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Disorders
By Beth Howard

Promising Therapies May Help Huntington’s Disease

Researchers are pursuing therapies that may alter the course of this inherited neurodegenerative condition.

Sarah Foster first knew something was wrong in 2005 when she kept forgetting she had an infant. "He would be asleep in the other room, and I would suddenly realize, 'Oh my gosh, I have a son,'" says Foster, then 39. "Every time I would forget and remember it again, I would freak out. How could I forget the existence of someone so precious to me?"

Illustration of woman holding a baby
Illustration by Maria Hergueta

By 2009 Foster had developed mood issues and become prone to angry outbursts and impulsive behaviors that caught the notice of her co-workers at the New Bern, NC, school where she taught special education. "They said that the person who came back to school in the fall was totally different from the one who was there last spring," she recalls.

Foster could no longer ignore these problems and made an appointment with a genetic counselor at the University of North Carolina at Chapel Hill. Given her family history, she suspected Huntington's disease (HD), a rare genetic disorder that causes the breakdown of the brain's nerve cells. Her grandmother, great-aunt, and great-uncle all had experienced similar symptoms and been diagnosed with the disease (her mother probably had it too but was never diagnosed). None underwent genetic testing.

When Foster got her test results in December 2009, she was devastated. "I stayed in bed for weeks crying and was more depressed than I have ever been in my life," she says. "And I felt so alone and lost and doomed. I asked myself why the coin had to flip that way. I wanted a do-over but knew the information was accurate."

Foster went back to work after the Christmas break, but "it was clear to me on many levels that I couldn't continue," she says. "I left that day, and I never went back." She is now a technical copy editor, a job with flexible hours that allows her to work from home.

For Foster and her husband, Randy, who is also her caregiver, the past decade has been a relentless scramble to manage her growing assortment of symptoms and live as normal a life as possible. "Everybody says it's an invisible disease," Foster says. "You see the face I put on, but underneath it's like every single cell I have is fighting to approximate normal behavior."

Wide-Ranging Effect

HD, a progressive and fatal disease, "causes a triad of symptoms—motor, psychiatric, and cognitive," says Erin Furr-Stimming, MD, associate professor of neurology at the University of Texas Health Science Center McGovern Medical School in Houston. "Most individuals become symptomatic in their forties, during the prime of their life, after which the symptoms continue to worsen, robbing them of their ability to walk, talk, and live independently."

Around 30,000 people in the United States have HD, according to statistics compiled by the National Institute of Neurological Disorders and Stroke. Additionally, about 150,000 to 250,000 people in the United States are believed to be at risk for the disease, says Jee Bang, MD, MPH, assistant professor of neurology at Johns Hopkins University School of Medicine and clinical director of the Johns Hopkins Huntington Disease Center of Excellence. Most people with the condition develop symptoms between ages 30 and 50, but some develop them after 55. Huntington's disease that develops before age 20 is called juvenile HD, Dr. Furr-Stimming says.

The disorder begins in the striatum, part of the basal ganglia deep within the brain, but over time it affects the entire brain. It's caused by a single known genetic mutation, called huntingtin, which controls the production of a protein found in nerve cells throughout the brain. "HD is inherited in an autosomal dominant manner, meaning that each child born to a person with HD has a 50 percent chance of inheriting the condition," says Amy Shealy, MS, a genetic counselor at the Cleveland Clinic's Comprehensive Huntington Disease Clinic.

Diagnosis often starts with a medical and family history, along with tests of balance, movement, muscle tone, hearing, walking, and mental status. A genetic test that identifies the mutation is required for a definitive diagnosis. "People can be tested once they have symptoms, or people 18 and older can choose to be tested without symptoms to determine if they will develop HD someday," Shealy says.

The decision to get tested can be fraught. "There are psychological, familial, and sometimes insurance and employment factors to consider prior to testing," says Shealy. "We ask people to think about why they want testing and how they believe results would impact them."

Foster worries about her three sons, ages 14, 19, and 21, who are at risk. "Both of my older sons are happy, and they don't want to know," she says. "I don't push them because I want them to enjoy life."

HD has been compared to having Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease all at once. "It takes so much from people," says Herminia D. Rosas, MD, director of the Center for Neuro-imaging of Aging and Neurodegenerative Disease at Massachusetts General Hospital in Boston. "It changes their personality and destroys their intellect and motor control. It takes away everything gradually, insidiously, and progressively."

The most common movement symptom is chorea, which is characterized by abrupt, jerky, irregular, and unpredictable movements. Behavioral and psychiatric symptoms include depression, anxiety, irritability, apathy, impulsivity, and obsessive tendencies. And the disease often leads to cognitive decline and dementia.

"You can have one, two, or all three types of symptoms, or start out with one but get additional symptoms, or one symptom may subside while another begins, or just mainly be affected in one type the entire time," says Dr. Bang. "It's not possible to exactly predict how each person's symptoms will progress, even if we know exactly how his or her parent's course was."

Progressive Symptoms

Foster has been relatively untouched by the movement symptoms of HD, but she has struggled with cognitive deficits, including memory lapses and behavioral changes. "Right now I'm having trouble with compulsive behaviors, particularly shopping and eating, that I'm working on with my psychiatrist," she says.

