Project Description

Challenge

One of the primary treatments for cerebral palsy (CP) is constraint-induced movement therapy (CIMT). CIMT immobilizes the stronger limb, forcing the patient to use – and hopefully improve function – in the weaker one. Our researcher team (led by Dr. Derek van der Kooy, University of Toronto) investigated why CIMT works. They believed it would improve outcomes by activating neural stem and progenitor cells in the brain. By gaining a better understanding of the mechanisms through which CIMT enhances motor function, researchers could improve its therapeutic efficacy. This understanding can potentially provide the bases for better CP treatments in the future.

Project Summary

Neural stem and progenitor cells are thought to produce new neurons and glial cells that could potentially regenerate the brain. The team has shown that CIMT in a mouse model of CP stimulates these cells and causes observable behavioural recovery when used with effects with the transplantation of neural precursor cells. In a second project, researchers removed the neural stem and progenitor cells in the brains of mice. They did this to determine whether or not cell activation is required for the improvements seen in behaviour after CIMT.

The group also explored different ways of increasing activation of the stem and progenitor cells to encourage brain regeneration. For example, the team demonstrated that drugs such as Metformin –enhances motor recovery and reduces cognitive impairments in a mouse model that mimics the motor deficits found in people with CP.

Result

The researchers generated enriched populations of human forebrain neural precursors that are biased towards neuron and oligodendrocyte fates. They have done this to help test which types of neural precursors are most important for behavioural recovery in mouse models of CP.

Funding

Kids Brain Health Network – $320,001

Partners – $618,000

Team

Principal Investigator

Derek van der Kooy

Co-principal Investigators

Cindi Morshead, University of Toronto
Michael Fehlings, Toronto Western Hospital
Andras Nagy, University of Toronto
Alen Peterson, McGill University

Collaborators

Darcy Fehlings, Holland-Bloorview Kids Rehabilitation Hospital
Adam Kirton, University of Calgary