Multiple sclerosis: how to halt its progression?

Did you know that more than 90,000 Canadians are living with multiple sclerosis (MS)? That’s more than the number of people with HIV in the country. And yet it’s not widely talked about.

Nathalie Arbour and Catherine Larochelle, researchers at the CHUM Research Centre (CRCHUM) and neurosciences professors at Université de Montréal, along with Drs. Alexandre Prat, Pierre Duquette and Marc Girard, are tracking the molecules responsible for MS in the brain.

Even though the causes of this autoimmune disease are still poorly understood, scientists know that dysregulation of the immune system “encourages” T-cells, white blood cells responsible for activating the human body’s defence against infection, to attack healthy nerve tissue in the body’s brain and spinal cord.

The disease targets myelin, the protective coating that surrounds nerve fibres, which causes inflammation and finally leads to the deterioration of this substance, which is essential for the transmission of nerve impulses. MS causes disabling vision, memory, balance and movement problems that vary in severity and duration.

May is the MS Society of Canada’s MS Awareness Month, and to mark it here’s an overview of the latest research work Arbour and Larochelle are conducting on this chronic inflammatory disease.

A fragile immune balance

In their laboratories, the two scientists always begin their research with observations made on patients or their tissue before validating it with animal models. This approach is what sets them apart on the Canadian research scene.

In one of her recent studies, Arbour observed that the T-cells from patients respond much more strongly to interleukin 15 (IL-15) than those from healthy controls.

IL-15, a protein produced by white blood cells following an infection or inflammation, increases the activation and proliferation of T-cells and has pro-inflammatory properties.

When Arbour and her team injected IL-15 into mice with a disease resembling MS, they showed that the disease symptoms of the animals worsened.

“In this study,” said Arbour, “we had access to blood samples of patients who had the progressive form and others who had the relapsing-remitting form of MS. This allowed us to show that there were immunological mechanisms common to both forms of the disease that could be targeted by therapeutic interventions.”

Complex mechanisms

In a second study, Arbour focused on another protein, interleukin 27 (IL-27). Its anti-inflammatory properties have already been demonstrated in animal models and it decreased the severity of the disease in mice.

Human biology is more complex, however. Arbour saw an increased presence of IL-27 in the brains of patients who had died of MS, but its anti-inflammatory effects on the patients’ T-cells seem limited compared to what was observed in healthy donors.

For Larochelle, a better understanding of alterations in the immune system in humans will, in the long term, promote the development of personalized treatments that will allow patients to regain immune balance and live symptom-free.

Renowned expertise

For over a decade, the work done by the basic research teams of Arbour, Larochelle and Prat have garnered international acclaim.

Beyond their expertise, their success was built on their strong collaboration with outstanding neurologists at the CHUM’s MS clinic – Dr. Marc Girard and Dr. Pierre Duquette, recipient of the CRCHUM’s Bâtisseur Award – and on the wealth of the samples in their biobanks.

“Today, the high-quality data from MS clinics and from research work contribute to a large international database with data on more than 60,000 patients,” said Larochelle. “This allows us to contribute to global efforts to help clinicians in Canada and around the world understand how to choose the right treatment at the right time for the right patient.

Arbour and Prat are also co-directors of the neuroimmunology component of the CanProCo study, a Canadian prospective cohort study that will track disease progression in multiple sclerosis patients for five years. In Canada, only five sites are participating in the study and in Quebec, only one: the CHUM.

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