Designing the best drug possible to defeat Huntington’s disease

With an eye on starting a clinical trial possibly as early as 2014, a scientific team in San Diego is painstakingly working to design the best drug possible to defeat Huntington’s disease.

For the past seven years, Don Cleveland, Ph.D., of the Ludwig Institute for Cancer Research at the University of California San Diego (UCSD) and Frank Bennett, Ph.D., the senior vice president for research at Isis Pharmaceuticals, Inc., have envisioned treating HD with a revolutionary gene-silencing technology that, if successful, would attack the disease at its genetic roots and perhaps even partially reverse symptoms.

Since late 2007, the UCSD and Isis teams have partnered with the CHDI Foundation, Inc., the multi-million-dollar non-profit biomedical organization dedicated to finding HD treatments. Together they aim to develop what Dr. Bennett has described as a “laser-guided missile” to prevent the damage to brain cells caused by the mutant huntingtin gene carried by HD patients.

Dr. Cleveland and Isis senior scientist Holly Kordasiewicz, Ph.D., were honored as the 2012 Researchers of the Year by the San Diego Chapter of the Huntington’s Disease Society of America (HDSA-San Diego) last night before some 500 attendees at the chapter’s twelfth annual Celebration of Hope Gala.

Isis employs a cutting-edge technology known as antisense oligonucleotides, or ASOs. DNA, the building block of life, runs our cells by telling them which proteins to make. It does so by sending messages with another molecule called messenger RNA.

As encoded by DNA, RNA has a very specific template, somewhat akin to a unique electrical outlet into which a plug can fit. RNA is known as a sense molecule, and Isis manufactures specific ASOs, artificial strands of DNA, to act as antisense molecules, the plugs that control the RNA. (Click here and here to read previous reports on the project.)

The ASOs accomplish two goals. First, they destroy the huntingtin RNA and thus prevent the production of the huntingtin protein. Second, eliminating the RNA removes it as a potential cause of other problems in the cell.

Above, some of the Isis HD team members: (left to right) Michael Oestergaard, Punit Seth, Bethany Fitzsimmons, Curt Mazur, Amy Blackley, Eric Swayze, Holly Kordasiewicz, Frank Bennett, and Marco Giorgetti (photo by Gene Veritas) (click on image to enlarge). Below, Gene Veritas inside the Isis facility in Carlsbad, CA (photo by Amy Blackley, Isis).

  

Fine-tuning, tailoring, and twiddling

Isis had originally hoped to begin a clinical trial as early as late 2010, but has delayed the project in order to perform highly important fine-tuning on several fronts.

As previously described by Dr. Bennett, Isis is searching among the many “flavors” of ASOs it makes in order to find the best match for treating HD. From an original pool of thousands, Isis has narrowed down the candidate ASOs to just five, Bennett said in a recent interview.

Isis, CHDI, and other researchers have also made significant advances on two other key research questions. First, how much of the huntingtin protein should the drug remove? So far, the scientific consensus seems to have settled on 50 percent lowering (also known as  knock-down) as the current target. However, this question will ultimately be resolved through the clinical trials.

The second, related question is trickier but could ultimately open the door to an even better drug. Because HD patients have both mutant and normal huntingtin proteins in their brain cells, should the drug lower both or just the mutant? In the early going, the ASOs did not distinguish between the “good” and “bad” proteins. However, Isis has now developed a way to knock down just the bad.

At least in theory, knock-down of just the bad is the safer approach for patients, although the project’s experiments have also surprisingly demonstrated that knock-down of both is not harmful, explained Dr. Kordasiewicz, the former head of the HD project in Dr. Cleveland’s UCSD lab.

Dr. Holly Kordasiewicz in the lab at Isis (photo by Curt Mazur of Isis)

“The decision still hasn’t been made,” she said, referring to the choice between the two types of ASOs. “It’s hedging your bets. Everything’s on the table. The chemists are doing amazing things. It would be irresponsible of us not to consider all of the options before making our final decision.”

“You never know, once you get into a human, what’s going to work,” she added. “So having everything ready to go, so you don’t have to wait three more years to develop the next thing, if one doesn’t work, you try the next.”

Using second-generation ASO technology, the Isis chemists found ways to increase both the selectivity (the ability to bind to the mutant RNA as opposed to the normal one) and the potency of the potential HD drug.

“It improves potency quite a bit,” said Punit Seth, an Isis senior research fellow in medicinal chemistry, in describing one of the key chemical innovations. “You can get anywhere from three-fold to ten-fold improvement, which then translates to lower costs in drugs and administering less [of the] drug to the patients.”

