Few scientists know Huntington’s disease as intimately as Jeff Carroll.
An Army vet who trained with top Huntington’s scientists at Harvard University and the University of British Columbia, Carroll is a widely published researcher, award-winning advocate and sought-after speaker at Huntington’s disease conferences around the globe.
He’s also guaranteed to get the disease.
Carroll, an assistant professor of Psychology at Western Washington University, inherited HD from his mother and grandmother, both of whom died from it. If he lives long enough, he’ll watch it devour three of his five siblings, too. The first drug trial to ever target the cause of Huntington’s in humans – a trial he and other scientists are calling the most promising yet – began in September. Nobody has ever cured a degenerative brain disease, but this trial may be the closest scientists have come. A half-dozen other drug trials, too, are providing promising glimpses of potential treatments for HD symptoms.
Science moves with fastidious care, though, and Carroll knows a cure isn’t likely before he dies. Huntington’s symptoms – memory loss, personality changes, involuntary movements – typically develop in midlife, between ages 30 and 50. Carroll is 38.
“I hope for the best and prepare for the worst,” he says. “I act like it’s going to kill me, but I hope and I believe that it won’t.”
The disease may take his life, but Carroll isn’t letting it take his days. Not while his research needs attention, his students need mentoring, his wife needs her husband and his kids need their dad.
Not while the disease keeps burning its way through family trees.
Carroll applied for tenure at Western this September. He’s been at WWU since 2011, arriving the year after completing his doctorate at UBC. In between, he conducted post-doctoral research with Marcy MacDonald, one of the world’s top researchers of neurodegenerative diseases, at Harvard Medical School.
Not many kids who drop out of high school make it to Harvard. But not many kids have Carroll’s motivations, either. A decade before opening his lab at Western, Carroll had been serving in the Army, his future a nebulous blur. And then he learned that his mom was dying of Huntington’s. Desperate for any information that might provide hope, he began a lifelong pursuit of the disease.
“When Jeff found out about HD in his family, he basically turned his whole life upside down,” says Amber Southwell, a friend and post-doctoral researcher at the Centre for Molecular Medicine and Therapeutics at UBC.
Today, with British researcher Ed Wild Carroll runs a website called HDBuzz that helps HD families – people, like him, hungry for scraps of anything to make sense of this thing – stay abreast of the science and any treatments or trials that may prove effective. The site is written in plain language, aiming to inform. At the end of every story, readers can click either “Enjoyed” or “Didn’t understand.”
The site is a purveyor of hope, Wild says. Patients are no longer alone, blindly hoping for a cure. Instead, they’re able to share in daily research victories.
“There’s as much hope to be had from basic breakthroughs and understandings as there is from major trials,” he says. “Often, that’s all that’s needed. I can affirm that there is hope, that there are lots of little, small things to hope for. We slightly, sort of, a little bit, kind of changed the world.”
Carroll’s work with HDBuzz and his other outreach work to fellow HD families are the reasons he and Wild were named 2014 Researchers of the Year by the Huntington’s Disease Society of America.
First human drug trial
Room 532 is a busy space on the top floor of Western’s newest building. On a typical day, Carroll’s lab in the Academic Instructional Center buzzes with activity. In one room, students are monitoring a Morris water maze to gauge how HD affects mice’s memories. In a dark space across the hall, the glowing screens of high-end microscopes illuminate the intent faces of students.
The primary research in Carroll’s lab focuses on testing whether turning off the HD gene in the body can help the brain get better.
“It probably won’t work, honestly,” Carroll says. “But if it does, it’s super cool, because it’s way easier to dose people in the periphery than in the (central nervous system). Even if it helped a little bit, it’d be a new avenue to consider.”
Actually, everyone has the HD gene, one copy from each parent. In most cases, the gene exists harmlessly at the end of chromosome 4, providing instructions for cells in making the HD protein. But in roughly five to seven people per hundred thousand, one of those genes is mutated.
Scientists aren’t exactly sure of the purpose of the HD protein, but they know it’s required for normal development before birth. Mice bred to lack the HD gene die in utero.
Wild likens gene mutations to spelling mistakes.
The Huntington’s “spelling mistake” is a repetition of the nucleotide bases represented by the letters C, A and G at the beginning of the gene. If those letters are repeated at least 36 times, you’ll get HD. Guaranteed. Carroll has 42.
Carroll’s research might reveal more about the function of the HD protein. “The mice give us the opportunity to discover whether the loss of (the HD protein) in peripheral organs is detrimental,” he says. “We’re using the mice like the canary in the coal mine.”