Huntington's symptoms often occur without a person's awareness, which brings its own set of problems. "Many patients have what we call anosognosia, or a lack of insight or lack of awareness of their symptoms," says Dr. Furr-Stimming. "We'll often see that there's so much collateral damage that's occurred before people actually receive a diagnosis: lost jobs, broken relationships, substance abuse, and even suicide attempts." (Suicide is the second most common cause of death among patients with HD, Dr. Furr-Stimming says.)

Unfortunately, symptoms worsen over time and always lead to death. "The average range of life expectancy is 15 to 20 years after diagnosis," says Dr. Bang. "But there are many individual differences and outliers." Ongoing studies are looking for additional genes that influence the course of HD, among other characteristics of the disease, he says.

Although there is no cure, the outlook for patients has brightened in recent years. "Currently no treatments slow the progression," says Dr. Bang. "However, for the first time ever, we have experimental drugs that could help treat the symptoms, as well as slow progression. These medications are being administered to volunteers with HD in clinical trials right now."

Promising Treatments

In a New England Journal of Medicine study in 2019, one drug successfully lowered levels of the toxic huntingtin protein in the central nervous system. "Normal huntingtin protein is important in many cell functions," says Dr. Bang. "But the mutant form, which occurs when one has the mutant huntingtin gene, is harmful to many of the brain cell functions and is thought to be the main cause of HD symptoms."

Experts are cautiously optimistic that new drugs will make a difference. "Exciting gene-modifying or huntingtin-protein-lowering therapies are being tested in humans," says Dr. Furr-Stimming. "We have an advantage with HD: We know the causative gene. We can't say that about Parkinson's disease, ALS, or Alzheimer's disease. If we can modify the gene or the gene product, we hope to make significant progress in slowing progression of HD."

Beyond experimental medications, there are numerous options for alleviating symptoms. Ideally, families that have the gene for HD should be followed in a clinic where they can receive support from multiple providers, such as psychiatrists, social workers, neurologists, neuropsychologists, genetic counselors, and physical and speech therapists, Dr. Furr-Stimming says. "Our goal in treating individuals with HD is to optimize quality of life," she says.

Among the drug options is tetrabenazine (Xenazine), an FDA-approved medication for the involuntary movements of chorea. "In addition, a few other medications can effectively treat chorea," Dr. Bang says. "For mood symptoms, we choose from a multitude of medications that can treat anxiety, irritability, depression, obsessive-compulsive behavior, and, to a lesser degree, apathy."

That includes amantadine (Symmetrel), an antiviral that is used to control tremors in people with Parkinson's. It's part of the ever-changing cocktails of drugs that Foster takes to control her HD symptoms. "It alleviates or ameliorates the apathy," she says. "It's given me the will to get through a day and engage."

Foster also relies on anxiety medications and antidepressants, including aripiprazole (Abilify) for other behavioral and mood symptoms, and the ADHD drug lisdexamfetamine dimesylate (Vyvanse), which helps with impulse control. "I started taking that a month ago because I've been having problems with binge eating and shopping," she says. "Not only has it taken away those impulses, but it also has given me the ability to experience a happiness I haven't felt in years."

Practice Self-Care

Lifestyle approaches also may help. "My neuropsychiatrist told me that establishing good sleep habits—avoiding napping, going to bed at a regular time—is one of the most important things I can do," says Foster. "He's also recommended meditation, which is really neuroprotective."

Dr. Rosas stresses the importance of nutrition. "Patients tend to lose weight, and as people lose weight, their other symptoms, particularly their motor symptoms, get worse," she says. "We try to make sure people eat frequently throughout the day. That really seems to help avoid episodes of hypoglycemia, which can happen with this disease."

Exercise can protect brain health in addition to its strength and conditioning benefits, says Dr. Bang, who recommends enlisting the help of a physical therapist to make sure the type and intensity of the exercise are appropriate and safe.

Foster remains hopeful about the development of a medication to slow or stop her disease. "When I first got diagnosed, I started going to the conferences and keeping up with the research," she says. "Seeing how slowly things move, I'm kind of guarded. But if something comes my way, I'm there as a guinea pig."


Resources for Huntington's Disease

Brain & Life
Huntington's disease

Hereditary Disease Foundation
hdfoundation.org; 212-928-2121

Huntington's Disease Foundation
hdfoundation.org

Huntington's Disease Society of America
hdsa.org; 800-345-4372

National Organization for Rare Disorders
rarediseases.org; 203-744-0100


Join a Huntington's Disease Trial or Registry

Researchers are seeking new ways to treat the symptoms of Huntington's disease (HD) and developing medications for clinical trials. To enroll in a trial, visit clinicaltrials.gov and type "Huntington's disease" in the search field. Here are an ongoing sample trial and a patient registry.

Drug Trial

Patient Registry

  • What: An observational study of Huntington's patients who can contribute information for clinical data and biospecimens for research to develop therapies and identify biomarkers
  • Where: 175 sites around the world
  • For more information: Email Qura Ain at info@enroll-HD.org
  • Link: clinicaltrials.gov