Dr. Cleveland added that these improvements would also produce a drug with potentially fewer side effects.

Eric Swayze, Ph.D., Isis’s vice president for medicinal chemistry, summed up the fine-tuning as “tailoring” and “twiddling with the number of different building blocks” that go into the ASO.

“It turns out to make a huge difference, which we didn’t really expect,” he observed.

Dr. Eric Swayze explains the function of the Isis ASOs (photo by Gene Veritas).

Patient-friendly delivery

Isis has also strived to simplify the delivery of the drug. Originally, the company planned to direct the drug into the brain using a device implanted in the abdomen and connected to a catheter running under the skin to the skull.

Now, however, the researchers aim to introduce the ASO directly into the cerebral spinal fluid (CSF, the fluid that bathes the brain) by injecting it through a quarter-sized port implanted near the rib cage, with the catheter running to the area of the spinal cord.

This method is “more convenient to the patient and longer-term more commercially attractive,” Dr. Bennett observed.

Gene Veritas (left) with Dr. Bennett at a CHDI conference in February

Dr. Bennett noted that Isis gained valuable experience in drug delivery through a trial of its ASO drug for spinal-muscular atrophy, a childhood neurological disease. Isis also has conducted a Phase I ASO clinical trial for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.

With the improved delivery method, instead of continuous infusion of the drug, patients will probably need only occasional injections, each one lasting only a few minutes, Dr. Bennett added.

“There’s a long history of safety and efficacy using this method,” he said.

Furthermore, the Isis approach avoids the potentially more risky delivery methods used in two other HD gene-silencing approaches: the use of a virus, or an operation on the skull to introduce the drugs into the brain.

Getting into the brain

To improve the efficacy and safety of the ASOs, Isis and CHDI have been testing them in mice and non-human primates.

One of the key mouse testing sites is Dr. Cleveland’s lab at UCSD, where an HD team led first by Dr. Kordasiewicz and, after her departure to Isis, by Clotilde Lagier-Tourenne, M.D., Ph.D.

In conjunction with experiments in other labs, the Cleveland HD team has demonstrated surprisingly good results.

One major hurdle to treating the brain is the blood-brain barrier, which shields the brain from foreign substances that might cause harm. The barrier makes it difficult to get drugs into the brain.

Significantly, an article recently published in the journal Neuron, with Dr. Kordasiewicz as the lead author, suggested that the ASOs delivered via the CSF reach a wide area of the non-human primate brains, including the regions known as the cortex and the striatum, two areas critically damaged in HD.

As Dr. Cleveland explained, a decade ago scientists viewed neurological diseases as the result of problems in a particular kind of neuron (brain cell). Since then, they have developed a radically different view: the various kinds of cells are linked together in a system – including connections between the cortex and the striatum.

“It’s actually a disease not just of individual neurons but of the whole system, a neuron and the cells surrounding it,” Dr. Cleveland said of HD. “It’s such a simple message. It’s a little surprising that it took so long to realize it. Neurons don’t live by themselves. They require their partners, and the partners develop damage that drives and spreads disease. So, in Huntington’s disease it’s now clear that there’s a partnership between striatal neurons that send projections into the cortex and vice versa.”

Above, Dr. Cleveland in his office at the Ludwig Institute for Cancer Research on the UCSD campus. Below, Dr. Cleveland with lab scientists Jon Artates (middle) and Jihane Boubaker (photos by Gene Veritas).

A ‘Huntington’s holiday’

The most stunning test results involved the amelioration of symptoms.

“Because we are hitting the cortex to such a high level, my prediction would be that we will have a very strong effect on things like cognition and mood and anxiety,” said Dr. Kordasiewicz of the ASOs’ ability to restore brain functions lost in HD. Chorea, the shaking and trembling that occurs in HD, also could be ameliorated, she added.

By reducing the level of mutant huntingtin protein in the mouse brains, the ASOs reversed the HD-like symptoms.

“It was better than we could have imagined. In the sickest animals, we stopped further brain loss,” said Dr. Cleveland “In other mice, a single treatment led to partial reversal of symptoms. And what’s more, the improvements lasted more than six months after a single treatment. And even then, the disease process did not start back up. It was amazing.”

Dr. Cleveland observed that, unlike other kinds of substances the ASOs are made of DNA that isn’t rapidly degraded by enzymes the way many other drugs are affected.

“Once they get intracellular, they’re intracellular acting to catalyze the destruction of the target RNA for, not just hours, not just days, not just weeks, but actually months,” he continued. Just a single injection of the ASO leads to a month of huntingtin RNA suppression in mice. A two-week infusion brings four months of suppression.