In London and Vancouver, scientists have just begun human trials that look at the effect of silencing the HD gene in the nervous system. Thirty-six patients will eventually be enrolled in the trial of a drug targeting not the symptoms, but the disease itself. Animals treated with the mouse version of the drug have shown improvements in HDlike symptoms, but there’s a long way to go before the drug could be widely used in people. Still, scientists have been excited for more than a decade about this trial beginning.
“The whole field is beside itself,” says UBC’s Southwell. “It’s a very, very exciting time.”
The trial uses a drug that aims to prevent cells from using the HD gene to create proteins. Mutant genes provide instructions for making abnormal proteins, which in turn damage the brain. The drug gets in the way of that. Southwell explains: “If genes are the menu, mRNA are the orders and proteins are the meals, this drug destroys orders for huntingtin proteins on their way to the kitchen.”
Wild, a consultant neurologist at the National Hospital for Neurology and Neurosurgery at University College London and one of the trial’s investigators, puts it another way: “The drug shoots the messenger.”
Scientists hope that the drug will cut the production of HD proteins in half. And that’s just about perfect, Wild says. This trial is about as safe as it can be given the state of research, he says. It’s a massive step forward.
“Whatever the result of this safety trial, the fact it’s happening is one of the most important steps in HD research since the gene was discovered in 1993,” Wild says.
‘What am I doing?’
Carroll grew up just south of Seattle, one of six children born to parents Jim and Cindy. He describes his younger self with words you might find on a bad report card: directionless, underachieving, failing to live up to potential. He dropped out of high school, attended Green River Community College for a bit and then joined the Army in 1996. Stationed at Fort Lewis, he spent his weekends in Vancouver, B.C., where he met his wife, Megan; they married while he was stationed in Germany.
Then on Christmas leave in 1998, Carroll’s dad told Jeff that his mom had been showing signs of Huntington’s disease.
“My wife tells me that I must have known on some level what Huntington’s disease was, because I reacted very emotionally, while she genuinely didn’t know what my dad was talking about,” Carroll told a group of scientists at the 10th Annual HD Therapeutics Conference in February. “We were married, but I had never told her about my risk for HD, because in my mind, I didn’t know.”
But now he knew – and wanted to know more. In 1999, Carroll was sent to Kosovo as part of a peacekeeping force. In his downtime, he spent hours scouring the fledgling Internet for information about HD. There wasn’t much. Eventually, he gave up and enrolled in a college correspondence course in biology.
He enrolled at the University of British Columbia in 2001 after being discharged from the military. He didn’t know it then, but UBC is home to the Centre for Molecular Medicine and Therapeutics, which itself contains one of the world’s most advanced Huntington’s research labs, led by Michael Hayden.
It was there in 2003 that he was tested for Huntington’s.
Carroll was faced with a life-changing decision. He had just learned that he had a disease that would steal his mind, strength and personality, probably by the time he was middle-aged. Now two years into his schooling, how much more time did he want to spend inside laboratories and offices?
“I had this crisis of conscience,” he remembers. “‘What am I doing? This is taking so long.’”
Many students reach this point during the long doctoral slog, Carroll says, even those who aren’t fated to lose their knowledge prematurely.
“It was at that point that I definitely made the decision,” he says. “It’s like, if you don’t fill up your brain with stuff because you’re worried you’re going to lose it, then you’re giving in.”
Southwell, who met Carroll in 2009 in Hayden’s lab at UBC, says she’s known of other researchers from HD families, but none who’ve risen to Carroll’s level.
“You make some hard choices about how you want to spend the time you have, and not everyone makes the decision Jeff made,” she says. “We are very lucky that he’s made the choice he has.”
Knowing that Carroll fights on against an uncured disease inspires researchers to try even harder, Wild says.
“Everyone in the HD community wants to work rapidly enough to come up with treatments to help Jeff,” he says. “Within the HD community, Jeff is pretty much everyone’s hero. That’s sappy, but it’s true. He’s my hero. What he’s done, going from being a grunt to being one of the world’s leading HD researchers, is kind of a Disney-esque story. It’s a story of triumph over adversity, of dogged human endeavor.”
Wild recalls a conversation in which Carroll told him that his life is much more interesting because HD is in it.
“HD has defined his life,” Wild says. “But he’s had control over how it has defined it.”
Clad in a white V-neck shirt, dark grey hoodie and jeans, Carroll evokes images of Macklemore as he holds sway in class. Students describe him as brilliant, enthusiastic, passionate, hilarious. Carroll doesn’t often talk in class about having HD, but everyone knows about it. It’s just a fact of Carroll’s life.
