MS Society of Canada Grant Supports Trial of Metformin in Young Patients

Multiple Sclerosis Society of Canada have given CA$400,000 (about $312,500) to support a pilot clinical trial investigating the potential of metformin, a common diabetes therapy, to treat children and young adults with multiple sclerosis (MS).

The Phase 1/2 feasibility trial (NCT04121468) is recruiting up to 30 patients, ages 10 to 25, at two sites in Toronto. Those interested may find additional information here.

MS is an autoimmune disease characterized by the damage and loss of myelin — the protective layer around nerve fibers that is crucial to the effective transmission of signals in the central nervous system.

Most MS treatments are aimed at suppressing the immune system and reducing inflammation to protect the myelin coat. They are not able to reverse the myelin damage done by the disease.

A team of Canadian researchers proposed that treatment with metformin might be able to induce brain repair, and lessen disability in children and young adults with MS. Their project is titled “Approaches to Repairing Damaged White Matter in Children and Young Adults with MS.”

Preclinical studies by this team, included in the project, showed that metformin promoted motor and cognitive recovery by increasing the production of oligodendrocytes — cells that produce myelin — in animal models of MS.

These researchers also found that metformin showed an ability to repair white matter — brain regions composed mainly of myelin-coated nerve fibers — in children with radiation-induced brain injury.

Now, the research team intends to determine if these findings will hold in a placebo-controlled, pilot trial investigating if metformin can promote brain repair in young MS patients.

“Our team is very excited about being able to move this trial forward, and for the collaborations across multiple different scientific areas that the collaborative grant will allow,” Ann Yeh, MD, trial’s leading investigator, said in a press release.

“This is truly a team effort that started at the bench at SickKids [The Hospital for Sick Children, University of Toronto] — in the lab of Dr. Freda Miller — and has set the stage for a clinical trial that could potentially improve outcomes for children and young adults living with MS,” Yeh added.

Patients enrolled in the yearlong study will be divided into three groups, according to the time period they are assigned to start taking a 500 mg daily dose of metformin — at three, six, or nine months. A placebo is being given during the period in which participants are not receiving metformin.

All will be on metformin, an oral type 2 diabetes treatment in use in Europe since the 1950s and the U.S. since the 1990s, for at least three and up to nine months.

As primary outcomes, the trial is assessing the treatment’s feasibility, tolerability, and patient satisfaction over three years. Secondary goals include assessments of neurodegeneration through optical coherence tomography (OCT). OCT measures the thinning of nerve fiber layers in the eye, which are associated with the loss of brain volume and other measures of MS activity and progression.

Changes in neuronal activity and patients’ physical disability are other secondary outcomes, which also are being measured over three years.

“This trial is a unique opportunity to advance novel therapies that target regeneration and repair to help reverse the progressive nature of MS by re-purposing a safe, low-cost treatment,” said Pamela Valentine, PhD, president and CEO of MS Society of Canada.

Stem Cell Network (SCN) and the Ontario Institute for Regenerative Medicine (OIRM) also provided funding to this trial. Together with the MS Society’s investment, the trial has CA$1 million (about $781,550) in financial support.

“The MS Society is thrilled to partner with SCN and OIRM in funding this project that has the potential to change the life course, and transform treatment and care for youth and people living with MS,” Valentine said.

Of note, Canada has one of the highest rates of MS in the world. According to the MS Society, an average of 12 Canadians are diagnosed with the disease every day.