The scientists refer to the as yet unexplained symptom-free period after the ASO treatment is gone as a “Huntington’s holiday.”

Dr. Cleveland speculated that “since it takes 30-40 years for HD symptoms to develop. If you could introduce a Huntington’s holiday, maybe you could reset the pathogenic process so that it might take a considerable time to build back up.”

As he and others have observed, success with this approach means people might need to take an ASO HD drug only a few times per year.

As a preventive remedy, a future generation of ASOs might even be prescribed early in life for individuals like me who have tested positive for HD but remain asymptomatic, Dr. Cleveland added.

Watch Drs. Cleveland and Kordasiewicz receive their HDSA-San Diego awards and speak about the promise of their work for an HD treatment in the video below.

HDSA-San Diego 2012 Researchers of Year from Gene Veritas on Vimeo.

Measuring the impact in people

In the final run-up to the proposed clinical trial, the Isis-UCSD-CHDI team and its collaborators are seeking the answer to two more crucial questions: how can the efficacy of the ASO be measured when humans participate in trials? And what is the proper size and frequency of the dose?

The impact of the ASOs on mice and non-human primate brains is fairly easily measured. However, the scenario is different for humans, who cannot be manipulated, sampled, or subjected to the other kinds of experiments done with animal models.

To answer these questions, the scientists are seeking to develop “biomarkers” for the ASO effects.

As Dr. Cleveland explained, the researchers are hoping to find “signatures” in the cerebral spinal fluid of the trial participants that would indicate the impact of the ASO. Those signatures could be related to both to alterations in genes and the secretion of proteins.

“It’s a very big experiment,” Dr. Cleveland said. “We need a partner like CHDI with deep pockets to do this. It’s an expensive experiment, but we absolutely have to do it. Can we find biomarkers? I’m an optimist. We’ll know the answer over the next six months.”

If successful, this experiment will help the scientists determine the amount of drug to give to the patients and provide specific measures of drug impact.

The pharmaceutical firm Novartis has found a way to measure the huntingtin protein in the bloodstream and is seeking to do so in the CSF. The Isis-UCSD-CHDI project also has at its disposal the valuable data from long-term natural history studies of HD patients (TRACK-HD), and it will also probably rely on brain imaging of the trial participants.

Light in the tunnel

In 2013, Isis hopes to select the final ASO drug candidate to move into pre-clinical testing. If that testing is successful, then the company will need another 12-18 months to obtain approval from the Food and Drug Administration to initiate the Phase I human trial.

Planning for Phase I will involve not only the ASO researchers, but toxicologists (who check for safety), pharmacokineticists (who measure the penetration and exit of the drug), and clinicians (who work with and care for the trial participants).

“They’re already starting to engage in the project, because they can see the light at the end of the tunnel,” said Dr. Bennett. “They’re becoming involved in thinking through the strategy of how we’re going to develop this drug.”

Dr. Bennett emphasized that Phase I effort’s main purpose is to measure safety and tolerability – not drug efficacy – although the researchers will also take note of the effects. If Phase I is successful, efficacy comes into play in the potential Phase II and III trials.

“We’re committed to try to do our best to bring that drug forward,” said Dr. Bennett, who noted that the Isis HD team has worked many nights and weekends to speed the project. “There’s still a lot of caveats in there. The best-laid plans sometimes run into roadblocks. But we are very enthusiastic. We’re in this to help patients.”

“For patients and their families, I know it’s too slow, but I don’t think it could be done any faster,” concluded Dr. Cleveland. “I think everyone’s working absolutely flat out.”

Bringing hope to the HD community: Dr. Cleveland at the Gala with advocate Amy Anderson, wife of Craig Anderson, a former pilot afflicted with HD (photo by Gene Veritas) 

Playing in the fourth quarter of life as Huntington’s disease looms

Seeing my mother succumb to Huntington’s disease at the age of 68 and living in fear of the onset of my own symptoms, I have come to appreciate the preciousness of time.

One of my closest HD confidantes and I frequently measure time in terms of the four quarters of a football game. We see most people like us, in our early fifties, as playing somewhere in the third quarter, the prime of life.

However, I’m well into the fourth quarter. I’ve already reached my mother’s age of HD onset, and I will be extremely lucky to reach 60 without a serious reduction in my brain power and the start of chorea, the shaking and trembling experienced by most HD patients. Indeed, I cannot imagine life beyond 60, a time when my only child will be in college. I’m deeply saddened that, in an era when more people than ever are working into their late seventies and even eighties, I may have to stop in just a few years.

