Research sheds light on how to slow progression of multiple sclerosis

A study led by University of Toronto researchers has uncovered crucial insights into how the progression of multiple sclerosis may be slowed down.

The research by Jen Gommerman, professor and chair in the Temerty Faculty of Medicine’s department of Immunology, and Angela Wang, a PhD candidate and first author on the study, was recently published in Science Translational Medicine and involved co-authors from around the world.

The research looks at the role of an anti-CD20 drug therapy — ocrelizumab — and how taking the drug affects the white blood cells (specifically, B cells) of a person living with multiple sclerosis (MS).

The researchers were curious about the finding that these drugs affect a protein called B cell survival factor (BAFF) and wondered if this was related to the efficacy of the drug. Indeed, inhibiting BAFF with the drug atacicept failed as a treatment for MS.

Gommerman and Wang’s research used an animal model to study how anti-CD20 drug therapy affected grey matter demyelination of the brain, and then, if it did, its relationship to a person’s BAFF.

Ultimately, Gommerman and Wang’s research shows that using ocrelizumab prevents grey matter damage in the brains of mice models developed to aide the research, as well as boosts BAFF in cerebrospinal fluid and other membranes that surround the brain and spinal cord.

“If you are a person living with MS, grey matter demyelination of the brain is what you worry about because we don’t know how to treat it,” says Gommerman, who holds the Canada Research Chair (Tier 1) in Tissue Specific Immunity.

“White matter demyelination is very predominant early in the disease. It causes episodes of disability, but as you progress in the disease, the grey matter demyelination becomes worse and worse and it leads to a lot of clinical burden, including cognitive dysfunction.”

There is no known cure for multiple sclerosis, but there is much research underway into how to best treat the disease, including the world by Gommerman and Wang.

In Canada, there are more than 90,000 people living with multiple sclerosis, and that number rises to 2.9 million people affected worldwide. Seventy-five per cent are women, according to MS Canada, and Canadians have the highest rate of MS in the world.

The recent discovery by Gommerman and her colleagues is critical because it firmly establishes the relationship between using ocrelizumab, and a person’s BAFF.

“We were able to causally link the efficacy of ocrelizumab with BAFF levels,” says Gommerman, who is also a co-director in the Canadian Hub for Health Intelligence and Innovation in Infectious Diseases (HI³).

She states that for patients with MS, “You want to get rid of your B cells, but you also want to have high levels of BAFF. Ocrelizumab achieves that but atacicept does not, because it gets rid of the B cells, but it blocks the BAFF.”

Gommerman says the research holds important takeaways for the future of multiple sclerosis treatment and staving off the progression of MS — giving patients “more confidence” in their futures.

“If we can figure out how to elevate BAFF even more in anti-CD20 treated patients, then that becomes a potential adjunct therapy to stave off disease progression,” she says.

Gommerman also emphasized the research was the result of multiple parties, and pointed to new ways of approaching problems, in future.

“These are really complicated questions that require multiple labs to be able to tackle, and it really means partnerships between basic scientists like me and clinician scientists,” she says. “This is really the path forward for complex diseases like MS. We really have to work together to investigate the disease from new angles.”