Mechanisms of Delayed White Matter Degeneration in a Mouse Model of Progressive MS

Start Term
End Term
Funding Amount
$299,344
Affiliation(s)
University of Calgary
Geographic Region(s) / Province(s)
Alberta
Researcher(s)
Dr. Peter Stys
Impact Goal(s)
Understand and Halt Disease Progression

Summary:

  • This research will develop a cuprizone mouse model that recapitulates many aspects of progressive MS.
  • Dr. Stys and team will apply advanced microscopic analysis, brain MRI and behavioural testing to better understand the tissue-level changes and mechanisms associated with degeneration.
  • Results from this project will shed important light on the degenerative aspects of MS, paving the way for next-generation therapies targeting the progressive disabling stage of the disease.

Project Description:

MS is unique among neurological conditions as it exhibits both a prominent relapsing inflammatory phase early in the disease course that is often followed by disability progression and a progressive phase. Although a number of effective drugs are available for relapsing-remitting MS, there are limited options for patients in the progressive stages. A major reason is the lack of knowledge about the basic biology of what drives the progressive stage of the disease. This research will develop a mouse model that duplicates many aspects of progressive MS. Cuprizone, a substance known to bind copper in food, will be administered to mice, causing loss of myelin in the brain within a few weeks. Withdrawal of this agent allows the mouse brain to fully recover, however after several months, without re-exposure to cuprizone, the mouse brain starts to degenerate in many ways similar to the progressive MS brain. This late spontaneous phase will be the subject of this proposal. Dr. Stys and team will perform microscopic analysis of brain tissues from cuprizone exposed mice, live mouse scanning by MRI and behavioral testing, to better understand the time course and tissue-level changes associated with the degeneration. They will also apply advanced microscopic methods to detect accumulation of misfolded proteins in the mouse brain, such as amyloid, which could cause the delayed toxicity and degeneration in this animal model.

Potential Impact:

Results from this project will shed important light on the degenerative aspects of MS, paving the way for next-generation therapies targeting the progressive stage of the disease.

Project Status: In progress