Because HD is inevitable, I know the symptoms will start, even as I hold out hope for some scientific breakthroughs. Maybe I’ll get a “mild” case – or maybe I’ll suffer just as badly as my mom. Like hers, most cases of HD I know devastate people physically, behaviorally, and cognitively, leaving them mere shadows of themselves.

So, these days I’m throwing long passes, aiming for touchdowns.

I’m also starting to focus on putting my affairs in order to facilitate matters for myself, as well as my wife and daughter, if HD becomes so bad that I can no longer work or take care of myself.

It’s time to prioritize. That includes stepping back a bit from this blog. Regular readers will notice that recently I’ve written much less. After a period of intense writing, I need to replenish my emotional energy.

And, in perhaps the most important process of all, I’m learning to accept my defeats, the disease, and, ultimately, my mortality.

Throwing long in the publishing world

As an activist for the Huntington’s Disease Society of America (HDSA), I’ve strived to help build awareness, although my need to remain anonymous and avoid genetic discrimination has, until recently, stymied that goal in terms of reaching out personally to people.

In mid-2010 I started to exit the terrible and lonely “HD closet” by making speeches about my family’s struggles with HD. Since then, I’ve made some ten presentations, most recently at the HDSA annual convention.

As a writer, I decided to attempt some long passes in the hope of generating greater media exposure about HD and the need to research and treat neurological disorders.

This is my moment.

Towards my goal, I’m working to publish a book about my family’s experiences with Huntington’s and scientists’ and drug firms’ quest for effective treatments. I hope to add to the excellent writings of other HD authors, including Jim Calhoun, Trish Dainton, Susan Lawrence, Carmen Leal-Pock, Sandy Sulaiman, and Alice Wexler.

How to ‘sell disease’

In today’s world, publishing a book on HD is an especially daunting challenge. With the rapid decline of traditional bookstores and the rise of the e-book, publishing is undergoing a revolution. It’s also become a virtual monopoly of an elite of blockbuster authors.

One clear message is that “disease doesn’t sell.”

Furthermore, so-called orphan diseases such as HD – with an estimated 30,000 affected people and some 250,000 at-risk – are orphans not only for the drug industry, but for the media.

Despite the terrible drama of conditions such as HD, in this information-saturated age it’s hard for people to grasp a disease that doesn’t directly affect them or loved ones.

However, in June came the encouraging news that former Palm Beach Post reporter SusanSpencer-Wendel signed a book contract for $2.3 million to chronicle how she will fulfill her “bucket list” of desires as she struggles against Lou Gehrig’s disease – a condition with approximately the same number as affected individuals as HD. She also received a seven-figure movie deal.

Indeed, disease can sell – if one has good media connections like Spencer-Wendel and discovers a way to link a story to trendy themes.

As a gene-positive HD person and HD activist, I believe disease should sell. The imminent tsunami of people affected by neurological disorders will add enormous stress on caregiving communities and the healthcare system.

Not in my wildest imagination have I thought a publisher would pay millions for a book about HD, but I do hope that, by earning at least a modest fraction of that, I could help insulate my family from financial crisis in the event of my illness and make a substantial donation to HDSA.

Focusing on the basics

As I’ve reflected on my goals, I’ve also come to recognize the danger of my ego taking my focus away from what matters most.

“Vanity of vanities!” the biblical Book of Ecclesiastes tells us. “All is vanity.”

I will continue to write about HD and strive to publish a book. However, as I head deep into the fourth quarter, other goals take on increased importance.

“Forget about the glamor,” I told myself. “Get to the basics.”

Later I quipped to myself: “God doesn’t read resumes!”

For 10 days in June, I got away from the worries of writing, career, and Huntington’s disease by traveling with my family to restful spots in northern California.

After visiting the La Brea Tar Pits in Los Angeles, we spent several days hiking in Yosemite National Park. We traversed the expansive and hot Central Valley, drove down the Avenue of the Giants in one of the state’s virgin redwood forests, strolled along the idyllic shoreline of Crescent City, took in the wild coast of Mendocino County, and celebrated our HD-free daughter’s twelfth birthday in San Francisco.

Enjoying these natural and human treasures together gave us a deeper appreciation of our home state. It also strengthened our family bonds and deepened my commitment to my daughter as she prepares to embark on a new adventure at a private school just as she enters adolescence.

At Glacier Point in Yosemite National Park

On the dock at Crescent City

Confronting the hard reality

In the HD movement we all need to strive for the big successes – such as big fundraisers, media attention, advocacy for stem-cellresearch, improved Social Security legislation, and other pressing needs.

