Understanding the Mechanism of Action of Bruton’s Tyrosine Kinase Inhibitors (BTKi) Using an Animal Model of MS

Start Term
End Term
Funding Amount
$300,000
Affiliation(s)
University of Toronto
Geographic Region(s) / Province(s)
Ontario
Researcher(s)
Dr. Jennifer Gommerman
Research Priorities
Progressive MS
Impact Goal(s)
Advance Treatment and Care

Summary:  

  • Injury to the brain’s grey matter is frequently observed in people with progressive MS. Preliminary studies from Dr. Jennifer Gommerman’s laboratory found that Bruton’s Tyrosine Kinase inhibitors or BTKi are effective in preventing grey matter injury in an animal model of MS.  

  • In this study, the researchers will investigate the mechanisms by which BTKi delay disease progression in MS by preserving grey matter volume. They will also determine if specific pathways, genes or proteins within the brain are altered following BTKi treatment, and whether these targets are responsive to alternative therapies that have fewer side effects.  

  • The findings of this study will provide new insights into the mechanisms of action of BTKi and will support the development of more targeted and effective therapies for progressive MS.  

Project Description:  

Injury to the grey matter of the brain, including demyelination and damage to nerve cells, is a hallmark of progressive MS. Initial studies from Dr. Jennifer Gommerman’s laboratory found that when animal models of MS were treated with BTKi – a newer class of drugs that can reach the brain and target inflammation in the central nervous system – there was a reduction in grey matter pathology. The team also reported that the beneficial effects occurred by blocking specific signaling pathways along with production of a molecule called CXCL13. 

In the present study, Dr. Gommerman and team have developed a specialized animal model of MS where injury to cortical grey matter is caused by an immune attack. The researchers will use this model to: 

  1. Understand the mechanisms in which BTKi preserve grey matter volume in mice with MS-like disease.
  2. Identify potential changes in brain pathways, genes and proteins as a result of BTKi treatment.
  3. Determine if the genes and proteins that are responsive to BTKi can be targeted by alternative therapies with minimal side effects.

Potential Impact: The findings from this research will provide new insights into the mechanisms of action of BTK inhibitors and potentially identify new targets for intervention for progressive forms of MS. 

Project Status: In Progress