Canadian media highlights Medicine by Design-funded research that informed MS treatment clinical trial

Reposted from Medicine by Design.

In multiple sclerosis (MS), a disease of the central nervous system, the immune system is attacking the covering of nerves, called myelin. The symptoms that result from those attacks can affect a person’s mobility, vision and cognitive skills, among other impacts.

The metformin research in Cindi Morshead’s lab focuses on protecting against this damage. Metformin is an approved drug widely used in diabetes treatment. Canadian news outlets CityNews, CTV News and 680 News featured the research over the month of May, which is MS Awareness month.

Recently, Morshead’s team published a paper of findings related to metformin treatment for MS. In an animal study, 40 percent of the animals who were given metformin did not show any MS symptoms when they were treated at the time of disease onset, and those that did have some disease progression fared better than the animals who were not given metformin.

“So this was remarkable in the sense that it looked like it was decreasing the severity of the injury … when you gave metformin, you could spare the myelin … it was a protective effect,” Morshead, who is professor and chair of the Division of Anatomy, Department of Surgery, University of Toronto (U of T), said to CityNews reporter Dilshad Burman. Morshead’s lab is at U of T’s Donnelly Centre for Cellular and Biomolecular Research.

Currently, there are several disease therapies for MS that reduce symptoms and slow the progression of the disease, but none that remyelinate the nerves and/or repair damage that has already occurred.

The results from the Morshead lab, along with other research studies, have helped to inform a clinical trial currently recruiting at The Hospital for Sick Children (SickKids) led by Ann Yeh, a staff physician at SickKid’s Division of Neurology.

Metformin’s effect on stem cells

Stem cells have natural healing properties. Morshead is part of a large-scale team project funded by Medicine by Design that has the goal of activating that capability to repair the body in neurological and muscular disease.

More than 10 years ago, a researcher at The Hospital for Sick Children (SickKids), Jing Wang, working in the lab of then-SickKids scientist Freda Miller (now a professor at the University of British Columbia), found that the common and long approved diabetes drug metformin seemed to help make new neurons in the brain. Miller is also a Medicine by Design-funded investigator who leads the team project associated with this research.

Since then, a group of researchers including Morshead, Miller and Donald Mabbot, a senior scientist at Sickkids, have looked at administering metformin in several contexts other than MS including in spinal cord injury and for children who have had cranial radiation to treat brain tumors.

“We asked the question, ‘would we be able to repair the injured brain by activating the resident stem cells that are found in the nervous system?’” said Morshead in the CityNews story.

Study points to potential impact of early metformin administration

In the MS study, the Morshead team found that the positive effect they observed seemed to be time limited – if metformin was administered later in the disease progression, it did not seem to produce the same result.

“So this said that if patients are presenting at an early age with MS then giving this safe drug may be able to stave off some of the detrimental effects that the disease would have. That’s the importance of the early administration,” says Morshead in her CityNews interview.

Work has helped to launch a clinical trial

Yeh said in the CityNews article that her team launched the clinical trial because of the preclinical work by Morshead and other metformin researchers. The clinical trial’s funders include the Stem Cell Network and MS Canada.

“Let’s say a definitive randomized control trial is performed and it’s positive — there’s such great things that could come out of that,” Yeh said in the CityNews article.

Currently, the trial is enrolling patients in the 10- to 26-year-old age group. It has enrolled half the required number of participants needed to begin the trial.

If the trial shows positive results, she says metformin’s status as a safe, approved drug that is generally well tolerated may make it straightforward to integrate into a patient’s treatment regimen.

“As a clinician caring for young people with multiple sclerosis, I’ve seen a revolution in the way that we treat MS, but I think that we still need to do more. This is where the future lies, in really understanding whether we can figure out things that have regenerative potential,” Yeh said to CityNews.