But, as our community knows so tragically, both individuals and families need to prepare for the hard, scary reality of HD.

Instead of writing, this summer I’ve focused on dealing with the inevitable onset of symptoms – and my eventual death.

Already in January, as I prepared for the potential fallout of going more public through my writing, I had participated in an HDSA webinar on genetic discrimination. On July 11, I took part in another webinar titled “preparing for the unknown,” which discussed the importance of establishing end-of-life directives for caregivers and loved ones. On August 8, after my annual appointment for cognitive testing at the HDSA Center of Excellence for Family Services and Research, I picked up a copy of a sample advanced directive.

This summer I also reviewed the slides from a March webinar on “workplace accommodations for HD” – an especially crucial topic for me because I plan to continue as long as possible in my position as a university professor.

Receiving this information has helped me start to prepare mentally, emotionally, and logistically for the onset of HD

Putting things in order

In recent months I’ve fantasized a lot about retirement – from both my career and the HD movement.

“Our culture thinks it’s cool to be exhausted,” I wrote recently in my notes about this fantasy. “We wear it as some kind of badge of honor. I myself have been like this. But it’s absolutely nuts! I need to pace myself, keep getting down time. It’s so true what I’ve heard in Brazil: Americans live to work, Brazilians work to live.”

In particular, this summer I’ve also felt a powerful urge to put my life in order, especially those areas I’ve long neglected because of time spent on HD activism. In the fourth quarter, it’s time to take stock of my life – and to enjoy doing so.

I began by transferring the songs from several hundred music CDs onto iTunes. Listening to many of these songs for the first time in decades brought a flow of good memories from my twenties and thirties.

Next, I reorganized my home office for the first time since we moved to this home in September 1999. I threw away garbage bags laden with hundreds of old 3.5-inch diskettes, checks and check registers going back to the early 1990s, and numerous other unneeded items.

I like the idea of traveling lighter on my journey with HD and through life.

I finally caught up on our home movie collection, started scanning old family photos that are beginning to fade, and filed work and HD-related CDs and DVDs in a storage case I had bought about four years ago.

I like caring for plants. I potted three new ones and placed them by the window. It felt great to get my hands dirty and to smell the soil. Sunday evening is watering time.

What causes this desire for order? The natural rhythm of life? A side effect of HD’s subtle psychiatric symptoms, which can include obsessive-compulsive behavior? Just plain fear of onset?

Whatever the cause, the greater sense of order has brought me a sense of comfort, of preparedness for HD and whatever else life might bring, of living the moment.

Shifting passions, accepting fate

I’m in a fight for my life against HD. Ironically, that means that perhaps it’s time to stop fighting so hard. Fighting too hard can worsen stress. A positive family life, exercise, tranquility – these are the real keys to personal survival.

I have a stable job, a loving family – and the tremendous gift of so far having avoided HD’s classic symptoms.

Tranquility and stability will help me negotiate the dramatic shift in my professional career from an emphasis on Latin American history to the history of science and the chronicling of the HD movement.

In one of my recent dreams, I plunged down a Rio de Janeiro hillside on the back of a wheelchair driven by a disabled man – undoubtedly an HD man – who, like my mother, could not speak.

I used to value traveling to Brazil. Savoring those experiences brings a warm glow to my heart. As a professor and father, I pass on those experiences to the next generation.

Now I’m becoming excited about new kinds of travel: through the biotechnological revolution, through my own mind in search of its meaning.

Yet, despite the vast progress in brain research of recent decades, the drug industry still has not produced a single remedy for neurological disorders. Although I never abandon hope, I also understand that a treatment may not arrive in time to save me.

Ultimately, tranquility and stability will help me prepare spiritually for the onset of HD: the realization that, in the end, I must accept my fate.

From a paralyzed genius, lessons of determination and caregiving for the Huntington’s community

In my fight to avoid the onset of Huntington’s disease, I have sought inspiration in model lifestyles, outlooks, and individuals.

One of my heroes is Stephen Hawking, the theoretical physicist who pioneered the science of black holes, Hawking radiation, the origins of the universe, and the quest for a “theory of everything,” an explanation of the ultimate forces and laws that govern the universe.

Hawking achieved all of this while surviving five decades with ALS, amyotrophic lateral sclerosis, known in the U.S. as Lou Gehrig’s disease and in Hawking’s native England as motor neuron disease. As is well known, ALS has completely paralyzed Hawking’s voluntary muscles, relegating him to existence in a motorized wheelchair with an on-board computer through which he speaks.

