In these scans, compare the size of the illuminated dopamine-producing cells in the Parkinson’s patient on the right with the production levels of the typical brain on the left. (Image courtesy of James Boyd)
James Boyd, M.D., UVM Associate Professor of Neurological Sciences (Photo: COM Design & Photography)
In 2009, Parkinson’s disease patient Cassandra Blanchard would walk her youngest daughter to the school bus stop near her house in Randolph, Vt., and then find herself unable to get back home, because her medication had worn off.
“I had on and off fluctuations that were horrible,” Blanchard says.
The drugs she took would help her regain function, but a couple of hours later, she’d suddenly weaken. “I’d get stuck in grocery stores” and particularly while shopping among crowded racks of clothing, Blanchard says. “I’d freeze, and I couldn’t move. My son had to just pick me up and carry me out.”
Blanchard’s doctor James Boyd, M.D., a University of Vermont neurologist and Associate Professor of Neurological Sciences, had witnessed her and other patients’ similar struggles when their Parkinson’s disease progressed and sudden drops in their medications’ effectiveness debilitated them.
So when the opportunity came for UVM to join a clinical trial for a treatment with the potential to help Parkinson’s disease patients level out those “low periods,” Boyd jumped. UVM was one of 31 institutions that tested an innovative pump-based system that delivers steady, small doses of medication throughout the day. Called Duopa, the treatment received U.S. Food and Drug Administration approval in January 2015.
Parkinson’s disease is a disorder of the nervous system caused by the loss of brain cells that produce the chemical dopamine. The disease impacts movement, sometimes starting with a tremor in the patient’s hand and progressively leading to loss of more motor function.
The standard treatment for Parkinson’s, an oral medication called levodopa, boosts the level of dopamine. The drug revitalizes the patient, but when the amount in the bloodstream tapers, someone with more advanced Parkinson’s ends up hindered for several minutes to hours until the next dosage kicks in. These low periods could happen several times a day, Boyd says, keeping otherwise active people from doing the things they want and need to do.
“You could be spending up to a third or half of your day incapacitated,” he says.
Blanchard, who is 50 years old and was diagnosed with early onset Parkinson’s disease in 2002, had to stop playing outside with her grandchildren and building snowmen or sledding with them in the winter. She had to take the bus everywhere.
“I wasn’t even driving anymore,” she says, adding that those restrictions on her life convinced her to join the trial when Boyd offered it. “I wasn’t able to be me; I was becoming less and less of myself.”
Duopa, which combines levodopa and the companion drug carbidopa in a concentrated gel form, is delivered through a tube inserted surgically through the patient’s stomach and into the intestine, so medication absorption is steady and consistent. Patients carry a somewhat clunky electronic device – about the size of a portable video game console – that pumps a continuous infusion of the drug throughout the day – just enough to facilitate mobility, but not so much that patients experience side effects such as jerky, involuntary movements.
The stronger doses, Blanchard says, would increase these movements, turning her into something like actor Jim Carrey’s disjointed character in the movie “The Mask,” in which he yells, “Somebody stop me!”
AbbVie Inc., the North Chicago, Ill.-based pharmaceutical company that developed Duopa, conducted the U.S. portion of the study in 125 patients who experienced at least three hours and averaged more than six hours of “off” time in a day. Its system reduced those debilitating periods by an average of four hours, according to AbbVie.
“You’re able to give people back four hours of functional time in a day,” Boyd says. “It’s yet another tool in our arsenal, so to speak, to maintain their function.”
The primary downside of the drug system, and the biggest challenge for patients, is the need to lug around the pump equipment. Having a tube inserted also carries a risk for infection and a chance that the tube may fall out or malfunction.
“Most of the people felt like the relative burden of having that pump was far better than the burden of the symptoms it alleviated,” Boyd says.
Blanchard admits she felt wary about the trial, particularly the surgery to place the tube and the hassle of carrying the pump. Boyd gently encouraged her, sending her home with materials to think about it, she says.
When she did decide to take the plunge and use the pump, “it made such a difference,” she exclaims. On Duopa, her breathing immediately eased – usually her muscles were so tight before she took her medication that she struggled to draw air into her lungs – and she felt loose enough to get out of her hospital bed after five or 10 minutes.
“I went out to the nurse’s station and did a little circle,” she recalls. “It was just awesome! I call it my Cinderella medicine, because it brings me back to me.”
For Boyd, the trial took an intensive effort. Patients spent two to three weeks in the hospital after insertion of the tube while he and his team adjusted their dosages to get the right infusion at the right pace. He was on call for them 24/7, often up at dawn and checking on them into the night, he says.
Among the small percentage of patients who qualified for the trial, UVM had a high level of participation – seven patients – even compared with larger institutions. Most patients eagerly agreed not only to improve their own quality of life but also to provide information that Boyd and other physicians can use to better treat Parkinson’s disease, he says.
Since Duopa hit the marketplace, two more UVM patients have gone on it, Boyd says. Existing patients in Vermont will meet with new ones, visiting them in their homes to walk them through all the details, he says.
“It was really pretty awesome,” he says. “I couldn’t have predicted the emotional response that people had in terms of the positive impact this had on their function.”