When Amy Aungst was growing up, she saw nearly every person on her mother's side of the family struggle with Huntington's disease. This included her grandfather, mother and three uncles.
In 2015, at age 26, she found out that she has the genetic mutation that causes Huntington's disease, but has yet to experience symptoms. This clarity helped her plan for a family and guided her decision to participate in research studies, which have been supported in part by the National Institutes of Health, to help investigators better understand the condition and move closer to identifying new types of treatment to help people like her live better and longer.
"I really want a different outcome for Huntington's disease," says Aungst. "I've seen it affect my whole family my whole life."
"It's tough to watch everybody get sick," she adds. "You live in constant worry."
The condition, which is rare, is estimated to affect about 7 out of 100,000 people, or 30,000 people or more in the U.S. It starts with alterations in the HTT gene, which provides instructions to help the body produce the protein huntingtin. This protein normally supports everyday functions such as movement, cognition and emotion.
The condition was first described by the physician George Huntington in 1872. About 120 years later, in 1993, investigators identified the HTT gene mutation. This discovery catalyzed the field, and researchers have been studying ways to therapeutically target the mutation. They are also studying how variations in other genes — particularly those involved in DNA repair — can accelerate or delay the onset of symptoms in people who carry the HTT gene mutation.
Each person typically has about 10 to 35 repeats of cytosine, adenine and guanine (CAG), which make up the amino acid glutamine in the huntingtin gene. When there are too many CAG repeats — typically starting at 40 or more — symptoms of Huntington's disease often appear. The extra CAG repeats result in abnormally long stretches of glutamine amino acids in the mutant huntingtin protein, which can cause the protein to misfold, clump together and become toxic to brain cells.
Physical symptoms vary, but often include involuntary movements called chorea, which can look stilted, jerky or fidgety (and are often compared to being dancelike). Huntington's disease can also create issues with memory, thinking, social perception, feelings and the ability to regulate behavior. Around 4 in 10 people with Huntington's disease also experience depression.
Huntington's disease symptoms can occur at any time, but often appear between ages 30 and 50. Once symptoms occur, a person typically lives for another 15 to 20 years. However, survival rates vary and can range from five to more than 25 years (and often depend on individual factors).
This timeframe is what Aungst hopes to change.
She wants to live for as long as she normally would without the condition, or at least make it possible for future generations. She also wants to watch her children and any future grandchildren that she may have grow up.
Since having the HTT mutation brings a 50-50 chance of passing the disease to offspring, Aungst and her husband — like many families with Huntington's disease — opted to adopt their children. They are now the proud parents of two young boys.
Aungst credits advancements in research with helping them to make this decision. For example, her grandfather received a brain autopsy after he died, which is how her family learned that he had the condition. She and her mom both had blood tests, which were unavailable to her grandfather's generation, and received the results in weeks.
As Aungst watches other research advancements unfold, she hopes that when she does experience symptoms, there may be a trial she could enroll in to test a new treatment to slow the progression of the disease or at least better manage its symptoms.
"I'm at the age where I could start showing symptoms at any time," she says. She has seen Huntington's disease be manageable, including one family member who lives independently and walks with a cane. Others have required full-time care and support.
"There are good reasons to have hope," says Jee Bang, M.D., M.P.H., clinical director of the Johns Hopkins Huntington Disease Center of Excellence. Bang shares that major research advancements, including recent FDA-approved medications for the treatment of chorea, are a result of and thanks to partnerships with study participants, like Aungst, who are helping investigators study different facets of the disease.
Bang explains that while there is currently no cure for Huntington's disease, researchers have been studying ways to slow its progression by using therapies to lower levels of the huntingtin protein or silence its genetic expression.
These approaches vary and include using experimental gene-based therapies to target the expanded CAG repeats in the huntingtin gene, lower overall levels of the protein, or target genes involved in DNA repair that influence how quickly symptoms develop.
Investigators are also still studying "here and now" treatments to help people manage symptoms, Bang explains. This includes using different medications to improve mobility and control chorea as well as other treatments and approaches, such as psychotherapy to address symptoms like depression, anxiety, irritability or obsessive thinking and behaviors, and cognitive training and music therapy to help support people affected by problems with thinking and memory.
Ultimately, Bang adds, combinations of treatments will likely be needed at different times. "Even though it's one gene that's affected, it's still a complicated and comingled process," she adds.
As research advances, investigators continue to study different aspects of Huntington's disease to understand its molecular underpinnings, how it affects people differently and how this knowledge could inform the use of different treatments and their timing.
For example, Bang explains that cerebrospinal fluid, a clear liquid that surrounds and cushions the brain and spinal cord, is being studied for its ability to provide additional insight about what is happening in the brain. These types of markers, especially when paired with traditional measures like blood samples, could help investigators gauge when early signs of Huntington's disease appear and how someone may respond to different treatments.
The ultimate goal, Bang notes, is to see if huntingtin-lowering therapies given at the earliest sign of rising protein levels could significantly delay or stop symptoms before they occur.
Meanwhile, Aungst continues to work with her team to detect early signs of physical symptoms of Huntington's disease, and lives life as she normally would with her family in Milton, Delaware.
For the past eight years, Aungst has teamed up with a man in Delaware who also has family members with Huntington's disease. Together, they organize walks around nearby Cape Henlopen State Park to raise awareness about the condition. Her family comes down from Pennsylvania for every walk to support it.
"I want people to know what Huntington's disease is, how it affects people, how we can gain knowledge and how we can change outcomes," she says.
"We've made huge gains since I've been around," she adds. "Everything seems so optimistic."