Hawking at the White House with President Barack Obama in 2009 (photo from www.hawking.org.uk)

When doctors diagnosed Hawking with ALS in his early 20s, they gave him two years to live. However, through sheer determination and with the support of his devoted wives and numerous friends and nurses, Hawking not only survived but achieved remarkable accomplishments. On January 8 he celebrated his 70th birthday.

Like millions around the globe, I am awed by Hawking’s brilliance, moved by his triumph over ALS, and cheered by his good humor and kindness.

I have just finished Stephen Hawking: An Unfettered Mind, a new biography by Kitty Ferguson.

It richly details Hawking’s extensive achievements in physics and his views of the origins of the universe, including the question of God. Reading about Hawking and his ideas, I feel the enormousness of the universe and, as he does with ALS, put the disease that claimed my mother, and that I face, in a healthy perspective.

An Unfettered Mind also portrays Hawking’s struggles with ALS, his utter dependence on caregivers for survival, and his and his first wife Jane’s fight to improve life for the disabled.

For HD activists, I believe that Hawking’s life offers valuable lessons to help strengthen our resolve to fight and demand better care for HD patients.

The ravages of ALS

Whereas HD is a fully genetic disease, only about ten percent of ALS cases are inherited. Researchers do not know the cause of the other 90 percent.

Like HD, ALS is debilitating and deadly. As Ferguson points out, ALS causes disintegration of the nerve cells in the spine and brain that regulate voluntary muscle activity. The muscles controlled by these nerve cells atrophy. Eventually every voluntary muscle in the body becomes compromised, making movement of any kind impossible. After diagnosis, most ALS patients live only a few years, dying from pneumonia or suffocation.

Patients experience no pain, and, unlike with HD, remain lucid to the very end. As Ferguson explains, patients in the final stage are prescribed morphine for panic and depression.

Hawking’s symptoms began as clumsiness during his third year as an undergraduate at the University of Oxford. Upon starting graduate studies at the University of Cambridge, he had difficulty tying his shoes, and his speech started becoming slurred.

Hawking experienced frequent fits of choking. In the summer of 1966 his fingers started to curl; writing by hand became almost impossible. A few years later he started using crutches. It took him 15 minutes just to climb the stairs at home. By 1971 he needed a wheelchair.

By the time Hawking became Cambridge’s Lucasian Professor of Mathematics – a chair also held by Isaac Newton – he “could no longer walk, write, feed himself, or raise his head if it tipped forward,” Ferguson writes of his condition in 1979. “His speech was slurred and almost unintelligible except to those few who knew him best.”

Hawking had several brushes with death. One occurred during a 1985 trip to Switzerland, where he became so ill that the doctors put him into an induced coma and on a life-support system. In order to save his life, Jane decided to have him undergo a tracheotomy, which was performed in Cambridge.

Hawking could no longer speak and could only communicate by spelling out words letter by letter; a helper would point to the letters on cards held out for him to see and select with a nod. Also, Hawking now needed 24-hour care from nurses.

Ferguson recounts how a computer expert in California enabled Hawking to communicate more rapidly by giving him a program the man had invented called “Equalizer.” It allowed Hawking to select words from a computer screen, and it also had a voice synthesizer – the famous Hawking voice known around the world. A student made Hawking a mouse-like tool that allowed him to operate the computer by squeezing a switch with his hand.

Because ALS continues to destroy his muscles, today Hawking can no longer use the mouse-like device. He now operates the computer by twitching a cheek muscle and thus activating a low-power infrared beam that prompts the computer.

“It is, of course, nothing short of miraculous that Hawking has been able to achieve everything he has, even that he’s still alive,” Ferguson concludes. “However, meeting him and encountering his intelligence and humor, you find yourself taking his unusual mode of communication and his obviously catastrophic physical problems no more seriously than he seems to himself. That is the way he wants it. He chooses ‘not to think about my condition, or regret the things it prevents me from doing, which are not that many.’ He expects others to adopt the same attitude.”

Although ALS has destroyed his body, Hawking plans to make further contributions to science. In a documentary produced several years ago, he declared through his voice synthesizer: “Hello. My name is Stephen Hawking: physicist, cosmologist and something of a dreamer. Although I cannot move, and I have to speak through a computer, in my mind I am free.”

Personal and institutional supports

In Ferguson’s account, Hawking has thrived so long only with the love and support of Jane and his three children with her. (ALS patients can still have sex.) Numerous professional colleagues, friends, the nurses, and other caregivers and assistants also provided Hawking with crucial support.

