First-ever study by MGH Institute and the MGH Multiple Sclerosis and Neuromyelitis Optica Unit to examine efficacy of combining Multiple Sclerosis drug with physical therapy.

Slowly, Ann LaSpina rose from her chair to both feet, then raised her left foot, gingerly keeping her balance.  

“Time to let go of my hand,” said Dr. Prue Plummer, a professor of physical therapy and Multiple Sclerosis specialist at the Department of Physical Therapy at the MGH Institute’s Sanders IMPACT Practice Center. “Keep most of your weight on your left foot and slowly turn your head side to side.” 

LaSpina, diagnosed with relapsing remitting Multiple Sclerosis in 2005, followed the instructions. Then it was time for LaSpina to switch most of her weight to the right side, the one more affected by her MS.  

“Oh, my goodness,” she said. “This is harder.”  

Plummer then had LaSpina close her eyes, stand on two feet, and turn her torso side to side with a weighted ball. By closing her eyes, LaSpina couldn’t use her vision to help with balance, and the weighted ball shifted LaSpina’s center of mass, which meant she had to work hard to maintain that balance.  

“Great job,” said Plummer. “You’re doing really well.” 

An estimated 90% of people with MS experience difficulties walking, due to the damage that occurs to the nervous system. In particular, the signals that travel along the nerves between the brain and the muscles are slowed down in people with the condition. 

LaSpina has been receiving an infusion of Tysabri – a disease-modifying therapy drug to contain the underlying inflammation – every six weeks, and dalfampridine – known as the “walking pill” – for the past two years, which she says has helped. But for the past three weeks, the 59-year-old has been combining dalfampridine with physical therapy and says that’s what has made a world of difference.  

“I would say I’m at 50-75% better now,” said LaSpina. “I have more balance, stability, and strength with the combination of the pill and doing the physical therapy. I used to lose my balance frequently, but that’s not happening anymore. My muscles are being built up.” 

prue puts her hands on ann to steady her in a gym
Ann LaSpina (right) listens to PT Professor Prue Plummer during a treadmill session.

A first-ever study 

LaSpina is part of a first-ever study looking at the combination of the walking drug dalfampridine and physical therapy.  

Researchers have long known that physical therapy can help the walking gait by assisting the brain to make new connections, but this requires a lot of time. And because physical therapy may create changes in the brain, the improvements can last longer, even after a person stops PT. Dalfampridine works on potassium channels in the central nervous system to help to speed up the signals between the brain and the muscles. But it doesn’t work well in everyone, and once a person stops taking it, any improvements are immediately lost. 

No one has ever studied whether taking the tablet while simultaneously receiving PT can improve how well a person responds to the treatments – until now.  

This research collaboration between the MGH Institute and the Massachusetts General Hospital Multiple Sclerosis and Neuromyelitis Optica Unit will take this first look into whether combining these two treatments can improve walking more than either treatment can do on its own.  

Plummer is working on the study with Dr. Eric Klawiter, an Associate Neurologist who heads up the hospital’s unit. The duo has applied for a grant that will examine 48 MS patients over a three-year period, but they already are examining pilot participants like LaSpina.  

“What we found in our preliminary work is that if we give physical therapy to the patients who are getting the drug, they can make improvements beyond what the drug does alone,” says Plummer. “I really hope it will lead to a better collaborative partnership between neurology and PT so that they recognize that effect the pill for walking may be augmented by simultaneous physical therapy, thereby increasing not only the number of responders to the medication, but also the size of the therapeutic benefit.” 

Plummer and Klawiter believe the two treatments– one that makes the nerves send signals faster (medication), and one that helps the brain to “rewire” itself (rehabilitation) – may complement each other. The study’s goal is to compare the combined treatment (tablet with PT) to each treatment on its own, and to compare the two individual treatments to each other (tablet versus PT). 

The study is novel because it will be the first to:  

  • Directly combine these treatments and directly compare them to each other  
  • Look at changes in the brain associated with each treatment and the combined treatment 

 “The results have potential to make an immediate impact on how the medication and PT may be prescribed for people with MS,” said Dr. Klawiter. “With the use of functional MRI, the findings will also impact the scientific community by evaluating how these treatments modulate functional brain networks and connectivity.”  

The researchers are also hoping to learn if study respondents will retain more of their physical therapy gains if they combine PT with the tablet after all treatment ends.  

“It’s exciting to see how we might be able to propel gains in Multiple Sclerosis by simply examining two proven methods that help people with MS walk, and seeing if they’re better together,” said Plummer.  

Back on MGH Institute campus, LaSpina is walking on the treadmill at 1.1 miles per hour, up from 0.8 miles per hour in her previous session. She’s not holding the rails as Plummer asks her to list as many animals as she can while maintaining her balance and cadence. The task is designed to see how LaSpina does when her brain isn’t focused only on walking and to practice under distracted conditions.  

“Dog, cat, elephant, deer, giraffe,” LaSpina rattles off. “Pig, cow, crocodile, fish, rabbit, hamster.”  

LaSpina’s gait is good. Then Plummer adds another task. 

“Name as many cities as you can, any place in the country. The Wakefield resident stays regional.  

“Brockton, Brookline, Malden,” says LaSpina. “Did I say Boston? Boston, Malden, Medford, Wakefield, Melrose, Arlington.”  

As the cities and towns are listed, LaSpina’s balance on the treadmill isn’t as solid as it was moments ago during the animal listings.   

“What do you think you’re focusing more on,” asks Plummer, “the cities or your walking?” 

“I guess I’m focusing more on the cities and that’s messing up my walking,” admits LaSpina.  

“Good job,” reassures Plummer. “We’ve only started that distraction task with walking – that’s more difficult.” 

It’s only been three weeks since LaSpina began receiving physical therapy and taking the walking pill, but Plummer is encouraged with the progress.  

“We're seeing a lot better motor control on her more affected side, which is her right leg. We're still working on some adaptability with the walking on the treadmill and maintaining that cadence and control when she's distracted,” says Plummer. “I think we take for granted that we’re doing things a lot of times when not focusing on walking. We deliberately build those sorts of distractions into the training so that patients can recognize when they're unstable, and they can stop and focus on what's more important.” 

With four weeks left in the pilot program. LaSpina is more hopeful than ever what her result might be. She has already shed her AFO (ankle-foot orthosis) brace.   

“I do take the pill,” said LaSpina, “but the rehab is the key. You definitely need both because they work better together.” 

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prue has red hair and black rimmed glasses, ann has brown short curly hair and a yellow top
“I would say I’m at 50-75% better now. I have more balance, stability, and strength with the combination of the pill and doing the physical therapy. I used to lose my balance frequently, but that’s not happening anymore. My muscles are being built up.”
- Ann LaSpina (right), with IHP PT Professor Prue Plummer