“Sometimes you have to put your personal struggles aside if you want to make a difference,” says Western junior Jose Carrillo, who has been working in Carroll’s lab since his freshman year. “He does that. I think that’s part of what makes him a great scientist.”
Carrillo was born in Peru. When he was 7, his parents moved the family to Indiana so he and his brother Eduardo would have access to stellar education. Carrillo’s getting that at Western, he says. He wants to be a clinical researcher, and Carroll has been mentoring him toward that goal.
“If I had to pick one person as my role model, whether in science or in life,” Carrillo says, “it would be Jeff.”
‘We don’t know what to do with him’
Huntington’s disease is famously linked to folk musician Woody Guthrie. The “Dust Bowl Troubadour,” who spent much of his early years chronicling the lives of migrant workers during the Great Depression, is probably best known for the 1940 anthem “This Land is Your Land.” Later that decade, as his behavior became increasingly erratic and violent, Guthrie was diagnosed both as an alcoholic and a schizophrenic, according to Joe Klein’s 1980 biography “Woody Guthrie: A Life.”
“Mrs. Guthrie, your husband is a very sick man,” a doctor once told his wife, Marjorie. “And we don’t know what to do with him.”
These days, information is much more prevalent and accurate, Carroll says.
“Yeah, we can’t cure HD yet,” he says, “but you can get much better information.”
Treatments for symptoms of Huntington’s disease do exist. Drugs help suppress involuntary jerking and writhing – Huntington’s chorea – in some patients. Antipsychotic medications sometimes lessen mood swings or violent outbursts. Physical therapy can help patients maintain mobility. But these treatments only mitigate aspects of the advancing disease; nothing has been proven to slow the progress of Huntington’s.
“You’re going to die when you’re going to die,” Carroll says. “In that sense, it’s incurable, and that’s what people tend to focus on when they find out about it.”
But there are many incurable brain disorders, he adds. Part of having a human brain is the fact that, eventually, it falls apart. Like HD, Alzheimer’s is incurable. Parkinson’s is incurable. And scientists don’t even know why certain people get sick.
“Why did Joe’s grandma get Alzheimer’s when she was 70, but your grandma lived until she was 90? Well, we don’t know,” Carroll says. “If you want to treat those people, you can’t find them until they get sick. Something like 90 percent of the neurons in the substantia nigra are dead by the time you have Parkinson’s. By then, it’s pretty late to try to fix it.”
Huntington’s is unusual among diseases that attack the brain: Baked into its genetic core is an early warning system. The gene mutation that causes Huntington’s is detectable from an early age. From the embryo stage, really.
Many people know years, even decades, before symptoms appear. Those years can represent anxiety – or hope.
“If we could find treatments or therapies, drugs, that modify the course of the disease, we could give it to them early, before they get sick,” Carroll says.
Carroll’s children will not inherit this disease
Since 1993, when the mutation was discovered, thousands of patients have been able to plan ahead for Huntington’s. People can even – as Jeff and Megan have – ensure that their children will be HD-free.
The Carrolls’ twin children, Billie and Elijah, were born in 2006. They will never get Huntington’s disease, because doctors examined the embryos and implanted in Megan only the ones that were mutation-free. They were the first children born in Canada via this process, and they’re well-known in the research community.
“My mom’s generation, they had no choice,” Carroll says.
“I have six kids in my family, and all of us were born before the mutation was found. It didn’t matter; if you wanted to have kids, you just had them. To me, once that technology existed, it changed everything. Before, it was this unanswerable family fight.”
Billie’s and Elijah’s drawings are taped all over Carroll’s office. Houses with smoke curling from crooked chimneys. Trees, laden with fruit, standing tall under a yellow sun. All drawn by kids who’ll never lose their ability to hold a crayon because of Huntington’s. Carroll loves talking about it.
But the kids are still part of an HD family, one of thousands of HD families. And that means his work isn’t done.
“The brain is insanely complicated,” he says. “I’m not that old, but there have been huge revolutions in biology and neuroscience since I started. Things that I was taught in my training were wrong. And not little things, but big, huge things. So, who knows what’s going to happen?”
Carroll, Southwell, Wild and other researchers know today what scientists years ago could only hope was true.
“By definition, all of the problems of HD can, in theory, be reversed,” Wild says.
To Carroll, that’s reason enough to keep hoping, to keep fighting. To keep filling his brain – and those of his students – with information that might one day end Huntington’s.