In the early years of the marriage, Jane cared for Hawking and coordinated the fulfillment of his needs. An intellectual in her own right, she postponed her graduate studies in literature, and she usually kept in the background as Hawking acquired accolades and fame. Ferguson reflects on how Jane chose this life path at a time when the feminist movement influenced many women to strike out independently of their husbands.

Hawking’s disease and success, as well as the presence of large number of caregivers in the home, made his marriage to Jane far from conventional. Although Ferguson does not discuss the Hawkings’ sex life during the period that they conceived their children, she does explore their ever more unusual and complex emotional and familial relationship as they lost physical intimacy. Both had affairs, and Hawking later married one of his caregivers, Elaine Mason. They divorced in 2006 amidst rumors of abuse by Elaine. At the time, Hawking refused to comment on the divorce. Ferguson indicates that no abuse took place. “The bottom line was ‘He loves Elaine,’” she concludes.

HD families also develop in highly complex ways. In addition to the debilitating symptoms, stigma, denial, and anger can lead both patients and caregivers to act aggressively, sometimes resulting in divorce or the splitting of extended families in disagreement about how to confront the disease.

However, I want to emphasize Jane’s decades-long support of her husband, and also how the family, friends, and colleagues rallied around Hawking in his battle against ALS.

The nursing staff played an especially important part. As Ferguson describes, the nurses made Hawking look nice by brushing his hair, polishing his glasses, and wiping his chin of the saliva that ran out of his mouth. They also spoon-fed him. Most importantly, they regularly cleared his throat with a “mini-vacuum cleaner” so that secretions did not build up in his lungs.

Institutional support was also crucial for both Hawking’s survival and scientific success. The British National Health Service would not pay for his 24-hour care, which the family naturally could not afford. The MacArthur Foundation, which funds academic research and other projects, came to the rescue with a grant to pay for the home care.

Ferguson points out that without such care Hawking would likely have languished in a nursing home.

Hawking’s fame and success have brought him almost endless privileges. Since 2000, he has flown frequently by private jet (paid for by others). In difficult situations, people and governments have made special accommodations for his disability.

Most disabled people can only dream of such special treatment.

The Hawkings’ advocacy

Nobody begrudged Hawking these wonderful advantages.

Recognizing the need to improve the plight of all disabled people, the Hawkings successfully pushed for greater institutional access for wheelchairs – a major struggle in the 1970s that is now often forgotten. “The Hawking image encouraged universities to set up dormitories equipped for students needing round-the-clock nurses in order to attend classes,” Ferguson writes.

Hawking firmly advocated that disabled children always be grouped with normal children of the same age.

Yearning for freedom for HD people

As Hawking’s mind remains free, I am fighting to keep my own mind free, along with thousands upon thousands of HD patients and gene-positive individuals.

In contemplating Hawking’s life, I fantasized about how wonderful it would have been for my mother to have had a device that allowed her to communicate with us from behind the horrible, impenetrable mask of Huntington’s disease.

At 52, I have reached my mother’s age of onset: each day I worry that Huntington’s will cut short my career as a college professor and writer and leave me unable to love and support my family as my daughter approaches adolescence and prepares to enter an expensive private school next fall.

Sadly for most HD people, Huntington’s destroys the area of the brain responsible for speech, thought, and memory.

Redoubling efforts for better care

The first effective treatments could arrive within the next five to ten years, but until then the HD community must focus on providing for – and demanding an improvement in – care for our stricken loved ones.

This will require us to redouble our efforts to change the nation’s outdated Social Security rules for HD people (click here to read more); provide Medicaid assistance without forcing couples to divorce and impoverish the sick individual to make him or her eligible; implement better standards of care as widely as possible; demand assistance for families caring for HD people in the home; and insist on better nursing home care. The lack of competent nursing home care remains one of the most intractable problems faced by HD families.

For now, this is our best hope for prolonging the lives of our loved ones and making their final years and months as comfortable as possible.

Perhaps HD people cannot have the advantages of a 24-hour team of expert nurses. But Hawking’s privileges point to a horizon of healthiness that humanity should aspire to for all disabled and ill people.

HD people have as much right as Hawking or anybody else to fair, decent, and up-to-date care.

In this fight, we can take a cue from Hawking.

“It is no use complaining about the public’s attitude about the disabled,” he declared at a speech at the University of Southern California in 1990. “It is up to disabled people to change people’s awareness in the same way that blacks and women have changed public perceptions.”

Let’s fix the law to help Huntington’s families

Because Huntington’s disease leaves people unable to work or care for themselves, they can qualify for Social Security and Medicare benefits. However, as many in the HD community can affirm, government bureaucracy and widespread misunderstanding of the disease make it difficult to obtain those benefits.

