A talented artist, Karri Knudtson worked at the former Coventry Glassworks in Appleton and at first kept up her own art on the side. Even as the responsibilities of motherhood began to take over, everyone was envious of how she could whip up a sketch of a new way to decorate her home, said her sister, Shawn Boogaard.
But then something else started to get in the way. Knudtson’s body began to move involuntarily and her moods became unpredictable. In 2015, she was diagnosed with Huntington’s disease, a rare genetic condition that causes a person’s nerve cells in their brain to break down over time.
The last picture Knudtson sketched was of her three children when they were little, gazing into the tub, all ready for a bath. She died in March at 57.
The disease depletes motivation, which made it even more challenging for Knudtson to connect with her artistic talents. But after her death, the family gathered her sketches together and put them on display at the glass gallery in August.
“When we found her artwork we thought, people need to know that she lived with this disease and it affected her greatly,” Boogaard said. “But she still had this incredible talent.”
Those who know Huntington’s describe it as a triple threat of sorts, combining the most detrimental symptoms of Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis, better known as Lou Gehrig’s disease. It hits adults in midlife, showing up between age 30 and 50, and slowly deteriorates body, brain and emotional function until it kills them.
Progression of the disease looks different in everyone. It often begins with clumsiness and difficulty multitasking; people develop problems with balance, speech and swallowing, lose the ability to drive a car or work. Cognitively, they start to experience depression, irritability and bouts of rage. It eventually causes dementia.
What’s more, it’s an inherited disease, in which the children of someone who has it have a 50% chance of getting it themselves. Thus it can devastate families like Knudtson and Boogaard’s — their grandmother and uncle had it, and, as they discovered when Knudtson was diagnosed, so did their father, though his symptoms were mild enough to go undetected for a long while.
Only about 40,000 Americans, or one in every 8,000, have Huntington’s disease, with an estimated 200,000 more who are at risk. So although the condition is a devastating one, the people whose lives it touches are a tight-knit, supportive community, waiting on a scientific breakthrough that might stand a chance at stopping neurodegeneration.
Today, that breakthrough could be closer than ever. And Wisconsinites — including two UW-Madison researchers and a former Neenah man enrolled in a promising trial for a treatment — could play a major role in getting there.
New trials could pave the way from ‘symptom management’ to real chance at slowing disease
Robert Cockhill had a feeling he knew what was going on when he began slipping up at work in Las Vegas a few years ago.
His father was diagnosed with Huntington’s disease at age 50, and in five years he was “a shell of himself,” Cockhill described. So he went immediately to see his father’s doctor: Dr. Kathleen Shannon, a movement disorders specialist who now chairs the neurology department at the University of Wisconsin School of Medicine and Public Health. There, Cockhill confirmed what he’d already suspected: He had it, too.
Shannon has been working on human clinical trials to find medicines to manage the symptoms of Huntington’s since the 1990s, when scientists identified the gene that is responsible for the disease. After moving from Chicago to Wisconsin, she earned a Center of Excellence designation from the Huntington’s Disease Society of America for UW Health’s Neurology Clinic — the first and only center in the Badger State.
UW’s center brings in nearly 200 families with the disease to receive comprehensive care from a number of medical professionals, including top neurologists, psychiatrists, social workers and therapists.
“The disease evolves over time, so you need a practiced hand to keep a person as good as they can be,” Shannon said. “That’s really the art of Huntington’s disease management.”
For decades, that’s how the disease has been handled: Symptom management, with no real way to stop or slow down the progressive changes to people’s bodies and brains.
But that might change soon. And Cockhill — who is from Neenah and now lives in New Braunfels, Texas — has been able to participate in not one, but two clinical drug trials that could eventually make that change.
After beginning to see Shannon, he contacted researchers at the University of Toledo and was enrolled in 2016 in a trial launched by the Huntington Study Group and the pharmaceutical company Vaccinex for an antibody that could slow the progression of brain inflammation in people with Huntington’s.
When that study concluded, he looked around for another and found the final-stage clinical trial of a drug from the Swiss pharma company Roche. In the Roche treatment, a synthetic piece of DNA attaches to messenger RNA and degrades the message telling the body to make the protein huntingtin, which clumps together when the gene inside it mutates and “gums up” the cells, causing neurodegeneration, Shannon explained.
