Addressing a major treatment gap
MS is a chronic autoimmune disease that attacks the central nervous system, disrupting communication between this system and the rest of the body. Possible symptoms include pain, mobility challenges, vision problems, fatigue and bladder or bowel dysfunction. According to MS Canada, Canada has one of the highest rates of MS in the world, with 90,000 Canadians living with the disease, 75% of them women.
Pilutti explains that relapsing MS is the most common form of MS, where people experience episodes during which symptoms suddenly worsen, almost like flare-ups. These attacks are followed by periods of remission, and this cycle of relapse and recovery can repeat itself over many years. But in progressive MS, symptoms gradually worsen over time, and disability accumulates without clear recovery periods.
According to Pilutti, most of the existing medications and therapies available target the relapsing form of MS. This creates “a big gap” for people living with progressive MS, who, despite representing about half of the MS community, have far fewer effective treatment options.
From planning to a multi-site trial
This funding marks the second stage of the International Progressive MS Alliance’s Well-being Research Pipeline, a multi-stage initiative designed to move promising ideas from planning to large-scale testing and, ultimately, real-world implementation.
The Alliance funding pipeline features three stages. More than 60 teams applied for Stage 1 funding in 2023, and 9 were selected, including Pilutti’s. This first phase focused on planning and collecting pilot data, while Stage 2, which only three projects have advanced to, will test the team’s intervention in a large, multi-site randomized controlled trial. Six Canadian institutions will be participating, along with partner sites in Italy and the United Kingdom.
Preparing the brain to learn
Pilutti’s study, titled “Can Priming Enhance Rehabilitation Success in Progressive MS? The Can-PRIME MS Trial,” combines rehabilitation with what the researchers call “brain priming.”
Participants will attend intensive sessions three times per week for eight weeks. The rehabilitation is task-specific: people identify the motor or cognitive challenges they face in daily life, such as walking long distances, navigating complex environments or performing upper-body tasks, and the program is tailored accordingly.
“We want this to translate into everyday improvements for people who are living with progressive MS,” Pilutti emphasizes. The approach is personalized and participant-driven, focusing on real-world function rather than laboratory-only outcomes.
Before each 40-minute rehabilitation session, participants will complete 20 minutes of “priming.” This could involve aerobic exercise, non-invasive brain stimulation, or a combination of both.
Pilutti explains that the approach is grounded in neuroplasticity, the brain’s ability to adapt and form new connections. In progressive MS, some neural pathways are disrupted, making it harder for signals to travel efficiently.
The rationale for priming is to stimulate the brain before rehabilitation, making it more responsive to training. Activities such as aerobic exercise or non-invasive brain stimulation could help “prepare” the brain, increasing its receptiveness to learning during the subsequent rehabilitation session.
The central question, Pilutti says, is whether priming can enhance the effects of rehabilitation, and if so, whether one type of priming works better than another.
Measuring long-term impact
Participants will be assessed at the beginning, midpoint and end of the eight-week intervention, with followups extending over two years. In addition to motor and cognitive outcomes, the research team will examine quality of life, health-care use and long-term disability progression.
Stage 2 also includes focus groups with health-care providers to explore the feasibility of implementing this intervention in clinical settings. These discussions will help inform a future Stage 3 application, which would focus on integrating the program into health-care systems more broadly.
The study also adopts a patient-oriented approach. An advisory panel of people living with or affected by MS is providing ongoing input throughout the project.
Progressive MS presents unique challenges because symptoms and disability vary widely from person to person, says Pilutti. By combining personalized rehabilitation and brain stimulation techniques, this MS trial aims to offer new strategies for addressing that challenge. Final reports from the three Stage 2 studies funded by the Alliance are expected within four to five years.