Characterizing a New Mouse Model for Progressive MS

Start Term
End Term
Funding Amount
$299,990
Affiliation(s)
University of Calgary
Geographic Region(s) / Province(s)
Alberta
Researcher(s)
Dr. Peter Stys
Research Priorities
Progressive MS
Impact Goal(s)
Understand and Halt Disease Progression

Summary:  

  • A major obstacle in understanding and developing treatments for progressive MS is the lack of a suitable animal model that accurately reflects the human condition.  

  • Dr. Peter Stys and team will characterize a new mouse model called ND4, which closely mimics the features of progressive MS in humans. They will also use ND4 mice to test the efficacy of a promising drug candidate that was previously shown to reduce neurodegeneration and inflammation in pre-clinical models.  

  • This research has the potential to generate a more useable and realistic model for studying disease progression in MS and pave the way for the development of novel therapeutic strategies for treating progressive MS.  


Project Description:  

A better understanding of progressive MS is of critical importance because most people with MS will eventually transition to this phase where permanent disability accumulates, and current available treatments are not effective at targeting MS progression. A major obstacle in understanding and developing treatments for progressive MS is the lack of a suitable animal model that accurately reflects the human condition. 

Dr. Peter Stys and his team will study a newly developed mouse model, known as DM-20 over-expressing or ND4 mouse, which shares key features with human progressive MS in terms of neuropathology, MRI abnormalities, and biochemical changes. The researchers hypothesize that the brains of people with MS have widespread protein misfolding, a process in which proteins lose their normal shape and function leading to eventual degeneration of the MS brain. The ND4 mice exhibit a similar misfolded protein pathology and could present as a more realistic model for studying progressive MS. 

Furthermore, the researchers will use ND4 mice to test a new small molecule drug candidate designed to block a specific biochemical modification to proteins (hypercitrullination) that likely triggers inflammation and myelin loss in MS. This drug candidate was already shown to be effective in reducing degeneration and inflammation in related mouse models and is currently in phase 1 of human clinical trials. 

Potential Impact: This research has the potential to generate a more useable and realistic model for studying disease progression in MS and pave the way for the development of novel therapeutic strategies for treating progressive MS.

Project Status: In Progress