Solving the puzzle of Parkinson’s disease

For both patients and researchers, beating Parkinson’s disease (PD) is a long-term war rather than a short-term battle. The key to keeping hope alive lies in achieving daily victories.

Nan Little, a PD patient for 12 years, knows this from personal experience.

The 74-year-old Washington resident has dealt with muscle weakness, cognitive decline and other major health issues from PD. Yet her diagnosis also inspired her to write a book, climb mountains, bike across Iowa, and give a speech at an international conference.

Even during the COVID-19 outbreak, she has been open to creative new activities, such as sewing facemasks that a friend of hers distributes to the homeless.

“When faced with this challenge, I asked myself, ‘What is the opportunity here?’" she says. “It's hard having Parkinson's, but it's not impossible. It opened the door for many opportunities that never would have come my way without it.”
 

If Little makes it sound easy, that’s far from the reality. She talks candidly about her “off-times,” when she struggles.

“I’ll wake up to go to the bathroom in the middle of the night, and I have to push my own legs to the edge of the bed,” she says. “Then I use a chair to stand up. Then my feet don’t work correctly.” It takes several minutes just to start moving, she says.

Her morning begins with a regimen of leg lifts, wall push-ups, tai chi and cycling. “Then my legs are finally working well enough that I can go down the stairs,” she says.

Just recently, she began having 50 to 60 hallucinations a day. “My office is on the second floor, and I would see somebody standing outside the window,” she says. “I would look at a fire hydrant, and it appeared there was a child playing there. It was spooky.” Happily, those uninvited “guests” stopped coming after about two weeks.

Socializing is also a challenge. As she notes, “By the time you understand what someone has said, the rest of the group has moved on. You get really quiet at parties.” She tries instead to have one-on-one conversations.
 

Little fights back every day, exercising intensely to slow down her disease. Her hard work pays off.

In 2011, she climbed Mt. Kilimanjaro at age 66, becoming the oldest female PD patient thought to accomplish this feat. She also has pedaled across Iowa six times, at 450 miles per trip, in an annual recreational ride sponsored by the Des Moines Register. She has climbed the Himalayans and hiked to Machu Picchu, in Peru.

All this, and yet she still has trouble typing at times.

“The challenges vary every day,” she says. “With Parkinson’s, you don’t know what kind of day, or even hour, you’re going to have.”

That “whack-a-mole” pattern for PD patients is familiar to Michael Gold, M.D., vice president, neuroscience development, AbbVie. When he was a physician, his own patients reported the same daily challenges popping up.

“I took care of patients for many years, and the frustration of not being able to offer them truly meaningful therapies is one thing that drove me into industry,” Dr. Gold says. “Anytime I can work with novel compounds that hold promise, it’s very exciting. We are crafting new science almost daily. My colleagues are writing new chapters all the time.”

Gold says in the past 20 years, science has shifted from dealing only with symptoms to tackling the underlying causes of PD. Genetics, molecular biology, systems biology and other pathways are all under the microscope.

“Where we were 20 years ago, in research, compared to where we are now is not even comparable,” he says. “We’re a world ahead.”

For example, researchers are studying:

• the buildup of a misfolded (malformed) protein called alpha synuclein in the brain, which spreads from neuron to neuron and causes the loss of dopamine-producing cells
• problems with autophagy, the way the body removes proteins within its own cells
• the deleterious effects of toxic substances produced by aged body cells that should die, but don’t

Discoveries and collaboration are paving the way to new solutions.

“We always need to stay humble,” Dr. Gold says. “We’re all smart people working in this field, but it is very important to recognize that there are many good ideas being worked on and which we should be open to.”

There is no cure for PD, but patients like Nan work with their doctors to slow the disease’s progression, stay healthy and keep racking up those daily wins. AbbVie’s research continues to support those goals, Dr. Gold says.

“For us, quality of life and the ability to maintain independence and personhood, that is core to our organization,” he says.

For Nan, there are also golden moments, when she forgets about her disease.

“When I’m fly-fishing or doing something spectacular, it’s a Zen-like state,” she says. “Parkinson’s isn’t there anymore. Those are some of the best times.”