Gait parameters as predictors of functional recovery in a mouse model of MS

Principal Investigator: Dr. George Robertson

Affiliation: Dalhousie University

Term: April 1, 2017 – March 31, 2020

Funding: $300,185

Keywords: Walking deficits, gait analysis, Pioglitazone

Summary:

  • At least nine different types of drugs have been shown to protect myelin and reduce paralysis in mouse models mimicking multiple sclerosis (MS), and might have beneficial effects in individuals with MS. However, a large number of individuals with MS must be tested with these drugs for years to confirm they safely and effectively improve MS.
  • There is an unmet need to develop a technique which will be able to identify the best drug candidates in in mouse models of MS, that could exert beneficial properties in people with MS.
  • The research team will:
    • Use a technique called kinematic gait analysis which measures hip, knee and ankle movements in animals with MS to determine drugs that will potentially have the most benefit in people with MS.

Project Description:

At least nine different types of drugs have been shown to stimulate remyelination and reduce motor deficits in mouse models of MS-like disease. Dr. George Robertson’s aims to determine which of the nine drugs are most likely to improve mobility of MS patients by stimulating myelin repair. To evaluate this, the research team will use a method called kinematic gait analyses which can be performed using sensitive measurements of hip, knee and ankle movements on mice with MS-like disease walking on a treadmill. For example, improved ankle movement during walking is closely linked with increased myelin repair. These sophisticated methods for measuring movement have often been used to describe walking impairments for people with MS. This technique will be used to determine which of the 9 drugs best improves the leg movements in animal models of MS. In the past year, Dr. Robertson’s team has discovered one of the nine drugs, called pioglitazone, decreases paralysis and myelin loss in the spinal cords of mice with MS-like disease. Using kinematic gait analysis, the research team also discovered that pioglitazone also maintained normal movements of the hip, knee and ankle joints for 44 days. These results support the findings of small clinical studies that suggest pioglitazone may reduce the progressive loss of mobility in MS by decreasing inflammation and myelin damage.

Potential Impact: Establish a sensitive analytic tool of movement analysis for selecting the most promising therapeutic compounds for human testing that will improve the mobility in individuals with MS.

Project Status: In Progress

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