Cindi Morshead, University of Toronto, Toronto, Canada

Exploring the effect of metformin on endogenous neural stem cells

Funded in: 2020, 2021, 2022

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Problem: Neural stem cells in the spinal cord can generate lost cells
Target: Activate resident neural stem cells by using the drug metformin
Goal: Establish novel, clinically relevant strategies via the effect of metformin

The spinal cord contains a small population of stem cells. These cells have the potential to expand in number and make the neural cells that are lost after spinal cord injury.  However, we need a strategy to activate these resident stem cells to promote repair and recovery from spinal cord injury.
Metformin, a drug commonly used to treat type 2 diabetes, has the ability to activate resident neural stem cells in the brain, leading to increased proliferation and maturation of new cells and improved function following brain injury. Metformin’s potential has yet been tested in the spinal cord. Exciting preliminary results from the research group show that metformin is able to activate stem cells in the spinal cord leading to an increase in their number and the generation of mature cell types lost to injury.  Most important, metformin leads to improved functional outcomes.  Now, the researchers aim to build on these findings and fully explore the ability of metformin to promote neurorepair and recovery.  
These studies will evaluate the cellular basis for the improved outcomes following metformin treatment and determine the therapeutic window of efficacy for the treatment. The Morshead group will take advantage of pre-clinical animal models that permit to delineate the cellular response and identify which cells are necessary and/or sufficient for the metformin mediated recovery.  This will help to identify potential targets for novel therapeutic interventions to treat spinal cord injury.