It was early 2010, and the research team in Dr. Freda Miller’s lab at the Hospital for Sick Children had just made an exciting discovery: they’d identified a crucial pathway for telling developing neural stem cells to make neurons and glia in the brain.
“It was a very basic science discovery,” says Dr. Miller. But, with the support of funding from Brain Canada, that fundamental discovery has gone on to underpin a decade of translational research that has the potential to benefit countless young people with a range of brain diseases and injuries.
In 2012, Dr. Miller, along with co-investigators Dr. Cindi Morshead, Dr. Donald Mabbott and Dr. Paul Frankland, were among the recipients of a $1.5 million research grant from the W. Garfield Weston Foundation – Brain Canada Multi-Investigator Research Initiative (MIRI) Grants competition.
“This grant came at a critical time. It allowed us to work as a team. And it allows us to do the difficult work of taking the kinds of basic research I do in my lab to animal models, and eventually to humans. That’s a rare thing.”
The research team, led by Dr. Miller, sought to determine whether metformin, a type 2 diabetes drug that was known to activate the same pathway they had discovered in neural stem cells, could enhance the genesis of brain cells and in doing so, promote brain repair in the injured brain. To enhance the translational potential of their research, the studies were conducted in both mice and humans, with a particular focus on brain repair in children.
“My lab has always had the philosophy that even though much of what we do is basic science, if we find something that could be translated, we should make every effort to do that,” says Dr. Miller.
Within the three-year grant, which ended February 2016, their research led to a number of notable findings from both their animal and human studies, resulting in a total of 13 publications in several high-impact journals, including Cell Stem Cell, and Neuron.
The research continues to make an impact: currently, three clinical trials have stemmed from the original discovery in Dr. Miller’s lab, including one exploring the benefits of metformin on repairing brain injuries in children caused by tumour irradiation. The findings were published in Nature Medicine in July 2020, with two of the Brain Canada grant co investigators, Drs. Donald Mabbott and Cindi Morshead, as senior authors.
“Metformin, in the short-term at least, looked like it was able to enhance some measures of brain repair, and even potentially improvement on certain types of cognitive tasks,” says Dr. Miller. While this was a pilot trial, it is providing the basis for a larger multi-centre clinical trial that is currently being organized.
Another pilot trial, led by Dr. Ann Yeh, is also looking at whether metformin can help repair damaged white matter in the brains of children with a multiple sclerosis-like inflammatory disorder.
For Dr. Miller, these exceptional results further the case for the “one brain” approach to neurological disorders, mental illness, and brain injury, meaning that every discovery has the potential to have an impact on multiple brain disorders, and to further our understanding of brain functioning—an approach that has underpinned Brain Canada’s support of collaborative research teams for more than two decades.