‘Superman’ B-cells bash MS in mice

MCGILL (Canada)—Scientists have discovered a new experimental treatment that completely reverses multiple sclerosis (MS) in mice and may work the same way in humans.

MS is an autoimmune disease in which the body’s own immune response attacks the central nervous system, almost as if the body had become allergic to itself, leading to progressive physical and cognitive disability.

Jacques Galipeau of McGill University’s faculty of medicine and the Lady Davis Institute for Medical Research at Jewish General Hospital in Montreal, led the team that discovered the new treatment, named GIFT15, which puts MS into remission by suppressing the immune response.

GIFT15 is composed of two proteins, GSM-CSF and interleukin-15, fused together artificially in the lab. Under normal circumstances, the individual proteins usually act to stimulate the immune system, but in their fused form, the equation reverses itself.

“You know those mythical animals that have the head of an eagle and the body of a lion? They’re called chimeras. In a lyrical sense, that’s what we’ve created,” says Galipeau. “GIFT15 is a new protein hormone composed of two distinct proteins, and when they’re stuck together they lead to a completely unexpected biological effect.”

Unlike earlier immune-supppressing therapies that rely on chemical pharamaceuticals, this approach is a personalized form of cellular therapy that utilizes the body’s own cells to suppress immunity in a much more targeted way.

This effect, explains Galipeau, converts B-cells—a common form of white blood cell normally involved in immune response—into powerful immune-suppressive cells. Unlike their better-known cousins, T-cells, naturally-occurring immune-suppressing B-cells are almost unknown in nature and the notion of using them to control immunity is new.

“GIFT15 can take your normal, run-of-the-mill B-cells and convert them—in a Superman or Jekyll-Hyde sort of way—into these super-powerful B-regulatory cells,” Galipeau explains. “We can do that in a petri dish. We took normal B-cells from mice, and sprinkled GIFT15 on them, which led to this Jekyll and Hyde effect.

“And when we gave them back intravenously to mice ill with multiple sclerosis, the disease went away.”

For the treatment to work, MS must be caught in its earliest stages, Galipeau cautions, and clinical studies are needed to test the treatment’s efficacy and safety in humans. No significant side-effects showed up in the mice and the treatment was fully effective with a single dose.

Because the treatment works on the immune system, the researchers believe it may also be effective against other autoimmune disorders like Crohn’s disease, lupus, and arthritis and could theoretically also control immune responses in organ transplant patients.

“It’s easy to collect B-cells from a patient. It’s just like donating blood. We purify them in the lab, treat them with GIFT15 in a petri dish, and give them back to the patient, Galipeau says. “That’s what we did in mice, and that’s what we believe we could do in people. It would be very easy to take the next step; it’s just a question of finding the financial resources and partnerships to make this a reality.”

The study was published Aug. 9 in Nature Medicine.

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