Researchers are exploring the mysterious effect of Parkinson’s disease on movement disorders.
Liz Ogren, who was diagnosed with Parkinson’s disease in 2007, stands on a weight-sensitive floor while wearing reflective markers on her body so that her gait can be tested in the Movement Disorders Laboratory at the University of Minnesota in Minneapolis April 25, 2014. (Courtney Perry/Special to the Star Tribune)
Don Spicer was out walking with his wife, Jackie, about two years ago when he suddenly came to an unplanned halt.
“My right leg was just like it was in a pool of cement,” the Bloomington 71-year-old recalled. “I just couldn’t move.”
Spicer has “freezing-of-gait,” an exasperating and mysterious condition that can be triggered by an abrupt turn, a long hallway, a narrow doorway or seemingly nothing in particular.
Liz Ogren, 51, of Edina, was on a mountain-biking trip in Canyonlands National Park in Utah when she was struck by a similar disorder called dystonia, which wracks the body with involuntary muscle contractions. She found herself locked in a rigid, horizontal position while rock climbing in a keyhole canyon. “I begged people to get me down,” said Ogren, a retired fifth-grade teacher. “And I was a really good rock climber.”
No one knows what causes freezing-of-gait or dystonia, but both can occur in individuals with Parkinson’s disease. Spicer and Ogren both sought help at the University of Minnesota, where a large and growing team is working to unravel the mysteries of these movement disorders.
Under the leadership of Dr. Jerrold Vitek, a world-renowned researcher and neurologist, the university has been building an interdisciplinary team to study Parkinson’s from the molecular level through clinical treatments.
Vitek, who grew up on Minnesota’s Iron Range, hopes to build a Parkinson’s research program of national stature and join the federally funded Morris K. Udall Centers of Excellence for Parkinson’s Disease Research consortium, which provides up to $1.5 million a year in funding.
Parkinson’s disease, now personified by the actor Michael J. Fox, afflicts about 1.5 million Americans, making it the most common movement disorder and second-most common neurodegenerative disorder after Alzheimer’s disease. But in a sense, Minnesota is a natural site for such a research center. Nebraska, the Dakotas and Minnesota have the nation’s highest statewide prevalence of Parkinson’s, possibly because of high use of pesticides. More than 15,000 Minnesotans have the disorder, a number that is expected to double by 2040.
The latest addition to the U’s research effort is a new lab to study freezing-of-gait under the direction of Colum MacKinnon, a neurophysiologist Vitek recruited from Northwestern University.
Here, subjects are fitted with gumball-size reflectors and hooked into a harness connected to computer cables suspended from an overhead beam. They walk several paces as high-resolution cameras record their movements in 10-millisecond increments. Sensors beneath a suspended floor record minute changes in pressure, which display as hyperactive fever charts.
In essence, the data capture the physics of movement, MacKinnon said. The study will compare people with freezing-of-gait against normal control subjects and other Parkinson’s patients who have other movement disorders.
MacKinnon said freezing-of-gait is hard to study because it occurs intermittently. Even so, the patients have distinctive characteristics. Normally, a person shifts from one leg to the other while walking. But with Parkinson’s, MacKinnon said, “what happens is they lift their foot up off the floor and they start to fall. So every time they take a step forward it’s like this controlled fall.” Sometimes they lose control and collapse.
“The remarkable thing,” MacKinnon added, “is that when they’re stuck … if you give them a flash of light, if you give them a sound, if you tap them on their shoulder, they’ll walk,” he said. But the cue must be perceived as coming from an external source. Like tickling, it can’t be self-imposed.
MacKinnon and his team, working with a three-year, $750,000 grant from the National Institutes of Health, are trying to determine the best way to cue a person who’s stuck.
Searching for ‘biomarkers’
Parkinson’s occurs when cells in the brain stem that produce dopamine cease to function, though no one knows why that happens. The cell death works its way higher into the brain. The peripheral nervous system that controls walking and other voluntary limb movements remains viable, but the control center in the brain sends incoherent messages, resulting in slow movements, tremors or rigidity. Parkinson’s symptoms vary considerably.
“We’ve discovered a lot of genes now in Parkinson’s. But we’ve also discovered 18 to 20 genes in dystonia, and a number of years ago we would have told you there was one,” he said. “So there’s a lot of ways to end up with Parkinson’s symptoms.”
Dr. Paul Tuite, co-director of the U’s clinical practice in Parkinson’s, has directed more than 30 clinical trials researching Parkinson’s since joining the U in 1996 and is co-investigator for a Michael J. Fox study called BioFIND that is looking for biomarkers to diagnose and track the disease as it progresses.