Cockhill flies to Seattle every two months to get an injection into his spinal fluid. Like in the University of Toledo study, he has no idea if he’s getting the trial drug or a placebo. But a few years into his diagnosis, his symptoms have not gotten dramatically worse, as his father’s did and as he expected them to.
“It’s a thousand times better than winning the lottery,” he said of being a two-time trial participant. “I’d rather feel this way the rest of my life than have a billion dollars.”
Disease prevention is the ‘holy grail,’ and one Wisconsin researcher is looking for it
But not everyone is as lucky as Cockhill.
It took years for doctors to agree to test Knudtson for the disease, Boogaard recalled, because their father’s disease had gone undiagnosed. It doesn’t skip generations, so if neither of her parents appeared to have it, doctors thought she couldn’t either.
“We believe if she would have been diagnosed earlier, a lot of things that were difficult for us to deal with could have been prevented,” Boogaard said. “We would have had a much better understanding of what she was going through.”
Because of its rarity, most primary care physicians go their entire careers without seeing a patient with Huntington’s disease, Shannon said, and that limited experience can breed late diagnosis.
What would be better is early detection. And what would be best, of course, is something that would prevent disease progression altogether.
Jane Paulsen, a research faculty member within UW-Madison’s neurology department, believes she has a secret weapon. For years, she’s studied people who carry the mutated Huntington’s gene but aren’t sick yet to look for indicators of the disease that could make treatment possible earlier and earlier, maybe even in time for prevention.
In 2001 at the University of Iowa, she launched PREDICT-HD, which followed 1,400 people around the world for 12 years and was one of the first studies to show that brain, motor, sensory, behavioral and social changes could be identified in people more than a decade before a traditional diagnosis of Huntington’s.
Now in Wisconsin, Paulsen is looking for new study participants to continue her work. She wants to be able to shift the design of such studies from therapeutic trials, which measure how well a drug can treat a disease, to prevention trials, which determine whether a drug prevents a disease.
Paulsen’s research was critical to start building an understanding of when doctors should start treating people that have the mutated Huntington’s gene, Shannon said, because if the sweet spot can be found, symptom onset could be stopped completely.
“That’s the holy grail,” Shannon said. “It’s not a cure, but it’s as good as a cure, because you won’t get sick.”
As research ramps up, families wait and wonder
Four people in Boogaard’s family, including Boogaard herself, have never been tested for Huntington’s, despite the possibility that it will target several more of them as it winds its way through generations.
None of them have had symptoms, and they’ve all already had their children.
Without a cure, “there’s always a part of us that says, ‘Do you really want to know?'” she said.
For so many people who could carry the mutated gene, that’s the frustration, said Deb Zwickey, a retired behavioral health therapist who leads a support group in Oshkosh for families living with Huntington’s disease. Some want to plan ahead, she said; others don’t want an early death sentence.
Managing the support group for the Wisconsin chapter of the Huntington’s Disease Society of America is the highlight of her career, she said. There are other groups in Milwaukee, Madison and Eau Claire, and her group is meeting twice a month via Zoom since the COVID-19 pandemic hit.
“One of the reasons why (the groups) have been so important is it’s such a rare disease,” Zwickey said. “When somebody finds a commonality like that, they really stick together.”
Patients, caregivers, spouses, children and friends gather in an open and honest environment to discuss the struggles that the disease can bring, and the fear and uncertainty that riddles the time before and after a diagnosis. But Zwickey says she also tries to emphasize the hope that’s coming, some of it in the form of the work Shannon and Paulsen are doing.
The experimental interventions that have emerged in the last few years have been “wildly exciting,” Shannon said. There’s significant stigma associated with Huntington’s because of its serious side effects, she said, but with the major pushes that have been made recently, “we’re seeing it come out of the shadows.”
Paulsen agrees. In the past, doctors treated brain diseases by simply dampening symptoms as much as possible, she said, and she’s witnessed many a treatment that worked like that.
But these advancements are different.
“It didn’t have the hope we’re seeing now,” she said. “This hope is real.”
Contact Madeline Heim at 920-996-7266 or [email protected] Follow her on Twitter at @madeline_heim.