ACTRIMS 2026: Blocking C3 protein seen to ease MS severity in older mice

Complement system own to reduce disease severity in older mice

Written by Lila Levinson, PhD | February 9, 2026

The complement system — part of the immune system that helps defend against infections — may play a key role in age-related disease progression in multiple sclerosis (MS), according to findings from a mouse study.

In fact, blocking a complement protein called C3 reduced disease severity in older mice but not in younger ones, the researchers saw in using a mouse model designed to mimic progressive disease.

“We found that inhibition of C3 activation in aged but not young mice resulted in milder disease,” the team wrote in a study abstract.

Valeria Ramaglia, PhD, a professor of immunology at the University of Toronto, presented these findings at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026, held last week in California and virtually. The talk was titled “Complement as Driver of Age-dependent Progression: Insights from a Mouse Model and MS.”

New research is now underway to determine whether targeting the C3 protein could be a potential treatment strategy in MS.

Age is one of the main risk factors for disability progression in MS, but the biological processes behind this are not fully understood.

Researchers suspect that inflammation in the leptomeninges — membranes that surround the brain and spinal cord — may drive this progression. Immune cells have been shown to form clusters in those membranes and release harmful molecules into the spinal fluid that damage nearby brain tissue.

One vulnerable structure is the hippocampus, which plays a role in learning and memory and sits close to both the leptomeninges and spinal fluid-filled brain cavities.

Researchers create model to studying disease processes

To study how age affects these processes, the team created a mouse model that recapitulated leptomeningeal inflammation, with animals showing clusters of immune cells in these membranes. The model was created by transferring inflammatory immune cells primed to cause progressive MS from donor mice into healthy mice.

The researchers transferred the immune cells into animals of different ages, and found that age clearly determined the course of the disease.

“If we transfer … cells into young mice, the mice get sick, but they recover. But if we transfer them into aged mice, they get sick and they stay sick,” Ramaglia said.

Additionally, the older mice showed persistent signs of inflammation in the leptomeninges and significant damage in the hippocampus relative to healthy animals. In the young mice, these features resolved.

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