddaughter. At six, she now has an understanding relationship with her grandfather. When my wife asked her if she wanted to see grandma in the casket, my daughter said yes. She stared for a long time. It was the first time she saw a dead person. She attended the funeral, laid a flower on the casket at the cemetery, and witnessed the pain of all of us. She clearly made the connection between Huntington’s disease and death. At our home and on the cruise ship she saw her grandfather without his spouse. She held his hand and in her own special way helped draw him out of himself and his suffering.

It was also a time for my father and me to bond again. We shared a room for the first time in more than twenty years. He watched me take supplements that I hope will delay the onset of HD. After so many years of focusing on my mother, for the first time he has realized that this disease can affect me too.

As fall sets in and the first holiday season without my mom approaches, we are back at the routine of life. My daughter is in first grade, and my wife and I are in full swing at work. My dad visits his doctors, goes to weekly Mass, helps the neighbors, and feeds the squirrels and birds that appear in his yard.

And we are all girding ourselves for the next battle with HD: a father wondering whether his son will follow in the footsteps of his spouse, a wife worrying about raising a child and caring at the same time for a sick husband, a daughter reassuring herself that all will be okay with her parents.

And I, taking many months to get up the courage to write again, am finally coming to grips with the death of my mother at the hands of Huntington’s disease.