The Huntington’s Disease Society of America (HDSA) and HD advocates around the country are working to push through legislation in the U.S. Congress that would finally bring relief from these problems.

The Huntington’s Disease Parity Act of 2011 (House Bill 718 and Senate Bill 648) would enact two major legal changes to help HD patients.

Correcting a gross inaccuracy

First, the legislation would require the Social Security Administration (SSA) to update its long-outdated and inaccurate disability criteria for HD.

The current SSA definition considers HD only as a movement disorder. The HD Parity Act takes into account two other main types of symptoms: cognitive loss (difficulties with memory and thinking) and behavioral or psychological problems.

“The designation of this disease by the Social Security Administration as ‘Huntington’s Chorea’ is both outdated and medically inaccurate, as this term fails to recognize the behavioral and cognitive impact of Huntington’s Disease, while also providing an incomplete characterization of the full spectrum of Huntington’s Disease for purposes of Social Security Disability Insurance and the Medicare program,” the text of the bill states. (Click here for the full text of the bill.)

The term “chorea” refers to the shaking and dance-like movements suffered by many – but not all – HD patients.

Secondly, the bill would waive the two-year waiting period for patients to receive Medicare benefits, thus bringing assistance quicker to families in dire straits because of the disease’s severe impact on household finances.

How families struggle

Misty Oto, a board member for the San Diego chapter of HDSA and a leading advocate of the bill, witnessed the travails of her HD-stricken mother, brother, and aunt as they struggled to obtain benefits.

Her brother’s symptoms had caused him to miss SSA appointments, misplace paperwork, and write illegibly on his application for benefits, according to Misty. Finally, with the help of Reps. Bob Filner (D-San Diego) and Brian Bilbray (R-San Diego), the SSA reviewed the application. (Filner and Bilbray were the original co-sponsors of the bill in 2009.)

However, because of the 24-month waiting period, he died before obtaining actual benefits.

Below, you can watch the complete interview I conducted with Misty on April 8.

Gene Veritas interviews Huntington's disease advocate Misty Oto on HD Parity Act from Gene Veritas on Vimeo.

The 'Let’s Talk about HD' campaign

In its 2010 edition the HD Parity Act gained a total of 152 co-sponsors in the House of Representatives. But the bill stood no chance of passage because of the lack of a companion bill in the Senate.

The situation improved dramatically on March 17, when Sen. Kirsten Gillibrand (D-NY) introduced S. 648.

Working at the grassroots, HDSA and advocates of the bill are now seeking to drum up support in the House and especially the Senate in order to bring the legislation up for a vote.

In May, Huntington’s Disease Awareness Month, HDSA will promote the legislation by launching a “Let’s Talk About HD” campaign.

Each week HDSA will focus on a different call to action related to the bill, and on May 31 it will sponsor a national call-in day to Congress. You can watch an HD Awareness Month video by clicking here.

Aggressive advocacy needed

Allan Rappoport, a former HDSA-San Diego board member who has helped HDSA strategize on passage of the bill, stressed that the HD community needs to unite to achieve success.

“It’s not up to your Congressman to learn about HD,” Allan told me. “It’s not up to your Congressman to push that bill through. It’s not up to your Congressman to care, because your Congressman and your Senator have got thousands and thousands of people and issues that they’re dealing with.

“It’s up to the constituents, us in the HD community, to educate them, to keep after them…. And they’re not irritated by that…. They expect and they want you to be aggressive. They need you to tell them that this is important.”

To learn more about the background to the bill and how people can best lobby their Representatives and Senators, watch the full interview with Allan below.

Gene Veritas interviews Huntington's disease advocate Allan Rappoport on HD Parity Act from Gene Veritas on Vimeo.

Please act now

So far, only the Lou Gehrig’s disease community has obtained a waiver of the two-year Medicare waiting period for people afflicted by that condition, also known as amyotrophic lateral sclerosis.

Passage of the HD Parity Act is crucial for the HD community. Not only will it remedy a difficult situation for HD families. It could also inspire other disease communities to seek similar improvements in their benefits situation.

The campaign for the bill also will raise the profile of HD in the Congress and the public arena.

So please write, call, or e-mail your Representatives and Senators today, and ask your extended family, friends, and acquaintances to do so, too.

To learn more about the bill, visit the advocacy webpages of HDSA and HDSA-San Diego.

(HDSA is also sponsoring a Caregiver’s Corner webinar on Social Security Disability Insurance appeals and denials at 1 p.m. EDT on April 27. For more information, please click here).